Nutrition for Disorders of the Liver, Gallbladder, and Pancreas

Each year, millions of Americans are diagnosed with digestive disorders, ranging from the occasional upset stomach to the more life-threatening colorectal cancer. They encompass disorders of the gastrointestinal tract, as well as the liver, gallbladder, and pancreas.

The Liver: Anatomy and Functions

Anatomy of the liver:

The liver is located in the upper right-hand portion of the abdominal cavity, beneath the diaphragm, and on top of the stomach, right kidney, and intestines. Shaped like a cone, the liver is a dark reddish-brown organ that weighs about 3 pounds.

There are two distinct sources that supply blood to the liver, including the following:

oxygenated blood flows in from the hepatic artery

nutrient-rich blood flows in from the hepatic portal vein

The liver holds about one pint (13 percent) of the body's blood supply at any given moment. The liver consists of two main lobes, both of which are made up of thousands of lobules. These lobules are connected to small ducts that connect with larger ducts to ultimately form the hepatic duct. The hepatic duct transports the bile produced by the liver cells to the gallbladder and duodenum (the first part of the small intestine).

Did you know?

The liver can lose three-quarters of its cells before it stops functioning.

In addition, the liver is the only organ in the body that can regenerate itself.

Functions of the liver:

The liver regulates most chemical levels in the blood and excretes a product called bile, which helps carry away waste products from the liver. All the blood leaving the stomach and intestines passes through the liver. The liver processes this blood and breaks down the nutrients and drugs into forms that are easier to use for the rest of the body. More than 500 vital functions have been identified with the liver. Some of the more well-known functions include the following:

production of bile, which helps carry away waste and break down fats in the small intestine during digestion

production of certain proteins for blood plasma

production of cholesterol and special proteins to help carry fats through the body

conversion of excess glucose into glycogen for storage (glycogen can later be converted back to glucose for energy)

regulation of blood levels of amino acids, which form the building blocks of proteins

processing of hemoglobin for use of its iron content (the liver stores iron)

conversion of poisonous ammonia to urea (urea is an end product of protein metabolism and is excreted in the urine)

clearing the blood of drugs and other poisonous substances

regulating blood clotting

resisting infections by producing immune factors and removing bacteria from the bloodstream

When the liver has broken down harmful substances, its by-products are excreted into the bile or blood. Bile by-products enter the intestine and ultimately leave the body in the form of feces. Blood by-products are filtered out by the kidneys, and leave the body in the form of urine.

Disorders of the Liver

There are many disorders of the liver that require clinical care by a physician or other healthcare professional. Listed in the directory below are some, for which we have provided a brief overview.

If you cannot find the information in which you are interested, please visit the Liver Disorders Online Resources page in this Web site for an Internet/World Wide Web address that may contain additional information on that topic.

About 95 million persons are affected by all digestive problems. Digestive disorders account for 35 million physician office visits per year.

Most digestive diseases are very complex, with subtle symptoms, and the causes of many remain unknown. They may be inherited, or develop from multiple factors such as stress, fatigue, diet, or smoking. Abusing alcohol imposes the greatest risk for digestive diseases.

Reaching a diagnosis requires a thorough and accurate medical history and physical examination. Some patients may need to undergo more extensive diagnostic evaluations, including lab tests, endoscopic procedures, and imaging techniques. Physicians who specialize in the treatment of digestive problems are called gastroenterologists.

 Liver, Biliary, and Pancreatic Disorders

More than 25 million US adults suffer from liver, bile duct, or gallbladder diseases, according to the American Liver Foundation.

The liver is the largest organ in the human body. It is also one of the most important ones. The biliary system consists of the bile ducts, gallbladder, and pancreas - all closely associated with the functioning of the liver.

Some liver, biliary, and pancreatic diseases are congenital (present at birth). Others can be prevented. In any case, whether these diseases are congenital, injury-related, viral-induced, or alcohol-induced, they can be devastating to a person's health and require medical care.

Alcohol-Induced Liver Disease

Did you know?

Women are more prone to liver damage from drinking alcohol than men.

What is alcohol-induced liver disease?

Alcohol-induced liver disease, as the name implies, is caused by excessive consumption of alcohol and is a common, but preventable, disease.

There are three primary types of alcohol-induced liver disease, including the following:

fatty liver Fatty liver is excessive accumulation of fat inside the liver cells. Fatty liver is the most common alcohol-induced liver disorder. The liver is enlarged, causing upper abdominal discomfort on the right side.

alcoholic hepatitis Alcoholic hepatitis is an acute inflammation of the liver, accompanied by the destruction of individual liver cells and scarring. Symptoms may include fever, jaundice, an increased white blood cell count, an enlarged, tender liver, and spider-like veins in the skin.

alcoholic cirrhosis Alcoholic cirrhosis is the destruction of normal liver tissue, leaving non-functioning scar tissue. Symptoms may include those of alcoholic hepatitis, in addition to portal hypertension, enlarged spleen, ascites, kidney failure, confusion, or liver cancer.

What are the symptoms of alcohol-induced liver disease?

Symptoms of alcohol-induced liver disease depend on how much and how long a person has been drinking alcohol. The following are the most common symptoms of alcohol-induced liver disease. However, each individual may experience symptoms differently. Symptoms may include:

enlarged liver

fever

jaundice - yellowing of the skin and eyes.

increased white blood cell count

spider-like veins in the skin

portal hypertension

enlarged spleen

ascites - fluid build-up in the abdominal cavity.

kidney failure

confusion

The symptoms of alcohol-induced liver disease may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

How is alcohol-induced liver disease diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for alcohol-induced liver disease may include the following:

laboratory tests

liver function tests - a series of special blood tests that can determine if the liver is functioning properly.

liver biopsy - a procedure in which tissue samples from the liver are removed (with a needle or during surgery) from the body for examination under a microscope.

Treatment for alcohol-induced liver disease:

Specific treatment for alcohol-induced liver disease will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

your tolerance for specific medications, procedures, or therapies

expectations for the course of the disease

your opinion or preference

The goal of treatment is to restore some or all normal functioning to the liver. Treatment usually begins with abstinence from alcohol. The liver has great restorative power and is often able to repair some of the damage caused by alcohol. In most cases, the only damage it cannot reverse is scarring from cirrhosis.

Chronic Liver Disease /Cirrhosis

What is chronic liver disease?

Chronic liver disease is marked by the gradual destruction of liver tissue over time. Several liver diseases fall under this category, including the following:

cirrhosis of the liver

fibrosis of the liver

What is cirrhosis of the liver?

Cirrhosis is the 12th leading cause of death in the United States, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Because of chronic damage to the liver, scar tissue slowly replaces normal functioning liver tissue, progressively diminishing blood flow through the liver. As the normal liver tissue is lost, nutrients, hormones, drugs, and poisons are not processed effectively by the liver. In addition, protein production and other substances produced by the liver are inhibited.

What are the symptoms of cirrhosis?

Symptoms of cirrhosis vary, depending on severity of the condition. Mild cirrhosis may not exhibit any symptoms at all. The following are the most common symptoms of cirrhosis. However, each individual may experience symptoms differently. Symptoms may include:

abnormal nerve function

ascites - fluid build-up in the abdominal cavity.

breast enlargement in men

coughing up or vomiting blood

curling of fingers (Dupuytren's contracture of the palms)

gallstones

hair loss

itching

jaundice - yellowing of the skin and eyes.

kidney failure

liver encephalopathy

muscle loss

poor appetite

portal hypertension

redness of palms

salivary gland enlargement in cheeks

shrinking of testes

spider-like veins in the skin

weakness

weight loss

The symptoms of cirrhosis may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

What causes cirrhosis?

The most common cause of cirrhosis is alcohol abuse. Other causes include the following:

hepatitis and other viruses

use of certain drugs

chemical exposure

bile duct obstruction

autoimmune diseases

obstruction of outflow of blood from the liver (i.e., Budd-Chiari syndrome)

heart and blood vessel disturbances

alpha₁-antitrypsin deficiency

high blood galactose levels

high blood tyrosine levels at birth

glycogen storage disease

cystic fibrosis

diabetes

malnutrition

hereditary accumulation of too much copper (Wilson's Disease) or iron (hemochromatosis)

How is cirrhosis diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for cirrhosis may include the following:

laboratory tests

liver function tests - a series of special blood tests that can determine if the liver is functioning properly.

liver biopsy - a procedure in which tissue samples from the liver are removed (with a needle or during surgery) from the body for examination under a microscope.

cholangiography - x-ray examination of the bile ducts using an intravenous (IV) dye (contrast).

computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure using a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

ultrasound (Also called sonography.) - a diagnostic imaging technique, which uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs of the abdomen such as the liver, spleen, and kidneys and to assess blood flow through various vessels.

Treatment for cirrhosis:

Specific treatment for cirrhosis will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

your tolerance for specific medications, procedures, or therapies

expectations for the course of the disease

your opinion or preference

Cirrhosis is a progressive liver disease, and damage sustained to the liver is irreversible. However, with proper nutrition, avoidance of certain toxins (such as alcohol), vitamin supplementation, and management of cirrhosis complications, further liver damage can often be delayed or stopped. In severe cases of cirrhosis, liver transplantation may be considered.

What is fibrosis?

Fibrosis is the growth of scar tissue due to infection, inflammation, injury, or even healing. The overgrowth of scar tissue can occur in almost any organ. Fibrosis in the liver can inhibit the organ's proper functioning. Liver fibrosis is usually the result of cirrhosis.

Congenital Liver Defects

What are congenital liver defects?

Defects of the liver at birth usually affect the bile ducts. Though rare, some congenital liver defects include the following:

biliary atresia - a condition in which the bile ducts are absent or have developed abnormally.

choledochal cyst - a malformation of the hepatic duct that can obstruct flow of bile in infants.

What are the indicators that a congenital liver defect may be present?

Congenital liver defects that affect the flow of bile share some common symptoms. The following are the most common symptoms of congenital liver defect. However, each individual may experience symptoms differently. Symptoms may include:

jaundice - yellowing of the skin and eyes.

dark urine

pale stool

The symptoms of congenital liver defects may resemble other medical conditions or problems. Always consult your child's physician for a diagnosis.

How are congenital liver defects diagnosed?

Congenital liver defects that affect the flow of bile are usually diagnosed at birth or shortly afterward. In addition to a complete medical history and physical examination, diagnostic procedures for a congenital liver defect may include the following:

laboratory tests

liver function tests - a series of special blood tests that can determine if the liver is functioning properly.

liver biopsy - a procedure in which tissue samples from the liver are removed (with a needle or during surgery) from the body for examination under a microscope.

Treatment for congenital liver defects:

Specific treatment for congenital liver defects will be determined by your child's physician based on:

your child's age, overall health, and medical history

extent of the disease

your child's tolerance for specific medications, procedures, or therapies

expectations for the course of the disease

your opinion or preference

Treatment may include surgery to reconstruct or bypass the bile ducts. Sometimes, a liver transplant may be necessary.

Hepatitis

There are several types of hepatitis that require clinical care by a physician or other healthcare professional. Listed in the directory below are some, for which we have provided a brief overview.

If you cannot find the information in which you are interested, please visit the Liver Disorders Online Resources page in this Web site for an Internet/World Wide Web address that may contain additional information on that topic.

Hepatitis In-Depth Report

In-Depth From A.D.A.M. Background

Hepatitis is a disorder in which viruses or other mechanisms produce inflammation in liver cells, resulting in their injury or destruction. The liver is the largest organ in the body, occupying the entire upper right quadrant of the abdomen. It performs over 500 vital functions including:

· The liver processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

· The liver manufactures bile, the greenish fluid stored in the gallbladder that helps digest fats.

· One of the liver's major contributions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

· Old red blood cells are removed from the blood by the liver and spleen, and the iron contained in them is recycled to the bone marrow to make new red blood cells.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

Damage to the liver can impair these and many other processes. Hepatitis varies in severity from a self-limited condition with total recovery to a life-threatening or life-long disease. It can occur from many different causes:

· In the most common hepatitis cases (viral hepatitis), specific viruses incite the immune system to fight off infections. Specific immune factors become over-produced that cause injury.

· Hepatitis can also result from an autoimmune condition, in which abnormal immune factors attack the body's own liver cells.

· Inflammation of the liver can also occur from medical problems, drugs, alcoholism, chemicals, and environmental toxins.

No matter what the cause of hepatitis, it can take either an acute (short term) or chronic (long term) form. In some cases, acute hepatitis develops into a chronic condition, but chronic hepatitis can also occur on its own. Although chronic hepatitis is generally the more serious condition, patients having either condition can experience varying degrees of severity.

Acute Hepatitis. Acute hepatitis can begin suddenly or gradually, but it has a limited course and rarely lasts beyond 1 or 2 months. Usually, there is only spotty liver cell damage and evidence of immune system activity. Rarely, acute hepatitis can cause severe, even life-threatening, liver damage.

Chronic Hepatitis. The chronic forms of hepatitis last for prolonged periods. Doctors usually categorize chronic hepatitis by indications of severity:

· Chronic persistent hepatitis is usually mild and nonprogressive or slowly progressive, causing limited damage to the liver.

· Chronic active hepatitis involves extensive liver damage and cell injury beyond the portal tract.

Viral Hepatitis

Most cases of hepatitis are caused by viruses that infect liver cells and begin replicating. They are defined by the letters A through G:

· Hepatitis A, B, and C are the most common viral forms of hepatitis. Investigators are still looking for additional viruses that may be implicated in hepatitis unexplained by the current known viruses.

· Other hepatitis viruses include hepatitis E and hepatitis G. Like hepatitis A, hepatitis E is caused by contact with contaminated food or water. It is not serious except in pregnant women, when it can be life threatening. Hepatitis G is always chronic and most likely has the same modes of transmission as hepatitis C. It does not appear to have serious effects.

Scientists do not know exactly how these viruses actually cause hepatitis (inflammation in the liver). As the virus reproduces in the liver, several proteins and enzymes, including many that attach to the surface of the viral protein, are also produced. Some of these may be directly responsible for liver damage. Researchers are investigating elevated levels of specific immune factors, including T cell sub-types in the liver of hepatitis C and B patients. T cells are important infection fighters in the immune system that in some cases release powerful inflammatory substances (tumor necrosis factor and interferon gamma) that can cause considerable damage leading to hepatitis B or C.

Autoimmune Chronic Hepatitis

Autoimmune chronic hepatitis accounts for about 20% of all chronic hepatitis cases. Like other autoimmune disorders, this condition develops because a genetically defective immune system attacks the body's own cells and organs (in this case the liver). The attack is triggered by an environmental factor, probably a virus. Suspects include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in susceptible individuals. In about 30% of cases, autoimmune hepatitis is associated with other disorders that involve autoimmune attacks on other parts of the body.

Hepatitis Caused by Alcohol and Drugs

Alcohol. About 10 - 35% of heavy drinkers develop alcoholic hepatitis. In the body, alcohol breaks down into various chemicals, some of which are very toxic to the liver. After years of drinking, liver damage can be very severe, leading to cirrhosis in about 10 - 20% of cases. Although heavy drinking itself is the major risk factor for alcoholic hepatitis, genetic factors may play a role in increasing a person's risk for alcoholic hepatitis. Women who abuse alcohol are at higher risk for alcoholic hepatitis and cirrhosis than are men who drink heavily. High-fat diets may also increase the risk in heavy drinkers.

Drugs. Because the liver plays such a major role in metabolizing drugs, hundreds of medications can cause reactions that are similar to those of acute viral hepatitis. Symptoms can appear anywhere from 2 weeks to 6 months after starting drug treatment. In most cases, they disappear when the drug is withdrawn, but in rare circumstances they may progress to serious liver disease. Drugs most noted for liver interactions include halothane, isoniazid, methyldopa, phenytoin, valproic acid, and the sulfonamide drugs. Very high doses of acetaminophen (Tylenol) have been known to cause severe liver damage and even death, particularly when used with alcohol.

Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) affects between 10 - 24% of the population. It covers several conditions, including nonalcoholic steatohepatitis (NASH). NAFLD has features similar to alcoholic hepatitis, particularly a fatty liver, but it occurs in individuals who drink little or no alcohol. Severe obesity and diabetes are the major risk factors for NAFLD as well as complications from NAFLD. NAFLD is usually benign and very slowly progressive. In certain patients, however, it can lead to cirrhosis, liver failure, or liver cancer. <!--[For more information, see In-Depth Report #75: Cirrhosis.]-->

In-Depth From A.D.A.M. Diagnosis

In people suspected of having or carrying viral hepatitis, doctors will measure certain substances in the blood.

· Bilirubin. Bilirubin is one of the most important factors indicative of hepatitis. It is a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise. (High levels of bilirubin cause the yellowish skin tone, known as jaundice.)

· Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Blood is drawn from a vein (venipuncture), usually from the inside of the elbow or the back of the hand. A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe. Preparation may vary depending on the specific test.

General Tests to Determine Causes of Viral Hepatitis

Radioimmunoassays. To identify the particular virus causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous and which can be targeted by antibodies.) Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

· There may not be sufficient numbers of antibodies to be detectable by blood tests for up to weeks or months after hepatitis develops. Blood tests that are taken too early may miss these signs of infection.

· Antibodies also linger after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. PCR is able to make multiple copies of the virus’ genetic material to the point where it is detectable.

Liver Biopsies

A liver biopsy may be performed for acute viral hepatitis caught in a late stage or for severe cases of chronic hepatitis. No laboratory tests for enzyme or viral levels can truly determine the actual damage to the liver. A biopsy helps determine treatment possibilities, the extent of damage, and the long-term outlook.

The biopsy requires abdominal surgery, most often laparoscopy. This procedure takes about an hour. It requires general anesthesia and involves the following steps:

· The surgeon makes one or more small incisions (about 0.5 - 1.0 inch) in the abdomen.

· Carbon dioxide or nitrous oxide is delivered through the incision to inflate the abdomen so that the involved area is visible.

· The surgeon inserts a thin tube, called a laparoscope, which contains a tiny camera. Surgical instruments are also inserted through the incision to remove the liver tissue for biopsy.

A liver biopsy is not a routine procedure, but is performed when it is necessary to determine the presence of liver disease and to look for malignancy, cysts, parasites, or other pathology. The actual procedure is only slightly uncomfortable. Most of the discomfort arises from being required to lie still for several hours afterwards to prevent bleeding from the biopsy site.

A less invasive procedure, called a minilaparoscopy, uses a smaller scope and may prove to reduce the time of the procedure.

Screening for Liver Cancer

Patients with cirrhosis are usually screened for liver cancer using tests for a substance called alpha-fetoprotein (AFP) and ultrasound. It is not known, however, if such screening has much impact on survival, since it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

In-Depth From A.D.A.M. Hepatitis A

About a third of the U.S. population has antibodies to hepatitis A, indicating previous infection by the virus. The hepatitis A virus infects up to 200,000 Americans every year and causes symptoms in about 134,000 of them. Almost 30% are children under age 15.

Hepatitis A (formerly called infectious hepatitis) is excreted in feces and transmitted by contaminated food and water. Eating shellfish taken from sewage-contaminated water is a common means of contracting hepatitis A. Infected people can transmit it to others if they do not take strict sanitary precautions. Hepatitis A is infectious for 2 - 4 weeks before symptoms develop and for a few days afterward.

People at risk for passing the infection along or being infected include:

· International travelers. Hepatitis A is the hepatitis strain people are most likely to encounter in the course of international travel. In fact, in spite of the availability of a vaccine, the increase in travel to underdeveloped countries has kept the incidence of hepatitis A steady in Western nations. The incidence may even be increasing.

· Day care employees and children. It is estimated that between 11 - 16% of hepatitis A cases occur among day care employees and children who attend day care. The risk for children attending day care is very low, however, if hygienic precautions are used, particularly when changing babies and handling diapers.

· Sexually active homosexual men.

· Intravenous drug users.

· Health care, food industry, and sewage workers.

A fly may act as a mechanical vector of diseases such as hepatitis A, which means the fly carries the infective organism on its feet or mouth parts and contaminates food or water which a person then consumes. A biological vector actually develops an infective organism in its body and passes it along to its host, usually through its saliva. A fly can be a biological vector, as in the transmission of leishmaniasis by the sandfly.

Symptoms of Acute Hepatitis

Symptoms of acute viral hepatitis may begin suddenly or develop gradually. They may be so mild that patients mistake the disease for the flu. They include:

· Nearly all patients experience some fatigue and often have mild fever.

· Gastrointestinal problems are very common, including nausea, vomiting, a general feeling of discomfort in the abdomen, or a sharper pain that may occur in the upper right area of the abdomen. This pain tends to increase during jerking movements, such as climbing stairs or riding on a bumpy road.

· Gastrointestinal problems can also lead to loss of appetite, weight loss, and dehydration.

· After about 2 weeks, dark urine and jaundice (a yellowish color in the skin and whites of the eyes) develops in some, but not all, patients. (Children tend not to develop jaundice.)

· About half of all patients have light colored stools, muscle pain, drowsiness, irritability, and itching, usually mild.

· Diarrhea and joint aches occur in about a quarter of patients.

· The liver may be tender and enlarged, and most people have mild anemia.

· In about 10% of patients, the spleen is enlarged.

Preventing Hepatitis A Infections When Traveling to High-Risk Countries

Travelers should take the following precautions:

· Get vaccinated against hepatitis A and possibly B if traveling for long periods of time to countries where epidemics occur.

· Use only carbonated bottled water for brushing teeth and drinking. (Remember that ice cubes can carry infection.) Boiling water is the best method for eliminating infectious organisms. Bringing the water to a good boil for at least a minute generally renders it safe to drink.

· Heated food should be hot to the touch and eaten promptly.

· Don’t buy food from street vendors.

· Beware of sliced fruit that may have been washed in contaminated water. Travelers themselves should peel all fresh fruits and vegetables.

· Avoid dairy products.

· Avoid raw or undercooked meat and fish.

Vaccinations for Hepatitis A

Two vaccines (Havrix, Vaqta) are now available, both very safe and effective for preventing hepatitis A (HAV). They can be given along with immune globulin and other vaccines. A combination Hep A - Hep B vaccine (Twinrix) that contains both Havrix and Engerix-B (a hepatitis B vaccine) is also available.

Immunization is a process to initiate or augment resistance to an infectious disease. The goal of immunization is to prevent, and in some cases eradicate, potentially serious, life-threatening diseases. Candidates for HAV Vaccinations. Vaccinations for hepatitis A are recommended for:

· Children age 12 - 23 months (the U.S. Centers for Disease Control and Prevention recommends that children receive the first dose of the hepatitis A vaccine when they are 12 months old, and a second dose 6 months later). Hepatitis A used to affect mostly children, but now occurs mostly in adults.

· Travelers to developing countries. (Travelers should also receive immune globulin if they are visiting high-risk areas within 4 weeks of the vaccination.)

· Sexually active homosexual men

· Illegal drug users, especially those who inject drugs

· Health care workers

· People with chronic liver disease

· People with hemophilia or other blood-clotting disorders

Side Effects. Although there are few side effects, allergic responses from the vaccination can occur. Hair loss has been reported in very few people after a second administration. There may be pain at the injection site. (Havrix causes more pain at the injection site than Vaqta.)

Symptoms of Hepatitis A

Symptoms are usually mild, especially in children, and generally appear between 2 - 6 weeks after exposure to the virus. Adult patients are more likely to have fever, jaundice, and itching that can last up to several months.

General Outlook for People Infected with Hepatitis A

Hepatitis A is the least serious of the common hepatitis viruses. It does not directly kill liver cells, and there is no risk for a chronic form. Severe (fulminant) hepatitis is the only major concern, but even if it develops, it is almost always less dangerous than with other viral types. Only 1 in a 1,000 patients is at risk for death from this complication. If hepatitis A infection occurs in patients with hepatitis C, however, superinfections can occur, even without cirrhosis, leading to a life-threatening form of fulminant hepatitis. (Infection of patients with hepatitis B who do not have cirrhosis does not appear to be as dangerous.)

Specific Tests for Hepatitis A

Radioimmunoassays are generally used to identify IgM antibodies, first produced to fight hepatitis A. They appear early in the course of the disease and usually can be identified as soon as symptoms appear. IgM antibodies disappear during recovery, but those known as IgG antibodies persist, and their presence can be used to indicate a previous infection.

Treatments and Measures to Prevent Transmission of Hepatitis A

The primary goals for managing acute viral hepatitis are to provide adequate nutrition, to prevent additional damage to the liver, and to prevent transmission to others.

Precautions for Preventing Transmission of Hepatitis A. Because hepatitis A and hepatitis E are usually passed through contaminated food, people with these viruses should not prepare food for others. Unfortunately, these viruses are most contagious before symptoms appear.

· Using hot water when cleaning utensils or clothing is essential. Heating a contaminated article for 1 minute kills the virus. Simple household bleach is effective for disinfecting hard surfaces. Sterilizing is not necessary. Still, even with strong precautions, utensils used by the patient for eating and cooking should be kept separate from those used by others.

· Abstain from sexual activity or take strict precautions.

· Abstain from alcohol. Moderate drinking after recovery is not harmful for most people.

In-Depth From A.D.A.M. Hepatitis B and D

Hepatitis B and D were formerly called serum hepatitis. Hepatitis B is mainly transmitted through blood transfusions, contaminated needles, and sexual contact. Blood screening has reduced the risk from transfusions. It can also be passed from cuts, scrapes, and other breaks in the skin. Hepatitis D virus can replicate only by attaching to hepatitis B and therefore cannot exist without the B virus being present.

Risk Factors for Hepatitis B. About 1.2 million Americans are chronically infected with hepatitits B and between 20 - 30% acquired the infection when they were children. Men are at higher risk than women. Among ethnic groups living in the United States, Asians are at highest risk, due to the high rate of hepatitits B in Asian countries. Fortunately, in the US the number of new infections has declined dramatically -- by 67% between 1990 and 2002. In 2003, 7,526 cases were reported compared to over 20,000 in 1990. The greatest decrease has occurred in children. Among young adults and people living in the Northeast, however, the incidence has increased since 1999. This may indicate that sexual activity is an important route for viral transmission and that the protective effect of the vaccine has not yet reached older, high-risk groups. Also, as with hepatitis A, the increase in travelers to underdeveloped nations may be responsible for the steady rate.

Hepatitits B is far more common overseas and about 600,000 people die each year from conditions, such as liver cancer or cirrhosis, that are related to chronic hepatitis B. Nearly 70% of these infections were acquired during infancy or early childhood.

People at risk include:

· Drug users who share needles.

· Children of infected mothers. Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing hepatitits B before age 5. Children are more likely than adults to become chronic carriers, although between 6 - 12% of children spontaneously recover each year.

· People with multiple sex partners or other high-risk sexual behavior.

· Hospital workers and others exposed to blood products. Contaminated medical instruments, including fingerstick devices used for more than one individual, have been known to transmit the virus.

· Staff members and clients of institutions for the developmentally disabled.

· Prisoners.

· Immigrants from areas where the disease rate is high. (International travelers who spend long periods in such areas may also be at risk.)

People at highest risk for becoming chronic carriers of the virus include:

· Children infected before age 5, including newborns, most of whom become carriers.

· Infected people with damaged immune systems, such as AIDS patients.

Risk Factors for Hepatitis D. Hepatitis D occurs only in people with hepatitis B. It is not common in the U.S. and the incidence of this hepatitis is declining rapidly overseas. Experts anticipate that it will be extremely rare in the near future. Those who recover from hepatitis B are immune to further infection from both hepatitis B and D viruses.

Lifestyle Precautions for Preventing Hepatitis B and Hepatitis C Virus Transmission

The following are some precautions for preventing the transmission of hepatitits B or hepatitits C:

· All objects contaminated by blood from patients with hepatitis B or C must be handled with special care. (Restrictions on food preparation are not necessary for these hepatitis viruses.)

· Patients with viral hepatitis should abstain from sexual activity or take strict precautions. Infected patients should use condoms and contraceptives that prevent passage of the virus, possibly even in relationships that last for years. Women partners or infected women should abstain from sexual activity during menstruation. Either partner with infections that cause bleeding in the genital or urinary areas should avoid sexual activity until the infection is no longer active.

· Couples with an infected partner or people sharing household with an infected person should avoid sharing personal items, such as razors or toothbrushes.

Note: There is no evidence that the viruses can be passed through casual contact, or other contact without exposure to blood, including kissing, hugging, sneezing, or coughing or by sharing eating utensils or drinking glasses. People infected with chronic hepatitis B or C should not be excluded from work, school, play, childcare or any social or work settings on the basis of their infection.

Symptoms of Hepatitis B

Symptoms appear long after the initial infection, usually 4 - 24 weeks. Many patients may not even experience them or they may be mild and flu-like. About 10 - 20% of patients have a fever and rash. Nausea is not common. Sometimes there is general aching in the joints. The pain can resemble arthritis, affecting specific joints and accompanied by redness and swelling.

Outlook for Patients with Hepatitis B

Most people with hepatitis B recover from the virus. The risk of progressing to the chronic form of hepatitis B is age dependent. Only 2 - 6% of people who are older than 5 years old when they acquire the virus will develop chronic hepatitis B. The risk for chronic hepatitis in children age 1 - 5 years is 30%, and the risk for infants under the age of 1 is up to 90%. In the U.S., about 1.25 million people are chronically infected with hepatitis B. Worldwide, about 400 million people are chronically infected.

Chronic hepatitis B infection significantly increases the risk for liver damage, including cirrhosis and liver cancer. In fact, hepatitis B is the leading cause of liver cancer worldwide. According to a 2006 Lancet study, liver disease, especially liver cancer, is the main cause of death in people with chronic hepatitis B. Because of these high risks, it is very important that patients with chronic hepatitis B receive regular screenings for liver cancer.

Patients with hepatitis B who are co-infected with hepatitis D may develop a more severe form of acute infection than those who have only hepatitis B. Co-infection with hepatitis B and D increases the risk of developing acute liver failure. Patients with chronic hepatitis B who develop chronic hepatitis D also face high risk for cirrhosis. Hepatitis D occurs only in people who are already infected with hepatitis B.

Specific Tests for Identifying Hepatitis B

A diagnosis of hepatitis B relies on measuring the liver enzymes aspartate (AST) and alanine (ALT) -- released when the liver is damaged -- assays to identify the viral DNA, and a liver biopsy.

Doctors must then determine if the condition is chronic but inactive or whether it is more aggressive. This is done by identifying a specific antigen called HBsAg, which is a protein that is found in the blood in early stages of hepatitis B and suggests the presence of a viral replication. Most people develop antibodies to this antigen during convalescence. Their condition is referred to as HBeAG negative, or anti-HBe, and suggests that infection is on the wane. About 5 - 10% of people do not clear the infection but become carriers of the antigen (called HBsAG-positive). Evidence of its persistence for more than 6 months suggests that the condition is chronic.

Tests can identify specific genetic types of hepatitis B virus (designated A to G). It is not clear how significant they are in treating patients with hepatitits B.

It is important to remember, however, that viral levels are not an accurate measure of actual liver damage. Only a biopsy can determine this.

To diagnose hepatitis D using an antibody test, hepatitis B must already have been identified.

Preventing Hepatitis B and its Transmission

General precautions for preventing hepatitis B when traveling are the same as those for hepatitis A. In infected people, precautions for preventing transmission are similar to those for hepatitis C.

Vaccinations for Prevention of Hepatitis B. Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B and are safe even for infants and children. A triple-antigen hepatitis B vaccine (Hepacare) is proving to be effective for people who do not respond to the standard vaccines. Vaccination programs are also helping to reduce the risk for liver cancer. A combination vaccine (Twinrix) that contains Engerix-B and Havrix, a hepatitis A vaccine, is now approved for people with risk factors for both hepatitis A and B.

The hepatitis B vaccine is recommended for people who are at higher risk, including people who live with someone with hepatitis B and healthcare workers.

Until recently, the vaccine contained a mercury-based preservative called thimerosal. In response to concerns, professional organizations recommended suspending vaccinations in infants with noninfected mothers. In 1999, a thimerosal-free vaccine became available, and medical centers are now urged to continue vaccinations. Unfortunately, even after the thimerosal-free vaccine became available, a number of hospitals still have not restored vaccination of all infants. This is a safe vaccine. Parents should be sure their children are immunized.

Candidates for Hepatitits B Vaccinations. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade.

Typical schedules for hepatitis B vaccinations in childhood are as follows:

· All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be given by age 2 months if the mother has no evidence of infection. Infants of mothers infected with hepatitits B should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. Vaccinating the newborn prevents infection from being transmitted from mother to child.)

· The second dose should be given at least 4 - 6 weeks after the first dose. The third dose is given at least 8 weeks after the second dose (typically when the baby is 6 - 23 months old).

· Children who are 11 - 12 years old and who have not been immunized should receive two or three doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection lasts at least 10 years. Booster shots after that may be recommended, depending on continuing risk such as sexual exposure.

The following adults are at very high risk and should be vaccinated:

· Health care and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B virus that ranges from 15 - 30%.

· People in the same household as hepatitits B infected individuals. (Unvaccinated people who have had intimate exposure to people with hepatitits B may be protected with immune globulin, which is sometimes administered with the vaccine.)

· Travelers to developing countries.

· Patients who require transfusions and have not been infected with hepatitits B. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)

· Sexually active homosexual or heterosexual individuals with multiple partners or who engage in high-risk sexual behavior.

· People with any sexually transmitted diseases.

Other people at risk who may benefit from vaccinations include:

· Patients and workers in mental institutions and morticians.

· Patients on hemodialysis. (People on hemodialysis may need larger doses or boosters. They also may need to be re-vaccinated if blood tests indicate they are losing immunity.)

· People who use injected drugs.

· Pregnant women at risk for the virus should be vaccinated. There is no evidence that the vaccine is dangerous to the fetus.

· People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

The regimen in adults is typically three doses given over 6 months. People with alcoholism may need high doses.

Soreness at the injection site is the most common side effect. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and there has been some concern about three small studies associating the vaccine with an insignificant increase in multiple sclerosis. Recent studies, however, have found no evidence to support these concerns. Nonetheless, some groups oppose the vaccination in children who are not in high-risk groups. It should be strongly stressed that worldwide 65 million people with chronic hepatitis are expected to die from liver disease. Vaccinations save lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer.

Treatments for Chronic Hepatitis B

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

· Peginterferon alfa-2a (Pegasys)

· Interferon-alfa-2b (Intron)

· Adefovir (Hepsera)

· Lamivudine (Epivir)

· Entecavir (Baraclude)

· Telbivudine (Tyzeka)

These drugs block the replication of hepatitits B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the FDA approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitits B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitits B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitits B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitits B as the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitits B. Patients with lymphoma should be screened for hepatitits B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitits B and HIV should take entecavir only if they are also taking antiretroviral HIV drugs.

Investigational Drugs.

· Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitits B.

· Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitits B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.

· Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Liver Transplantation. If the disease progresses to liver failure, liver transplantation may be an option. It is not foolproof, however. Viral recurrence is high in patients with hepatitis B. However, regular, lifelong injections of hepatitis B immune globulin (HepaGam B) can reduce the risk for re-infection following liver transplantation.

In-Depth From A.D.A.M. Hepatitis C

Hepatitis C is spread by contact with infected human blood. It is the most common blood-borne infection in the country. Until blood screening began in 1990, the hepatitis C virus was primarily transmitted through blood transfusions. Now, hepatitis C is transmitted mainly through intravenous drug use and sharing needles. Nearly half of people infected with hepatitis C have a history of injecting drugs. People who received a blood transfusion before 1992 are also at high risk, as are people who have had 20 or more sexual partners. Hepatitis C can also be passed from an infected mother to her baby during birth. (Breast-feeding does not increase the risk of transmission.)

Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who engage in unprotected sex with multiple partners. About 4 million Americans have had an initial hepatitis C infection and an estimated 3.2 million have chronic hepatitis C. Hepatitis C affects about 170 million people worldwide. Most people with chronic hepatitis C are unaware that they have it. It is not possible to predict which patients will develop the chronic form of hepatitis C.

Ethnic Groups. In general, hepatitis C occurs most commonly in non-Caucasian men ages 30 - 49 years. Over 6% of African-Americans are infected with hepatitis C, about two to three times the risk for Caucasians.

Symptoms of Hepatitis C

Most patients with hepatitis C do not experience symptoms. If they appear at all, symptoms develop about 1 – 2 months after a person is infected. Symptoms of progressive chronic viral hepatitis may be very subtle. In some patients, itchy skin is the first symptom. Overall, fatigue is the most common symptom. Many patients do not experience any symptoms at all. Chronic hepatitis C can be present for 10 - 30 years, and cirrhosis or liver failure can sometimes develop before patients experience any clear symptom.

Some evidence suggests, however, that patients with chronic hepatitis C often experience an impaired quality of life, mostly from fatigue. Fatigue can impair daily function, vitality, and mood in ways that are similar to other chronic diseases. The severity of the fatigue is not necessarily related to the degree of liver injury. Some patients develop pain in small joints in the body (such as the hand) that may be nearly indistinguishable from symptoms of rheumatoid arthritis, fibromyalgia, or carpal tunnel syndrome. Recent research suggests that sexual dysfunction may be common among men with chronic hepatitis C. Other nonspecific symptoms include abdominal discomfort, loss of appetite, depression, and difficulty concentrating.

Outlook for Patients with Hepatitis C

Acute Form. Acute hepatitis C is rarely recognized, since there are no symptoms in up to 80% of patients. About 15 - 45% of acute cases clear up on their own without becoming chronic. Early treatment with interferon drugs can significantly reduce the risk for progression to chronic hepatitis.

Chronic Form. About 55 - 85% of infected people develop chronic hepatitis. Chronic hepatitis C poses a risk for cirrhosis, liver cancer, or both.

· Five - 20% of patients with chronic hepatitis C develop cirrhosis over a period of 20 – 30 years. The longer the patient has had the infection, the greater the risk. Patients who have had hepatitis C for more than 60 years have a 70% chance of developing cirrhosis.

· Seventy percent of patients with chronic hepatitis C eventually develop chronic liver disease.

· Of these patients, 4% eventually develop liver cancer. (Liver cancer rarely develops without cirrhosis first being present.)

About 1 - 5% of people with chronic hepatitis C eventually die from liver diseases (cirrhosis or liver cancer). However, according to a 2006 Lancet study, intravenous drug-related deaths are more common than liver-related deaths among younger female patients (ages 15 - 24) infected with hepatitis C or hepatitis C and B.

Patients with chronic hepatitis C may also be at higher risk for non-liver disorders, including the following:

· Cryoglobulinemia (a disorder in which protein clumps form in the blood). This can cause skin rash and ulcers, kidney problems, arthritis, and sensations (such as tingling or pain) in the hands and feet. People with such symptoms may have particular difficulties with interferon, which can have similar side effects.

· Porphyria cutanea tarda (a disorder that causes skin color and texture changes and sensitivity to light).

· Certain autoimmune disorders, particularly hypothyroidism and rheumatoid arthritis.

· Type 2 diabetes, particularly among younger people with hepatitis C who are overweight.

· Some experts believe that hepatitis C may infect the central nervous system in certain patients, possibly accounting for the fatigue, depression, or both experienced by patients who have even relatively mild cases.

· Certain types of lymphomas (cancers of the lymphatic system). According to a 2007 study in the Journal of the American Medical Association, hepatitis C infection increases the risk of developing non-Hodgkin’s lymphoma by 20 - 30%. The risk for a particular type of non-Hodgkin’s lymphoma, Waldenstrom’s macroglobulinemia, increases by 300%. However, this study only evaluated male Vietnam War veterans, so these risks may not apply to the general public.

Specific Tests for Identifying Hepatitis C and Determining its Severity

Tests for Liver Enzymes. Blood tests showing elevated liver enzymes, particularly alanine aminotransferase (ALT), plus symptoms of hepatitis (jaundice, fatigue) are often first signs of acute hepatitis. In chronic hepatitis, however, liver enzymes may be normal or fluctuate. They also can be elevated even after the virus has cleared.

Tests to Identify the Virus. The standard first test for diagnosing hepatitis C is known as enzyme-linked immunosorbent assay (ELISA or EIA). The antibody for hepatitis C is used to identify the virus. The antibody may not show up for 6 weeks to 1 year after the onset of the disease, however, so its absence is not necessarily an indication of a healthy liver. A test called an immunoblot assay (called RIBA) may also be used to confirm the presence of the virus. An accurate home test (Hepatitis C Check) is now available. It supplies a lancet for obtaining a drop of blood, which is sent to the laboratory for EIA and possibly RIBA analysis. Results take about a week.

Tests to Identify Genetic Types and Viral Load. Additional tests called hepatitis C RNA assays may be used to confirm the diagnosis. They use a polymerase chain reaction (PCR) to detect the RNA (the genetic material) of the virus. Such tests may be performed if there is some doubt about a diagnosis but the doctor still firmly believes the virus is present.

hepatitis C RNA assays also determine virus levels (called viral load). Such levels do not reflect the severity of the condition or speed of progression, as they do for other viruses, such as HIV. However, high viral loads suggest a poorer response to treatment with interferons.

Such techniques may also help determine the genotype of the virus, which can be helpful in determining a treatment approach. There are six main genetic types of hepatitis C and more than 50 subtypes. They do not appear to affect the rate of progression of the disease itself, but they can differ significantly in their effects on response to treatment. Genotype 1 is the most difficult to treat and is the cause of up to 75% of the cases in the U.S. The other common genetic types are types 2 (15%) and 3 (7%), which are more responsive to treatment. People with hepatitis C need to have their genotype tested so that doctors can make appropriate treatment recommendations.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Liver Biopsy. Only a biopsy can determine the extent of injury in the liver. Some doctors now recommend biopsies for all patients with chronic hepatitis C, regardless of severity, because of the risk for liver damage even in patients without symptoms. If a biopsy does not show any scarring and liver enzymes are normal, patients can be assured that the outlook is very favorable.

Prevention of Hepatitis C

No vaccines are available, but immune globulin helps protect against developing hepatitis C after transfusions. Periodic doses of immune globulin in sexual partners of infected people also appear to be protective. In infected people, preventing transmission is similar to those for hepatitis B.

Treatments for Chronic Hepatitis C

Interferons. Interferons are natural proteins that activate certain immune functions in the body and have anti-viral properties. The natural interferons used for chronic hepatitis B and C are called type I interferons. They are given by injection, need to be taken three times a week, and include the following:

· Interferon alfa 2b (Intron A). Used for both hepatitis B and C.

· Interferon alfa 2a (Roferon-A). Mostly used for hepatitis C.

· Interferon alfa-n1 (Wellferon). Approved but mostly used in Canada for hepatitis C.

Newer synthetic interferons have been developed that are showing some advantages over the natural forms:

· Pegylated interferon (PegINF). Pegylated interferons use a small molecule called polythelene glycol (PEG), which attaches to a protein and extends the activity of the interferon. This action allows the drug to be taken only once a week. Drugs available include pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys).

· Interferon alfacon-1 (Infergen). This drug is called a consensus interferon (CIFN) because it was genetically developed using the most commonly occurring amino acid sequences from each of the natural type 1 alpha interferons. It is 5 - 10 times more biologically active than natural type 1 interferons. CIFN is usually given three times a week when used as initial treatment for hepatitis C.

Interferon Candidates. The best candidates for interferon treatments are patients who are at greatest risk for cirrhosis. Factors suggesting a higher risk for cirrhosis include:

· Detectable virus levels as determined by an assay test.

· High levels of aminotransferase enzyme for more than 6 months.

· Indication of liver scarring on biopsy.

Patients who are not good candidates for interferon and are usually ineligible include:

· Women who are pregnant or planning to become pregnant soon.

· Patients with advanced cirrhosis. (It is unclear if the drug improves survival in patients with advanced cirrhosis and, in any case, it may be dangerous for them.)

· Patients with fluid in the abdomen (ascites).

· Patients with anemia or risk factors for anemia should not take the combination treatments, although they may be candidates for interferon alone.

Several kinds of patients are ineligible for treatment because of the high risk for noncompliance and the severe psychiatric effects of the drugs. They include patients with psychiatric and medical problems and substance abusers. Some doctors believe that these patients could benefit from treatment.

Side Effects and Complications of Treatment with Interferon. Common side effects of any interferon are flu-like symptoms (fever, chills, muscle aches) that usually occur within 6 hours and gradually decline over 1 - 2 weeks. (Pegylated interferon may pose a higher risk for these symptoms than the natural interferons.)

Chronic or more serious effects include:

· Emotional and mental changes. Depression can be very severe, and cases of suicidal thoughts have been reported. Other mental and emotional symptoms include anxiety, amnesia, confusion, irritability, impaired concentration, decreased alertness, memory problems, and mental slowing.

· Changes in sensation.

· Weight loss.

· Skin rashes.

· Hair loss.

· Gastrointestinal problems, including nausea, vomiting, and diarrhea, and, in severe cases intestinal bleeding and ulcers.

· Fatigue and general weakness.

· Back pain.

· Complications in the lungs, including worsening of asthma. In severe cases, interferon can cause shortness of breath, inflammation in the lungs, and pneumonia.

· Possible negative effects on cholesterol and lipid levels.

· Heart rhythm disturbances, which, in rare cases, can be serious.

· Mild anemia.

· Drop in platelet and white blood cell counts, increasing susceptibility to bacterial infections.

· May trigger an autoimmune response, possibly causing anemia, diabetes, lupus-like symptoms, hypothyroidism, or even autoimmune hepatitis.

· Complications in the eye, including bleeding that, in some cases, may lead to loss of vision if not detected promptly.

· Rare reports of acute pancreatitis.

· In children, interferon therapy temporarily disrupts growth.

Patients have a difficult time with prolonged therapy. Over 20% drop out if treatment lasts longer than 2 years. Depression is the most common reason for stopping the treatment.

Several different methods of administering interferons are under investigation to help reduce some of the problems associated with injections. These methods include pills, pumps, and controlled release implants.

Interferons in Combination with Ribavirin. Ribavirin, a nucleoside analog drug, does not work alone, but it can double sustained response rates when combined with an interferon.

Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with hepatitis C genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavirin.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavirin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations may help slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

· Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.

· Flu-like symptoms such as fever, headaches, and muscle aches are the most common side effect.

· Reduced white blood cell count.

· Skin disorders such as dry skin and rash.

· Coughing and shortness of breath.

· Gastrointestinal symptoms (nausea, indigestion, lack of appetite).

· Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.

· Combination treatment in pregnant women poses a very high risk for birth defects.

Determining Treatment Success. Doctors measure treatment success and approaches based on the patient’s response to the treatments:

· Early Response. These are patients who respond to the drug right away. This means that their viral count drops very rapidly within the first few weeks of treatment and is still undetectable at 12 weeks. (One difficulty in deciding when to stop treatment, even in responders, is the inability to predict at 12 weeks which of these patients will relapse and which ones will have a sustained response.)

· Sustained Response. Patients who are free of the virus longer than 6 months are considered to be sustained responders. The overall sustained response rates with the current standard combination of pegylated interferon and ribavirin is over 50%, with certain factors predicting higher or lower response rates.

· Relapse. In relapse, the virus comes back again and requires retreatment. This is usually due to the development of mutant strains that are resistant to the drugs or because the original dose was too low.

· Nonresponse. Patients are considered to be nonresponders if the virus is still detectable 12 weeks after interferon alone or after 24 weeks of combination therapy. Treating these patients again has achieved only a 15% response.

People at Risk for Poor Response to Combination Treatment. The following patients have a greater risk for not responding to combination treatment with interferon and ribavirin:

· People at high risk for aggressive hepatitis C.

· Having a high viral count.

· Having a specific genetic type of the virus. Patients with genotype 1 do not respond as well to combination treatment as patients with genotypes 2 or 3.

· Older age (especially older than 60 years).

· African-Americans are less responsive to treatment than Caucasians or Asians. The reasons for this are unclear.

Failure can be due to other, modifiable factors, which should be assessed before stopping treatment, particularly in patients who had interferon alone. They include:

· Interferon dose was too low.

· Patient did not comply fully with the treatment.

· Patient was consuming alcohol.

· Treatment time was too short. Some evidence suggests that response can significantly improve for many patients with genotype 1 if treatment time is extended to 48 weeks.

Even if viral levels linger, interferon treatment may still have benefits. For example, patients with normal liver enzyme levels appear to have almost no risk for liver damage, even if viral levels persist after treatment. Evidence also suggests that interferon reduces liver scarring and may reduce the risk for liver cancer in some patients, even if the treatment does not eliminate the virus. More research is needed, however, to confirm these findings.

Investigational Drugs for Hepatitis C. The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs that may show promise include:

· Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavirin in Phase II trials for patients with genotype 1 chronic hepatitis C.

· Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T cells). It is being used for hepatitis B and is under investigation for hepatitis C in combinations interferon.

· Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.

· Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.

· Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Other drugs under investigation include vaccines, genetic therapies known as antisense oligonucleotides or monoclonal antibodies, and drugs that will help prevent or reduce progression of liver scarring or progression to liver cancer. Even if successful, none of these drugs will be available for many years.

Liver Transplantation for Hepatitis C. If the disease progresses to the point where it becomes life-threatening, liver transplantation may be an option. Nearly 40% of liver transplant patients are infected with hepatitis C. However, liver transplantation is not a cure for hepatitis C. The virus nearly always returns. One study of patients with hepatitis C reported 5-year risks for viral recurrence of 80% and for cirrhosis of 10%. A 2004 study found that the hepatitis C virus comes back with more severity in livers from living donors than livers taken from cadavers. Researchers are investigating retreatment with antiviral drugs.

Disease Recurrence

In both hepatitis B and C, the disease often persists or returns despite treatment. The virus continually generates many “mutant viruses” that differ just slightly from the parent virus. These mutated viruses may be resistant to interferons and so, over time, the drugs become ineffective.

In-Depth From A.D.A.M. Autoimmune Hepatitis

Autoimmune chronic hepatitis typically occurs in women ages 20 - 40 who have other autoimmune diseases, including:

· Systemic lupus erythematosus

· Rheumatoid arthritis

· Sjögren's syndrome

· Inflammatory bowel disease

· Glomerulonephritis

· Hemolytic anemia

Some research indicates that the postmenopausal period may be another peak in incidence of autoimmune hepatitis among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, researches have not discovered major risk factors for this condition.

Symptoms of Autoimmune Hepatitis (AIH)

About 85% of people with chronic active autoimmune hepatitis do not have severe symptoms. When symptoms occur, they range from minimal to severe, and include fatigue, jaundice, fever, and weight loss. The liver and spleen are often enlarged. In addition, patients with this condition may experience skin disorders, including palmar erythema (red palms) and spider angioma (a blood-red spot, the size of a pinhead, from which tiny blood vessels radiate like spider legs). Itching is not common, however. The abdomen or legs may be swollen due to the accumulation of fluid.

Tests for Autoimmune Chronic Hepatitis

If a patient has symptoms of chronic active hepatitis for 6 months or more and a virus cannot be identified, doctors usually suspect autoimmune hepatitis. Other autoimmune liver diseases, however, can confuse a diagnosis. To help confirm this condition, test results may show high levels of immune factors called serum globulins or certain antibodies to liver proteins. In some cases, a successful trial of steroid drugs may be the only way to diagnose autoimmune hepatitis.

Outlook for Autoimmune Hepatitis

Autoimmune hepatitis is usually benign and causes little trouble. There is a very small risk that it can evolve into the active form. One study reported a 10-year survival rate of 95%, which was similar to the same age group in the general population. However, it the condition evolves into the chronic active form, 5-year survival may be only 50% if the disease is not treated. (The survival rate can be higher in people with milder symptoms and less liver damage.)

Although very uncommon, severe autoimmune hepatitis can be life-threatening and require intensive therapy, possibly including liver transplantation. The risk for liver failure and bleeding in the stomach and esophagus is highest in the early years after disease onset. This risk diminishes over time but is replaced by an increase in liver cancer rates and bleeding in the stomach and intestines. The risk for liver cancer is not as high, however, as with chronic viral hepatitis.

Treatments for Autoimmune Hepatitis

Patients with autoimmune hepatitis who have mild symptoms and slight inflammation of the liver do not require any treatment except to relieve symptoms. They should be monitored, however, for any signs of disease progression. Severe autoimmune hepatitis is a life-threatening condition and requires intensive therapy.

Because of effective treatment options and in spite of a high rate of relapse, long-term survival rates in patients with autoimmune hepatitis are excellent. Drugs that block factors in the immune system and help reduce inflammation and symptoms of autoimmune hepatitis are most often used.

Corticosteroids. The corticosteroid prednisone (Deltasone, Orasone, Sterapred, generic) is the standard drug for treating autoimmune hepatitis. It produces remission of symptoms in about 80% of patients with autoimmune hepatitis. For most patients, steroids also reduce symptoms within 3 months, improve liver function within 6 months, and restore liver health within 2 years. Between 10 - 20% of patients continue to deteriorate despite steroid treatment, although higher doses may help some of these people. (Steroids are generally not useful for chronic hepatitis B or C. Suppressing the immune system in these patients can actually encourage the viruses to multipy more quickly.)

Treatment usually needs to continue for about 2 years before the disease is in complete remission. Usually, steroids are stopped when disease symptoms have disappeared, when blood tests show that aminotransferase (AST) levels are less than two times normal, and liver biopsies reveal no active cell damage. Steroid medications must be withdrawn very slowly. Patients who are very elderly or who have advanced (decompensated) cirrhosis are not good candidates for this treatment.

Unfortunately, remission rarely lasts more than 3 years. About half of patients relapse within 6 months, and only about 20% of patientsare disease-free for more than 5 years. A 2007 study indicated that AST, gamma-globulin, and immunoglobulin-G (IgG) levels are helpful in predicting which patients may relapse and which patients have the best chance for maintaining remission. Still, most patients with autoimmune hepatitis will eventually have a relapse. Re-administering prednisone therapy after relapse achieves another remission in about 80% of patients.

Corticosteroid side effects can be very distressing and sometimes serious. They include weight gain, skin problems, moon-shaped face, high blood pressure, diabetes, cataracts, mental disturbances, infections, and osteoporosis.

Azathioprine. Doctors often prescribe the drug azathioprine (Imuran) along with steroids to help reduce severe side effects caused by using steroids alone. When azathioprine is given in combination with prednisone, the prednisone dose can be reduced, thereby lowering the corticosteroid’s side effects. Azathioprine also suppresses the immune system and helps prevent relapse, but the drug will not induce remission by itself.

Other Drugs. Other immunosuppressant drugs, such as mycophenylate mofetil (MMF), cyclosporine (Neoral), or tacrolimus (Prograf) are sometimes prescribed for patients who are not helped by standard treatment.

Liver Transplantation and Autoimmune Hepatitis. If all therapies fail and the disease becomes life threatening, liver transplantation may be performed. Liver transplantation can be a successful option for many people. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years.

In-Depth From A.D.A.M. Symptom Management

The primary goals for managing viral hepatitis are to provide adequate nutrition, to prevent additional damage to the liver, and to prevent transmission to others. For mild cases of acute viral hepatitis, no drug therapy or other treatment is either available or necessary. Hospitalization is needed only for people at high risk for complications such as pregnant women, elderly people, patients with other serious conditions, or those who have severe nausea and vomiting and need to have fluids administered intravenously.

The following tips may be useful:

· All patients should abstain from alcohol and sexual contact during the acute phase.

· Although most patients with hepatitis experience fatigue and require more rest than usual, they can be as physically active as they want without affecting recovery. In fact, patients should be encouraged to be as active as they can.

· Depression is common, particularly in people used to an active life. Patients should be reassured that in the majority of hepatitis cases, recovery is complete.

· The liver processes many types of medications. As soon as hepatitis is diagnosed, patients should stop taking all drugs (including over-the-counter-medication) except those prescribed or recommended by their doctors. Specific nonsteroidal anti-inflammatory drugs (NSAIDs) that should be avoided include ibuprofen (Advil, Motrin) and acetaminophen (Tylenol). Ibuprofen (Advil, Motrin) may increase liver enzymes and cause liver damage in patients with hepatitis C. Acetaminophen (Tylenol) may cause sudden liver failure in patients with hepatitis A or B. Acetaminophen can also damage the liver if taken in combination with alcohol.

After the onset of acute hepatitis, periodic visits to the doctor for repeat blood tests are necessary, the frequency of which depends on how well the patient feels. If symptoms still occur after 3 months and laboratory tests still indicate active presence of the virus, the patient should be evaluated every month. If symptoms persist beyond 6 months, a liver biopsy may be required to determine any liver damage.

Dietary Factors to Protect the Liver. In general, no vitamins or special diets have been proven to be particularly beneficial. The following may be helpful, however:

· Eating many small snacks during the day, with larger ones in the morning, may help prevent weight loss while reducing the severity of nausea. Patients might be able to tolerate high-caloric drinks to supplement their regular diet.

· One small Japanese study suggested that vitamin E might help protect against liver damage in patients with hepatitis C.

· Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. Pork is high in the vitamin, but more healthy sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

· Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

· Higher coffee intake has been shown to reduce the risk for cirrhosis.

Herbs and Supplements

Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Popular herbal remedies for hepatitis include ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), and silymarin (found in milk thistle). Aside from milk thistle, there has been no evidence that these herbs are helpful for hepatitis. Studies on milk thistle’s benefit have been mixed. Some studies have indicated that milk thistle may help improve liver enzyme levels. However, a 2005 review found that the herb did not reduce deaths from liver disease caused by hepatitis B or C.

Patients with hepatitis should be aware that some herbal remedies may cause liver damage. In particular, kava (an herb used to relieve anxiety and tension) may be dangerous for people with chronic liver disease.

In-Depth From A.D.A.M. Outlook

In most cases of acute viral hepatitis, recovery is complete and the liver returns to normal within 2 - 8 weeks. In a small number of cases of hepatitis B or C, the condition can be prolonged and recovery may not occur for a year. About 5 - 10% of these patients will have a flare-up of milder symptoms before full recovery. A few of these patients may go on to develop chronic hepatitis. People who have been infected with a hepatitis virus continue to produce antibodies to that specific virus. This means that they cannot be reinfected with the same hepatitis virus again. Unfortunately, they are not protected from other types.

Serious consequences of acute viral hepatitis are rare, but can be life threatening if they occur. Pregnant women with acute hepatitis B, C, or E are at higher risk for complications of acute hepatitis.

In very rare cases, within 2 months of onset of acute hepatitis, a very serious condition known as fulminant hepatitis can develop. In this event, the liver fails with catastrophic consequences. The following events may develop:

· A large swollen abdomen (known as ascites) and a peculiar hand-flapping tremor (called asterixis).

· These symptoms may be followed by stomach and intestinal bleeding and mental confusion, stupor, or coma caused by brain injury (encephalopathy).

No medications, including corticosteroids, have any effect against the condition itself. Liver transplantation is currently the only life-saving treatment for fulminant acute hepatitis and has survival rates of up to 60%. Without liver transplantation, the chance of survival is only 20%.

Other serious and rare consequences of acute viral hepatitis are aplastic anemia (which can be fatal), pancreatitis, hypoglycemia, and polyarteritis, a serious inflammation of blood vessels.

General Prognosis for Chronic Hepatitis

Chronic Persistent Hepatitis. Chronic persistent hepatitis is usually mild and nonprogressive or slowly progressive, causing limited damage to the liver. Cell injury in such cases is usually limited to the region of portal tracts, which contains vessels that carry blood to the liver from the digestive tract. In some cases, however, more extensive liver damage can occur over long periods of time and progress to chronic active hepatitis.

Chronic Active Hepatitis. If damage to the liver is extensive and cell injury occurs beyond the portal tract, chronic active hepatitis can develop. Significant liver damage has usually occurred by this time. Nearly every bodily process is affected by a damaged liver, including digestive, hormonal, and circulatory systems. Symptoms can significantly impair daily life.

· Cirrhosis. If liver cells are destroyed between the portal tract and the central veins in the liver, progressive cell damage can build a layer of scar tissue over the liver, resulting in the condition known as cirrhosis. In such cases, the entire liver is threatened with malfunction and failure. If cirrhosis develops, the average survival time is about 10 years. The risk for cirrhosis is much higher in patients with hepatitis C than in those with hepatitis B. <!--[For more information, see In-Depth Report #75: Cirrhosis.]-->

· Liver Cancer. The risk for liver cancer in patients with cirrhosis is about 14% but varies widely depending on the cause of hepatitis. (Liver cancer is rare in patients who do not develop cirrhosis.)

A chronic liver disease which causes damage to liver tissue, scarring of the liver (fibrosis; nodular regeneration), progressive decrease in liver function, excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis

Liver Transplantation

Liver transplantation may be indicated for the following patients:

· Those who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.

· Patients with liver cancer that has not spread beyond the liver.

Current 5-year survival rates after liver transplantation are 55 - 80%, depending on different factors. Patients report improved quality of life and mental functioning after liver transplantation. Unfortunately, in about half of all patients with chronic hepatitis, the disease recurs after transplantation.

Patients should consider medical centers that have performed more than 50 transplants per year and produced better-than-average results. Unfortunately, there are far more people waiting for liver donors than there are available organs. <!--[For more information on liver transplantation, see In-Depth Report #75: Cirrhosis.]-->

In-Depth From A.D.A.M. References

Amin J, Law MG, Bartlett M, Kaldor JM, Dore GJ. Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study. Lancet. 2006 Sep 9;368(9539):938-45.

Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H, et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA. 2007 May 9;297(18):2010-7.

Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-51. Epub 2006 Sep 20.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Montano-Loza AJ, Carpenter HA, Czaja AJ. Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse. Am J Gastroenterol. 2007 May;102(5):1005-12. Epub 2007 Feb 23.

Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34.

Wang CS, Wang ST, Yao WJ, Chang TT, Chou P. Hepatitis C virus infection and the development of type 2 diabetes in a community-based longitudinal study. Am J Epidemiol. 2007 Jul 15;166(2):196-203. Epub 2007 May 11.

What is a tumor?

Tumors are abnormal masses of tissue that form when cells begin to reproduce at an increased rate. The liver can grow both non-cancerous (benign) and cancerous (malignant) tumors.

What are non-cancerous liver tumors?

Non-cancerous (benign) tumors are quite common and usually do not produce symptoms. Often, they are not diagnosed until an ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) scan is performed. There are several types of benign liver tumors, including the following:

hepatocellular adenoma

This benign tumor occurs most often in women of childbearing age. Most of these tumors remain undetected. Sometimes, an adenoma will rupture and bleed into the abdominal cavity, requiring surgery. Adenomas rarely become cancerous.

hemangioma

This type of benign tumor is a mass of abnormal blood vessels. Up to five percent of adults have small liver hemangiomas that cause no symptoms. Treatment is usually not required. Sometimes, infants with large liver hemangiomas require surgery to prevent clotting and heart failure.

What are cancerous liver tumors?

Cancerous (malignant) tumors in the liver have either originated in the liver (primary liver cancer) or spread from cancer sites elsewhere in the body (metastatic liver cancer). Most cancerous tumors in the liver are metastatic.

What is hepatoma (primary liver cancer)?

Also called hepatocellular carcinoma, this is the most common form of primary liver cancer. Chronic infection with hepatitis B and C increases the risk of developing this type of cancer. Other causes include cancer-causing substances, alcoholism, and chronic liver cirrhosis.

What are the symptoms of a liver hepatoma?

The following are the most common symptoms of a liver hepatoma. However, each individual may experience symptoms differently. Symptoms may include:

abdominal pain

weight loss

nausea

vomiting

large mass can be felt in upper, right part of abdomen

fever

jaundice - yellowing of the skin and eyes.

The symptoms of a liver hepatoma may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

How is liver hepatoma diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for a liver hepatoma may include the following:

liver function tests - a series of special blood tests that can determine if the liver is functioning properly.

abdominal ultrasound (Also called sonography.) - a diagnostic imaging technique which uses high-frequency sound waves to create an image of the internal organs. Ultrasounds are used to view internal organs of the abdomen such as the liver spleen, and kidneys and to assess blood flow through various vessels.

computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure using a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

hepatic arteriography - x-rays taken after a substance in injected into the hepatic artery.

liver biopsy - a procedure in which tissue samples from the liver are removed (with a needle or during surgery) from the body for examination under a microscope.

Treatment for liver hepatoma:

Specific treatment for liver hepatoma will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

your tolerance of specific medicines, procedures, or therapies

expectations for the course of the disease

your opinion or preference

Treatment may include:

surgery Surgery may be necessary to remove cancerous tissue, as well as nearby non-cancerous tissue. Total surgical removal of the liver lobe or removal of segments of the liver may be performed.

radiation therapy Radiation therapy uses high-energy rays to kill or shrink cancer cells.

chemotherapy Chemotherapy uses anticancer drugs to kill cancer cells.

liver transplantation

What are other types of primary liver cancers?

Other, less common primary liver cancers include the following:

cholangiocarcinoma - a cancer that originates in the lining of the bile channels in the liver or in the bile ducts.

hepatoblastoma - a common cancer in infants and children, sometimes causing the release of hormones that result in early puberty.

angiosarcoma - a rare cancer that originates in the blood vessels of the liver.

What are the stages of liver cancer?

When a physician diagnoses liver cancer, the next step is to determine how far the cancer cells have spread (a process called staging). The National Cancer Institute defines the following stages for primary liver cancer:

localized resectable	Cancer is in one place and can be removed completely with surgery.
localized unresectable	Cancer is in one place, but cannot be totally removed.
advanced	Cancer has spread through the liver and other parts of the body.
recurrent	Cancer has come back after it was treated.

What is metastatic liver cancer?

Cancer that has spread from other areas in the body to the liver usually originated in the lung, breast, colon, pancreas, and stomach. Leukemia and other blood cancers sometimes also spread to the liver.

What are the symptoms of metastatic liver cancer?

The following are the most common symptoms of metastatic liver cancer. However, each individual may experience symptoms differently. Symptoms may include:

weight loss

poor appetite

enlarged, hard and tender liver

fever

enlarged spleen

ascites - fluid build-up in the abdominal cavity.

jaundice - yellowing of the skin and eyes.

confusion

drowsiness

The symptoms of metastatic liver cancer may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

How is metastatic liver cancer diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for metastatic liver cancer may include the following:

liver function tests - a series of special blood tests that can determine if the liver is functioning properly.

abdominal ultrasound (Also called sonography.) - a diagnostic imaging technique which uses high-frequency sound waves to create an image of the internal organs. Ultrasounds are used to view internal organs of the abdomen such as the liver spleen, and kidneys and to assess blood flow through various vessels.

computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure using a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

liver biopsy - a procedure in which tissue samples from the liver are removed (with a needle or during surgery) from the body for examination under a microscope.

Treatment for metastatic liver cancer:

Specific treatment for metastatic liver cancer will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

your tolerance of specific medicines, procedures, or therapies

expectations for the course of the disease

your opinion or preference

Treatment may include:

surgery Surgery may be necessary to remove cancerous tissue, as well as nearby non-cancerous tissue. The most common operation is called gastrectomy, or surgical removal of all or part of the stomach. If part of the stomach is removed, it is called a subtotal or partial gastrectomy. If the entire stomach is removed, it is called a total gastrectomy.

radiation therapy Radiation therapy uses high-energy rays to kill or shrink cancer cells.

chemotherapy Chemotherapy uses anticancer drugs to kill cancer cells.

Other Liver Disorders

What are autoimmune liver disorders?

An autoimmune disorder is any reaction or attack of a person's immune system against its own organs and tissues. In the liver, the immune system can destroy liver cells and damage bile ducts. Chronic active hepatitis can be caused by an autoimmune disorder.

What are metabolic liver disorders?

Two main metabolic disorders affect the liver:

hemochromatosis (Also called iron overload disease.) - characterized by the absorption of too much iron from food. Instead of secreting the excess iron, the iron is stored throughout the body, including the liver and pancreas. The excess iron can damage these organs. Hemochromatosis is a hereditary disease that can lead to liver disease, liver failure, liver cancer, heart disease, and diabetes.

Wilson's disease - characterized by the retention of too much copper in the liver. Instead of releasing the copper into the bile, the liver retains the copper. Eventually, the damaged liver releases copper into the bloodstream. This hereditary disease can cause damage to the kidneys, brain, and eyes, and can lead to severe brain damage, liver failure, and death.

The Pancreas: Anatomy and Functions

Anatomy of the pancreas:

The pancreas is an elongated, tapered organ located across the back of the abdomen, behind the stomach. The right side of the organ (called the head) is the widest part of the organ and lies in the curve of the duodenum (the first section of the small intestine). The tapered left side extends slightly upward (called the body of the pancreas) and ends near the spleen (called the tail).

The pancreas is made up of two types of tissue:

exocrine tissue The exocrine tissue secretes digestive enzymes. These enzymes are secreted into a network of ducts that join the main pancreatic duct, which runs the length of the pancreas.

endocrine tissue The endocrine tissue, which consists of the islets of Langerhans, secretes hormones into the bloodstream.

Functions of the pancreas:

The pancreas has digestive and hormonal functions:

The enzymes secreted by the exocrine tissue in the pancreas help break down carbohydrates, fats, proteins, and acids in the duodenum. These enzymes travel down the pancreatic duct into the bile duct in an inactive form. When they enter the duodenum, they are activated. The exocrine tissue also secretes a bicarbonate to neutralize stomach acid in the duodenum.

The hormones secreted by the endocrine tissue in the pancreas are insulin and glucagon (which regulate the level of glucose in the blood), and somatostatin (which prevents the release of the other two hormones).

Disorders of the Pancreas

There are many disorders of the pancreas that require clinical care by a physician or other healthcare professional. Listed in the directory below are some, for which we have provided a brief overview.

If you cannot find the information in which you are interested, please visit the Liver Disorders Online Resources page in this Web site for an Internet/World Wide Web address that may contain additional information on that topic.

Pancreatitis

When Acute Pancreatitis Strikes

Women are one-and-a-half times more likely than men to have acute pancreatitis caused by gallstones. On the other hand, men are six times more likely than women to have acute pancreatitis caused by alcoholism.

What is pancreatitis?

Pancreatitis is the inflammation and autodigestion of the pancreas. Autodigestion describes a process whereby pancreatic enzymes destroy its own tissue leading to inflammation. The inflammation may be sudden (acute) or ongoing (chronic). Acute pancreatitis usually involves a single "attack," after which the pancreas returns to normal. Severe acute pancreatitis can be life threatening. In chronic pancreatitis, permanent damage occurs to the pancreas and its function, often leading to fibrosis (scarring).

What causes pancreatitis?

The most common causes of pancreatitis include the following:

gallstones that block the pancreatic duct

alcohol abuse, which can lead to blockage of the small pancreatic ductules

Other causes of pancreatitis include the following:

abdominal trauma or surgery

kidney failure

lupus

infections such as mumps, hepatitis A or B, or salmonella

cystic fibrosis

presence of a tumor

a venomous sting from a scorpion

What are the symptoms of pancreatitis?

The following are the most common symptoms of pancreatitis. However, each individual may experience symptoms differently. Symptoms may include:

abdominal pain that may radiate to the back or chest

nausea

vomiting

rapid pulse rate

feeling ill

fever

swelling in the upper abdomen

ascites - fluid build-up in the abdominal cavity.

dropping blood pressure

mild jaundice - yellowing of the skin and eyes.

Severe abdominal pain in the upper abdomen is usually a symptom of acute pancreatitis. The symptoms of pancreatitis may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

How is pancreatitis diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for pancreatitis may include the following:

abdominal x-ray - a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.

various blood tests

ultrasound (Also called sonography.) - a diagnostic imaging technique which uses high-frequency sound waves to create an image of the internal organs. Ultrasounds are used to view internal organs of the abdomen such as the liver spleen, and kidneys and to assess blood flow through various vessels.

endoscopic retrograde cholangiopancreatography (ERCP) - a procedure that allows the physician to diagnose and treat problems in the liver, gallbladder, bile ducts, and pancreas. The procedure combines x-ray and the use of an endoscope - a long, flexible, lighted tube. The scope is guided through the patient's mouth and throat, then through the esophagus, stomach, and duodenum. The physician can examine the inside of these organs and detect any abnormalities. A tube is then passed through the scope, and a dye is injected which will allow the internal organs to appear on an x-ray.

computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure using a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

electrocardiogram (ECG or EKG) - a test that records the electrical activity of the heart, shows abnormal rhythms (arrhythmias or dysrhythmias), and detects heart muscle damage.

Treatment for pancreatitis:

Specific treatment for pancreatitis will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

your tolerance of specific medicines, procedures, or therapies

expectations for the course of the disease

your opinion or preference

The overall goal for treatment of pancreatitis is to rest the pancreas and allow it to recover from the inflammation.

Treatment may include:

hospitalization for observation and intravenous (IV) feeding

surgery

antibiotics

avoiding alcohol (if the pancreatitis is caused by alcohol abuse)

pain management

frequent blood tests (to monitor electrolytes and kidney function)

no food by mouth for several days

bed rest or light activity only

placement of a nasogastric tube (tube inserted into the nose that ends in the stomach)

Individuals with chronic pancreatitis may also require:

enzyme supplements to aid in food digestion.

insulin (if diabetes develops).

small high-protein meals.

medications (i.e., H2-blockers) to decrease gastric acid production in the stomach.

Acute pancreatitis is self-limiting, meaning it usually resolves on its own over time. Up to 90 percent of individuals recover from acute pancreatitis without any complications. Chronic pancreatitis may also be self-limiting, but may resolve after several attacks and with a greater risk of developing long-term problems such as diabetes, chronic pain, diarrhea, ascites, biliary cirrhosis, bile duct obstruction, or pancreatic cancer.

Pancreatic Cancer

What is pancreatic cancer?

Pancreatic cancer is the fourth most common cancer in men and women in the US. According to the American Cancer Society, it is estimated that there will be 32,180 new cases of pancreatic cancer in 2005, and 31,800 deaths are expected. Pancreatic cancer occurs when malignant cells grow out of control.

What is a risk factor?

A risk factor is anything that may increase a person's chance of developing a disease. It may be an activity, such as smoking, diet, family history, or many other things. Different diseases, including cancers, have different risk factors.

Although these factors can increase a person's risk, they do not necessarily cause the disease. Some people with one or more risk factors never develop the disease, while others develop disease and have no known risk factors.

But, knowing your risk factors to any disease can help to guide you into the appropriate actions, including changing behaviors and being clinically monitored for the disease.

Risk factors for pancreatic cancer, according to the National Cancer Institute, include:

age - most pancreatic cancer occurs in people over the age of 60.

smoking - cigarette smokers are two or three times more likely than non-smokers to develop pancreatic cancer.

diabetes - pancreatic cancer occurs more often in people who have diabetes than in those who do not.

being male - more men than women are diagnosed with pancreatic cancer.

being African American - African Americans are more likely than Asians, Hispanics, or Caucasians to be diagnosed with pancreatic cancer.

family history - the risk for developing pancreatic cancer triples if a person's mother, father, or a sibling had the disease.

chronic pancreatitis - this condition of the pancreas has been linked with increased risk for pancreatic cancer.

There are several types of pancreatic cancers, including the following:

adenocarcinoma of the pancreas - the most common pancreatic cancer, which occurs in the lining of the pancreatic duct.

cystadenocarcinoma - a rare pancreatic cancer.

acinar cell carcinoma - a rare pancreatic cancer.

Some benign (non-cancerous) tumors in the pancreas include the following:

insulinoma - a rare pancreatic tumor that secretes insulin, the hormone that lowers glucose levels in the blood.

gastrinoma - a tumor that secretes above average levels of gastrin, a hormone which stimulates the stomach to secrete acids and enzymes. Gastrinoma can cause peptic ulcers.

glucagonoma - a tumor that secretes glucagon, a hormone which raises levels of glucose in the blood, leading to a rash.

What are the symptoms of pancreatic cancer?

The following are the other most common symptoms of pancreatic cancer. However, each individual may experience symptoms differently. Symptoms may include:

pain in the upper abdomen or upper back

loss of appetite

weight loss

jaundice (yellow skin and eyes, and dark urine)

indigestion

nausea

vomiting

The symptoms of pancreatic cancer may resemble other conditions or medical problems. Always consult your physician for a diagnosis.

How is pancreatic cancer diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for pancreatic cancer may include the following:

ultrasound (Also called sonography.) - a diagnostic imaging technique that uses high-frequency sound waves to create an image of the internal organs. Ultrasounds are used to view internal organs of the abdomen such as the liver, pancreas, spleen, and kidneys and to assess blood flow through various vessels. The ultrasound may be performed using and external or internal device:

transabdominal ultrasound - the physician places an ultrasound device on the abdomen to create the image of the pancreas.

endoscopic ultrasound (EUS) - the physician inserts an endoscope, a small, flexible tube with an ultrasound device at the tip, through the mouth and stomach, and into the small intestine. As the physician slowly withdraws the endoscope, images of the pancreas and other organs are made.

computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

endoscopic retrograde cholangiopancreatography (ERCP) - a procedure that allows the physician to diagnose and treat problems in the liver, gallbladder, bile ducts, and pancreas. The procedure combines x-ray and the use of an endoscope - a long, flexible, lighted tube. The scope is guided through the patient's mouth and throat, then through the esophagus, stomach, and duodenum. The physician can examine the inside of these organs and detect any abnormalities. A tube is then passed through the scope, and a dye is injected which will allow the internal organs to appear on an x-ray.

percutaneous transhepatic cholangiography (PTC) - a needle is introduced through the skin and into the liver where the dye (contrast) is deposited and the bile duct structures can be viewed by x-ray.

pancreas biopsy - a procedure in which a sample of pancreatic tissue is removed (with a needle or during surgery for examination under a microscope.

special blood tests

positron emission tomography (PET) - a type of nuclear medicine procedure. This means that a tiny amount of a radioactive substance, called a radionuclide (radiopharmaceutical or radioactive tracer), is used during the procedure to assist in the examination of the tissue under study. Specifically, PET studies evaluate the metabolism of a particular organ or tissue, so that information about the physiology (functionality) and anatomy (structure) of the organ or tissue is evaluated, as well as its biochemical properties. Thus, PET may detect biochemical changes in an organ or tissue that can identify the onset of a disease process before anatomical changes related to the disease can be seen with other imaging processes such as computed tomography (CT) or magnetic resonance imaging (MRI).

Treatment for pancreatic cancer:

Specific treatment for pancreatic cancer will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

type of cancer

your tolerance of specific medicines, procedures, or therapies

expectations for the course of the disease

your opinion or preference

Treatment may include:

surgery - Surgery may be necessary to remove the tumor - a section or entire pancreas and/or the small intestine. The type of surgery depends on the stage of the cancer, the location and size of the tumor, and the person’s health. Types of surgery for pancreatic cancer include the following:

Whipple procedure - if the tumor is located at the head of the pancreas (the widest part), the head of the pancreas, part of the small intestine, bile duct, and stomach, and other tissues will be removed.

distal pancreatectomy - if the tumor is located in the body and tail of the pancreas, both of these sections of the pancreas will be removed, along with the spleen.

total pancreatectomy - the entire pancreas, part of the small intestine and stomach, the common bile duct, the spleen, the gallbladder, and some lymph nodes will be removed.

external radiation (external beam therapy) - a treatment that precisely sends high levels of radiation directly to the cancer cells. The machine is controlled by the radiation therapist. Since radiation is used to kill cancer cells and to shrink tumors, special shields may be used to protect the tissue surrounding the treatment area. Radiation treatments are painless and usually last a few minutes. Radiation therapy may be given alone, or in combination with surgery and chemotherapy.

chemotherapy - the use of anticancer drugs to treat cancerous cells. In most cases, chemotherapy works by interfering with the cancer cell’s ability to grow or reproduce. Different groups of drugs work in different ways to fight cancer cells. The oncologist will recommend a treatment plan for each individual. Chemotherapy may be given alone, or in combination with surgery and radiation therapy.

medication (to relieve or reduce pain)

Long-term prognosis for individuals with pancreatic cancer depends on the size of the tumor, lymph node involvement, and degree of metastases (spreading) at the time of diagnosis.

Pseudocysts of the Pancreas

What are pseudocysts of the pancreas?

Pseudocysts of the pancreas are abnormal collections of fluid, dead tissue, pancreatic enzymes, and blood that can lead to a painful mass in the pancreas. Pseudocysts usually develop several weeks after an episode of acute pancreatitis (a sudden, painful inflammation of the pancreas). Alcoholism also contributes to the risk of pseudocysts of the pancreas. Other, more rare causes include abdominal trauma and gallbladder disease.

What are the symptoms of pseudocysts of the pancreas?

The following are the most common symptoms of pseudocysts of the pancreas. However, each individual may experience symptoms differently. Symptoms may include:

abdominal pain

nausea

vomiting

poor appetite

weight loss

diarrhea

fever

detectable, tender mass in the abdomen

jaundice - yellowing of the skin and eyes.

ascites - fluid build-up in the abdominal cavity.

The symptoms of pseudocysts of the pancreas may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

How are pseudocysts of the pancreas diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for pseudocysts of the pancreas may include the following:

blood tests

chest x-ray - a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.

computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure using a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

ultrasound (Also called sonography.) - a diagnostic imaging technique, which uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs of the abdomen such as the liver, spleen, and kidneys and to assess blood flow through various vessels.

endoscopic retrograde cholangiopancreatography (ERCP) - a procedure that allows the physician to diagnose and treat problems in the liver, gallbladder, bile ducts, and pancreas. The procedure combines x-ray and the use of an endoscope - a long, flexible, lighted tube. The scope is guided through the patient's mouth and throat, then through the esophagus, stomach, and duodenum. The physician can examine the inside of these organs and detect any abnormalities. A tube is then passed through the scope, and a dye is injected which will allow the internal organs to appear on an x-ray.

Treatment for pseudocysts of the pancreas:

Specific treatment for pseudocysts of the pancreas will be determined by your physician based on:

your age, overall health, and medical history

extent of the disease

your tolerance of specific medicines, procedures, or therapies

expectations for the course of the disease

your opinion or preference

The goal for treatment of a pancreatic pseudocyst is to monitor its growth and to treat surgically if it grows, or if there is risk for complications.

Treatment may include:

close monitoring by scans (to determine any change in size)

surgical drainage of the cyst(s)

If left untreated or unmonitored, pseudocysts can rupture, causing extreme pain, blood loss, and infection.

Gallstones

Introduction

Gallstones are solid deposits of cholesterol or calcium salts that form in your gallbladder or nearby bile ducts. They often cause no symptoms and require no treatment. But some people with gallstones have a gallbladder attack that can cause symptoms, such as nausea and an intense, steady ache in their upper middle or upper right abdomen. In some cases, the pain can be severe and intermittent.

You're at greater risk of developing gallstones if you're older, female or overweight. Rapid weight loss or eating a very low calorie diet also can put you at risk of gallstones.

Complications from gallstones can be serious, and even fatal, if left untreated. Fortunately, treatment for gallstones is usually straightforward, and newer techniques often allow faster recovery time.

Signs and symptoms

You may not know you have gallstones until they're discovered during tests done for other reasons. But sometimes gallstones may cause certain signs and symptoms. Gallstone symptoms include:

· Chronic indigestion. Signs and symptoms of indigestion may include nausea, gas, bloating and sometimes abdominal pain. These signs and symptoms may occur or be made worse after you eat high-fat foods. But even if you have gallstones, they often aren't the cause of your digestive problems. A number of other conditions - including gastroesophageal reflux disease (GERD) and peptic ulcers of the stomach or small intestine (duodenum), or irritable bowel syndrome - also can cause chronic indigestion. For that reason, it's important to discuss your symptoms carefully with your doctor.

· Upper abdominal pain. Sudden, steady and moderate to intense pain in your upper middle or upper right abdomen may signal a gallbladder attack. The pain may occur one to two hours after eating but may also occur at other times - even at night. It can last about 30 minutes to several hours. Gallbladder pain usually starts in your upper middle or upper right abdomen and, on occasion, may shift to your back or right shoulder blade. After the pain subsides, you might have a mild aching or soreness in your upper abdomen that can last for up to a day or so. If you've had one gallbladder attack, the odds are about seven in 10 that you'll have additional attacks.

· Nausea and vomiting. These signs and symptoms may accompany a gallbladder attack.

· Fever. Gallstones sometimes get trapped in the neck of the gallbladder and can cause persistent pain that lasts more than several hours and is accompanied by fever. If you experience this type of persistent pain or you have a fever with the pain, seek medical attention right away.

Symptoms of bile duct obstruction

Sometimes small gallstones escape the gallbladder and enter the duct leading from your liver and gallbladder to your small intestine (common bile duct). They may also occasionally enter the duct leading to your pancreas. In some cases, a stone may block this duct - a condition called pancreatitis, which can be fatal if you don't receive treatment. You'll likely have pain and sometimes fever due to inflammation at or near the site of the blockage. Other signs and symptoms of bile duct obstruction include:

· Yellowing of your skin and the whites of your eyes (jaundice)

· Clay-colored stools

· Fever

If you experience any of these signs and symptoms, seek medical treatment right away. Keep in mind that sometimes you may have jaundice and changes in the color of your urine or stools without also having much pain or indigestion.

Your liver produces bile - a greenish-brown fluid composed of bile salts, fatty compounds, cholesterol and other chemicals. This fluid is concentrated and stored in your gallbladder you need it to help digest fats in your small intestine.

When you eat, your gallbladder contracts and releases bile through the cystic duct and into the common bile duct. The common bile duct then carries bile to the upper part of your small intestine (duodenum), where it begins to help break down the fat in your food. But if bile within your gallbladder becomes chemically unbalanced, it can form into particles that eventually grow into stones.

Gallstones can be as small as a grain of sand or as large as a golf ball and may be smooth and round or irregular with a number of edges. You can have just one stone or hundreds of them.

Types of gallstones

No matter what their size, shape or number, gallstones generally fall into one of two categories:

· Cholesterol gallstones. These gallstones, often yellow in color, are composed mainly of undissolved cholesterol, although they can also have other components, such as calcium and bilirubin, the residue from the breakdown of red blood cells. About 80 percent of gallstones are cholesterol stones.

· Pigment gallstones. These small, dark brown or black stones form when your bile contains too much bilirubin. It's not always clear what causes them. They tend to form in people with conditions - such as cirrhosis, biliary tract infection and sickle cell anemia - that result in excess bilirubin forming.

Contributors to gallstones

Many factors, some of which aren't well understood, contribute to the formation of gallstones. They include:

· Too much cholesterol. Normally, your bile contains enough bile salts and lecithin - a fatty compound - to dissolve the cholesterol excreted by your liver. But if your bile contains more cholesterol than can be dissolved, the cholesterol may form into crystals and eventually into stones. Cholesterol in your bile has no relation to the levels of cholesterol in your blood, and cholesterol-lowering drugs don't help prevent gallstones.

· Incomplete or infrequent gallbladder emptying. If your gallbladder doesn't empty completely or often enough, bile may become too concentrated and contribute to the formation of gallstones. This may occur during pregnancy. Eating too little fat or going long periods without eating, such as skipping breakfast, also can decrease gallbladder contractions. Fewer contractions can keep the gallbladder from emptying completely or frequently.

Your gallbladder is a pear-shaped sac about 3 inches long that's tucked just below your liver on your right side. It serves as a reservoir for bile produced by your liver. Bile is a greenish-brown fluid that helps digest fats. After you eat, your gallbladder contracts and empties bile into your small intestine (duodenum). Gallstones are made up of various components of bile. Most are made up, in part at least, of crystallized cholesterol. These are often yellow in color.

Risk factors

Gallstones tend to run in families. Other factors that may increase your risk include:

· Sex. Women between the ages of 20 and 60 are about three times as likely as men are to have gallstones. That's because the female hormone estrogen causes more cholesterol to be excreted in bile. Pregnancy, which causes estrogen levels to rise, also increases the risk. In addition, birth control pills and hormone therapy (HT) both increase bile cholesterol levels and decrease gallbladder emptying. If you take these medications and are concerned about gallstones, talk to your doctor.

· Body weight. As your body mass index (BMI) - a method of estimating your percentage of body fat using your height and weight - increases, so does your risk of developing gallstones. Being even moderately overweight increases cholesterol in your bile. It also decreases bile salts and reduces the frequency with which your gallbladder contracts and empties.

· Diet. Low-calorie, rapid-weight-loss diets tend to disrupt your bile chemistry and may cause your gallbladder to contract less often. This makes it more likely you'll develop gallstones. In fact, losing more than 3 pounds a week may increase your risk of developing gallstones when compared with losing weight more gradually.

People who undergo gastrointestinal surgery to lose weight rapidly, also called bariatric surgery, are at increased risk of gallstones. As many as one in three people who have bariatric surgery may develop symptomatic gallstones a few months after surgery.

· Age. Your chance of developing gallstones increases with age. People older than 60 years of age are more likely to have gallstones than are those who are younger.

· Ethnicity. American Indians have the highest incidence of gallstones in the United States. Mexican-Americans also are at increased risk.

Screening and diagnosis

Many gallstones, especially those that don't cause signs or symptoms, are discovered during tests - including ultrasounds or computerized tomography scans - done for other reasons.

If you have signs or symptoms of gallstones, your doctor is likely to suspect them based on your medical history and a physical exam. During the exam, he or she will check for jaundice of your skin or the whites of your eyes and will feel (palpate) your abdomen to see if it's tender.

If your doctor suspects gallstones, you may have a blood test to check for signs of infection (shown by an elevated white blood cell count), abnormal levels of liver or pancreatic enzymes, or excess bilirubin.

You may also undergo these diagnostic tests:

· Ultrasonography. An ultrasound test uses sound waves rather than X-rays to display an image of the organs in your abdomen, including your gallbladder. It's often the best way to detect gallstones in your gallbladder and sometimes in the common bile duct.

· Computerized tomography (CT) scan. A CT scan is a diagnostic imaging procedure that uses a series of computer-generated X-rays to provide a comprehensive view of your internal organs.

· Radionuclide scan (cholescintigraphy, HIDA scan). In this test, you'll receive a small amount of a radioactive tracer material through your veins (intravenously), followed by a scan of the gallbladder to see if the tracer material gains access to the gallbladder. If it doesn't, a stone is likely blocking the opening of the gallbladder or cystic duct.

· Endoscopic retrograde cholangiopancreatography (ERCP). Your doctor may perform this procedure to help locate and remove stones in the ducts. During ERCP, a flexible, lighted viewing instrument (endoscope) is gently passed down your throat, through your stomach and into the upper part of your small intestine (duodenum). Air is used to inflate your intestinal tract so that your doctor can more easily see the openings of the bile and pancreatic ducts. Then, a dye is injected into these ducts through a tiny hollow tube (cannula) that's passed through the endoscope. Finally, X-rays are taken of the ducts.

If a stone is blocking one of the ducts, a specialized kind of cutting instrument may be inserted through the endoscope to try to remove the stone. A less invasive alternative called magnetic resonance cholangiopancreatography is used in some medical centers to diagnose blocked bile ducts. However, this technique doesn't allow for the removal of the stone during the procedure.

· Endoscopic ultrasound (EUS). In some cases, your doctor may use this technique to help diagnose stones in the common bile duct. In this procedure, an ultrasound transducer is placed on the tip of an endoscope, which is then gently passed down your throat and through your stomach. Because the ultrasound instrument is closer to the bile ducts, it provides clearer and more accurate images than does traditional ultrasound. EUS is a less invasive and complex procedure than is ERCP, but if any stones need to be removed, your doctor will still need to perform an ERCP.

Complications

Complications of gallstones may include:

· Blockage of the common bile duct. In some cases, gallstones can block the ducts that lead from your gallbladder, liver or pancreas to your small intestine. The signs and symptoms of common bile duct obstruction include yellowing of the whites of the eyes and skin (jaundice), dark urine, and pain in the upper abdomen. If you also have fever and chills, you may have an underlying complication such as an inflamed gallbladder (cholecystitis) or an infection in your bile duct (cholangitis).

· Inflammation of the pancreas. An obstruction in the common bile duct near the junction with the pancreatic duct can also cause a blockage in the pancreatic duct or inflammation of the pancreas (acute pancreatitis). In many people the common duct and the pancreatic duct empty into the duodenum at a common opening.

Pancreatitis is likely to cause an intense, constant pain in your upper abdomen that may radiate to your back or chest. The pain is usually worse when you lie flat and better when you sit up or bend forward. You may not be able to pass gas, and your abdomen may be tender and distended. Sometimes, you may also have nausea, vomiting and fever. In mild cases, symptoms usually subside within a few days to a week, but severe acute pancreatitis can be life-threatening.

· Gallbladder cancer. People with gallstones are also more likely to develop gallbladder cancer. Researchers speculate that gallstones may cause your gallbladder to release bile more slowly, which increases inflammation and the amount of time cells are exposed to cancer-causing substances in the bile. However, gallbladder cancer is rare and the vast majority of people with gallstones never develop gallbladder cancer.

Pancreatitis often is caused by gallstones leaving the gallbladder and lodging near the pancreatic duct, obstructing the duct. This can cause digestive juices produced by the pancreas to move into the pancreas tissue itself, causing potentially severe damage.

Treatment

Because the majority of gallstones produce no symptoms, they require no treatment. Doctors often discover these "silent stones" during routine medical checkups or exams for other illnesses and usually recommend taking a wait-and-see approach to treatment. If your gallstones cause symptoms, however, several possible treatments are available.

Surgery
Removing the gallbladder is the preferred treatment for the majority of people who have gallstones that cause symptoms. In fact, gallbladder surgery (cholecystectomy) is one of the most common surgeries performed in the United States. The surgery can be performed in two ways:

· Laparoscopic surgery. Most often gallbladder surgery is performed using a laparoscope, a pencil-thin tube with its own lighting system and miniature video camera. A surgeon inserts the laparoscope into your abdomen through a hollow instrument (cannula). Only small incisions are required. The video camera then produces a magnified view on a television monitor of the inside of your abdomen. This allows the surgeon to see the surgery in detail. To remove your gallbladder, he or she uses tiny instruments inserted through several other small abdominal incisions.

Because laparoscopic cholecystectomy uses smaller incisions, you'll likely have less postoperative pain, less scarring and an earlier return to your normal activity - often within just a few days. Laparoscopic removal of the gallbladder is effective in the majority of cases. Occasionally, although your surgeon planned on a laparoscopic approach, the surgery may need to be converted to an open surgery for technical reasons.

· Open surgery. In open surgery, the gallbladder is removed through a large abdominal incision. Your doctor may regard this surgery as the best option in severe cases. It may also be used when the gallbladder walls are thick and hard, the gallbladder is obviously infected, or there is scar tissue from earlier abdominal operations. Recovery from open surgery typically entails up to a week's stay in the hospital, followed by several weeks at home.

If you have stones in the bile duct as well as your gallbladder, your doctor may recommend surgical removal of both the duct stones and your gallbladder. But in some cases, your doctor may suggest removing the stones in the bile duct using an endoscope (ERCP). If you have ERCP, your gallbladder also may be removed at a later date. Often, a cutting instrument is inserted through the endoscope, and the entrance of the bile duct is enlarged so the stone can pass through it. The same procedure may be used to remove a stone from a blocked pancreatic duct.

After surgery

Your liver will continue to produce enough bile to digest a normal diet after you have surgery. But you may notice you're having more bowel movements than usual and that their consistency is less solid. These symptoms usually lessen over time. However, chronic diarrhea may be a continuing problem for about 1 percent of people who've had their gallbladder removed.

When diarrhea remains a problem, general self-care measures - such as avoiding dairy products, fats and spicy foods as well as adding more fiber to your diet - may help. If diarrhea persists, see your doctor, because medications can sometimes help.

Nonsurgical options

Stones usually recur when nonsurgical treatments are used. However, when surgery isn't the best option, your doctor may recommend one of the following gallstone treatment options:

· Bile salt tablets. Your doctor may have you take the medication ursodiol (Actigall), which dissolves cholesterol stones over a period of time. The treatment works best on small cholesterol stones, but is only effective about 50 percent of the time. To prevent a recurrence, most people need to take the medication for years or longer.

· Sound wave therapy (extracorporeal shock wave lithotripsy). This treatment uses high-frequency sound waves to break up gallstones. You then take ursodiol tablets to dissolve the fragments. Sound wave therapy is appropriate for only a small percentage of people with gallstones. If you have more than one stone, your stone is large, or you have acute cholecystitis or cholangitis, you're probably not a good candidate for this treatment. And, as with other nonsurgical therapies, your gallstones are likely to return unless you take ursodiol indefinitely.

· Percutaneous electrohydraulic lithotripsy. This procedure relies on a catheter that's inserted into the gallbladder several weeks prior to the treatment. A small probe is inserted into the catheter to deliver short bursts of energy to break up the stones. This is the only nonsurgical treatment option that can be used on any type of gallstone, including pigment stones. Because this procedure is time-consuming and isn't widely available, it's usually considered only for people with a high risk of surgical complications, such as people with heart disease.

· Topical gallstone dissolution. In this procedure, a small catheter is inserted into the gallbladder. A solution that dissolves cholesterol gallstones is then delivered through the catheter into the gallbladder over a several hour period. This option has lower recurrence rates than medication, but it's still considered experimental and isn't widely available.

Prevention

Although you can't entirely prevent gallstones from forming, you may be able to lower your risk by following these suggestions:

· Maintain a healthy body weight. If you need to lose weight, experts recommend losing no more than 1/2 to 2 pounds a week.

· Avoid crash diets or a very low intake of calories - less than 800 calories a day.

· Be active. Make sure that you exercise regularly.

· Choose a low-fat, high-fiber diet that emphasizes fresh fruits, vegetables and whole grains. Reduce the amount of animal fat, butter, margarine, mayonnaise and fried foods you eat.

Common Liver Function Tests

What are some of the most common liver function tests?

A series of special blood tests can often determine whether or not the liver is functioning properly. These tests can also distinguish between acute and chronic liver disorders and between hepatitis and cholestasis.

The most commonly performed blood tests include the following:

serum bilirubin test

This test measures the levels of bilirubin in the blood. Bilirubin is produced by the liver and is excreted in the bile. Elevated levels of bilirubin may indicate an obstruction of bile flow or a problem in the processing of bile by the liver.

serum albumin test

This test is used to measure the level of albumin (a protein in the blood) and aides in the diagnosis of liver disease.

serum alkaline phosphatase test

This test is used to measure the level of alkaline phosphatase (an enzyme) in the blood. Alkaline phosphatase is found in many tissues, with the highest concentrations in the liver, biliary tract, and bone. This test may be performed to assess liver functioning and to detect liver lesions that may cause biliary obstruction, such as tumors or abscesses.

serum aminotransferases (transaminases)

This enzyme is released from damaged liver cells.

prothrombin time (PTT) test

The prothrombin time test measures how long it takes for blood to clot. Blood clotting requires vitamin K and a protein that is made by the liver. Prolonged clotting may indicate liver disease or other deficiencies in specific clotting factors.

alanine transaminase (ALT) test

This test measures the level of alanine aminotransferase (an enzyme found predominantly in the liver) that is released into the bloodstream after acute liver cell damage. This test may be performed to assess liver function, and/or to evaluate treatment of acute liver disease, such as hepatitis.

aspartate transaminase (AST) test

This test measures the level of aspartate transaminase (an enzyme that is found in the liver, kidneys, pancreas, heart, skeletal muscle, and red blood cells) that is released into the bloodstream after liver or heart problems.

gamma-glutamyl transpeptidase test

This test measures the level of gamma-glutamyl transpeptidase (an enzyme that is produced in the liver, pancreas, and biliary tract). This test is often performed to assess liver function, to provide information about liver diseases, and to detect alcohol ingestion.

lactic dehydrogenase test

This test can detect tissue damage and aides in the diagnosis of liver disease. Lactic dehydrogenase is a type of protein (also called an isoenzyme) that is involved in the body's metabolic process.

5'-nucleotidase test

This test measures the levels of 5'- nucleotidase (an enzyme specific to the liver). The 5'- nucleotidase level is elevated in persons with liver diseases, especially those diseases associated with cholestasis (disruption in the formation of, or obstruction in the flow of bile).

alpha-fetoprotein test

Alpha-fetoprotein (a specific blood protein) is produced by fetal tissue and by tumors. This test may be performed to monitor the effectiveness of therapy in certain cancers, such as hepatomas.

mitochondrial antibodies test

The presence of these antibodies can indicate primary biliary cirrhosis, chronic active hepatitis, and certain other autoimmune disorders.