Differential ndiagnosis of acute viral hepatitis n(A, B, C, D, E, mixed-hepatitis), the role and use of different diagnostic nmethods, evaluation. Acute hepatic encephalopathy. Features of diagnosis and treatment of fulminant forms of viral hepatitis
The term viral hepatitis ncan describe either a clinical illness or the histologic findings associated nwith the disease. Acute infection with a hepatitis virus may result iconditions ranging from subclinical disease to self-limited symptomatic disease nto fulminant hepatic failure. Adults with acute hepatitis A or B are usually nsymptomatic. Persons with acute hepatitis C may be either symptomatic or nasymptomatic (ie, subclinical).
Typical symptoms of acute nhepatitis are fatigue, anorexia, nausea, and vomiting. Very high naminotransferase values (>1000 U/L) and hyperbilirubinemia are often observed. Severe ncases of acute hepatitis may progress rapidly to acute liver failure, marked by poor hepatic nsynthetic function. This is often defined as a prothrombin time (PT) of 16 nseconds or an international normalized ratio (INR) of 1.5 in the absence of nprevious liver disease.
Fulminant hepatic nfailure (FHF) is defined as acute liver failure that is complicated by hepatic nencephalopathy. In contrast to the encephalopathy associated with cirrhosis, nthe encephalopathy of FHF is attributed to increased permeability of the nblood-brain barrier and to impaired osmoregulation in the brain, which leads to nbrain-cell swelling. The resulting brain edema is a potentially fatal ncomplication of fulminant hepatic failure.
FHF may occur in as many nas 1% of cases of acute hepatitis due to hepatitis A or B. Hepatitis E is a ncommon cause in Asia; whether hepatitis C is a cause remains controversial. Although nFHF may resolve, more than half of all cases result in death unless liver transplantation is performed in time.
Providing that acute viral nhepatitis does not progress to FHF, many cases resolve over a period of days, nweeks, or months. Alternatively, acute viral hepatitis may evolve into chronic nhepatitis. Hepatitis A and hepatitis E never progress to chronic hepatitis, neither clinically or histologically.
Histologic evolution to nchronic hepatitis can be demonstrated in approximately 90-95% of cases of acute nhepatitis B ieonates, 5% of cases of acute hepatitis B in adults, and as nmany as 85% of cases of acute hepatitis C. Some patients with chronic hepatitis nremain asymptomatic for their entire lives. Other patients report fatigue n(ranging from mild to severe) and dyspepsia.
Approximately 20% of npatients with chronic hepatitis B or hepatitis C eventually develop cirrhosis, as evidenced by the nhistologic changes of severe fibrosis and nodular regeneration. Although some npatients with cirrhosis are asymptomatic, others develop life-threatening ncomplications. The clinical illnesses of chronic hepatitis and cirrhosis may ntake months, years, or decades to evolve.
Hepatitis A (VHA)
http://www.emedicinehealth.com/hepatitis_a/article_em.htm
Agent was first discovered in 1973 by Feinstone. This is nRNA-containing virus. Complete viral bodies as well as empty parts (capsules) nwith size of 27-30 nm can be noticed under electronic microscope. On their nsurfaces capsomeres are seen. Nucleopeptide of VHA(Fig.1) does not possess nsurface projections and covering. Core structure is not revealed in the virion. n
Virus contains n4 peptides (VP1-4), participating in reactions of immune precipitation. It is nassumed that VP1 and VP3 are located pertly on the surface and VP2 and VP4 are npresent inside the virion. However, up till date, there is not authentic ninformations about their meaning in relation to antiqenicity and nimmunogenicity.
Hepatitis A nvirus. Electronic microscopy (negative contrast)
Virus of nhepatitis A may reproduce iumber of human and monkey cellular cultures, from nwhere viral antigen is obtained. It is necessary to remark, that successful nadaptation of VHA towards culture of cells is very much necessary for study of nbiological properties, for obtaining of source of reagents for diagnostics n(antigen, antiserum), as well as for construction of vaccines, (live, killed).
Hepatitis A (formerly known as infectious hepatitis) is an acute infectious ndisease of the liver ncaused by the hepatitis A virus (HAV), an RNA virus, usually spread by the nfecal-oral route, transmitted person-to-person by ingestion of contaminated nfood or water or through direct contact with an infectious person. Tens of nmillions of individuals worldwide are estimated to become infected with HAV neach year. The time between infection and the appearance of the symptoms (the incubation period) is nbetween two and six weeks and the average incubation period is 28 days.
In developing ncountries, and in regions with poor hygiene standards, the incidence of infection with this virus is high and the illness nis usually contracted in early childhood. As incomes rise and access to cleawater increases, the incidence of HAV decreases. Hepatitis A infection causes nno clinical signs and symptoms in over 90% of infected children and since the ninfection confers lifelong immunity, the disease is of no special significance nto those infected early in life. In Europe, the United States, and other nindustrialized countries on the other hand, the infection is contracted nprimarily by susceptible nyoung adults, most of whom are infected with the virus during trips to ncountries with a high incidence of the disease or through contact with ninfectious persons.
HAV infection produces a nself-limited disease that does not result in chronic infection or chronic liver ndisease. However, 10–15% of patients might experience a relapse of symptoms nduring the 6 months after acute illness. Acute liver failure from hepatitis A nis rare (overall case-fatality rate: 0.5%). The risk for symptomatic infectiois directly related to age, with more than 80% of adults having symptoms ncompatible with acute viral hepatitis and the majority of children having neither asymptomatic or unrecognized infection. Antibody produced in response to nHAV infection persists for life and confers protection against reinfection. The ndisease can be prevented by vaccination, nand hepatitis nA vaccines have been proven effective in controlling outbreaks nworldwide.
Hepatitis B (VHB)
http://www.emedicinehealth.com/hepatitis_b/article_em.htm
VHB iatural condition is revealed in sick people and carriers, iforest marmots, in carth squirrels, in Peiking ducks. This DHA-containing virus n(Fig.2) is pathogenic for human and few types of primates – chimpanzee, ngorillas. VHB causes acute and persistent infection, primarily damages liver.
Virus consists of nucleus and covering. Further antigenic structure of nVHB is differentiated: HBsAg – surface, HBcAg – internal (care), HBeAg – reflects infectiouness of virus.
Towards these antigens in organism of patients antibodies are nproduced: anti-HBs; anti-HBc; anti-HBe.
Presence of HBsAg in human organism testifies the presence of nacute and latent proceeding infection. It is assumed, that nprolonged conservation HbsAg in serum of nthe blood in sick man may testify nabout transfer of the process into chronic nform. HBsAg is revealed in majority of patients in incubation stage. nHBcAg is practically not determined in blood and fixed in directly by nDNA-polymerize reactions, falling positive in acute period of disease, as well nas after many months and years in carriers. Soon after discovery of HBsAg iblood of patients anti-HBc appear. Most often they are observed in carriers of ninfection. In early stages of disease HBeAg is revealed, which is then changed nby anti-HBe.
Very important ndiagnostic information may be obtained by using methods of determination of DNA nHB. For this purpose molecular hybridization of nucleic acids and polymerize nchain reaction (PCR) is used. Genospecific viral DNA is observed in serum of nblood, in bioptates of liver, in lymphocytes of peripheral blood. nMentioned method enables to discover very small quantities of viral DNA iinvestigated samples, which moderately increases reliability of diagnosis.
Electronic microscopy (negative contrast) hepatitis nvirus B
Hepatitis C (VHC)
http://www.nlm.nih.gov/medlineplus/hepatitisc.html
Hepatitis C is an infectious ndisease affecting primarily the liver, caused by the hepatitis C virus n(HCV). The infection is often asymptomatic, but nchronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is ngenerally apparent after many years. In some cases, those with cirrhosis will ngo on to develop liver nfailure, liver cancer or life-threatening esophageal nand gastric nvarices.
HCV is spread primarily by blood-to-blood contact nassociated with intravenous drug use, poorly sterilized medical equipment and transfusions. nAn estimated 150–200 million people worldwide are infected with hepatitis C. The existence of hepatitis C (originally identifiable only as a type of non-A non-B hepatitis) was npostulated in the 1970s and proven in 1989. Hepatitis C ninfects only humans and chimpanzees. n
The virus persists in the liver in about 85% of those ninfected. This persistent infection can be treated with medication: the nstandard therapy is a combination of peginterferon and ribavirin, with either nboceprevir or telaprevir added isome cases. Overall, 50–80% of people treated are cured. Those who develop ncirrhosis or liver cancer may require a liver transplant. Hepatitis C is the leading reason for liver ntransplantation, though the virus usually recurs after transplantation.[7] No vaccine against hepatitis C is available.
Virion of virus of hepatitis C consists of nucleus and lipid external nmembrane. Genome is represented by single chain RNA. VHC is heavily resistant nin external medium, particularly in biological fluids such as preparations of nblood, sperm and others. It is sensitive to chloroform, to other ndesinfective solutions and high temperatures (100 °C and more).
Antigenic nstructure of VHC is less studied. It is established, that to the antibodies are nproduced (class Ig M and G) to virus in the organism of the patient. Their ndiscovery in blood serum of patient testifies presence of acute or chronic ndisease. Antibodies may stick to definite level during 6-9 months, and nthereafter their titers in serum decrease upto complete disappearance.
Electron micrograph of hepatitis C virus purified from cell nculture (scale = 50 nanometers)
The hepatitis nC virus (HCV) is a small, enveloped, single-stranded, positive-sense nRNA virus. It is a nmember of the Hepacivirus ngenus in the family Flaviviridae. nThere are seven major genotypes of HCV, which are known as genotypes one to nseven. The genotypes are divided into several subtypes with the number of nsubtypes depending on the genotype. In the United States, about 70% of cases nare caused by genotype 1, 20% by genotype 2 and about 1% by each of the other ngenotypes. Genotype 1 is also the most common in South America and Europe.
The half life of the virus nparticles in the serum is around 3 hours and may be as short as 45 minutes. nIn an infected person, about 1012 virus particles are produced neach day. In addition to replicating in the liver the virus can multiply ilymphocytes.
Transmission
The primary route of transmission in the developed world is intravenous drug use (IDU), while in the developing world the nmain methods are blood ntransfusions and unsafe medical procedures. The cause of ntransmission remains unknown in 20% of cases; however, many of these are nbelieved to be accounted for by IDU.
Intravenous drug use
IDU is a major risk factor nfor hepatitis C in many parts of the world. Of 77 ncountries reviewed, 25 (including the United States) were found to have nprevalences of hepatitis C in the intravenous drug nuser population of between 60% and 80%. Twelve countries had rates greater tha80%. It is believed that ten million intravenous drug users are infected with hepatitis C; China (1.6 million), the United States n(1.5 million), and Russia (1.3 million) have the highest absolute ntotals. Occurrence of hepatitis C among prisoinmates in the United States is 10 to 20 times that of the occurrence observed nin the general population; this has been attributed to high-risk behavior iprisons such as IDU and tattooing with nonsterile equipment.
Healthcare exposure
Blood ntransfusion, transfusion of blood products, or organ transplants nwithout HCV screening carry significant risks of infection. The United States ninstituted universal screening in 1992 and Canada instituted universal nscreening in 1990. This decreased the risk from one in 200 units to between one nin 10,000 to one in 10,000,000 per unit of blood. This low risk remains as nthere is a period of about 11–70 days between the potential blood donor’s nacquiring hepatitis C and the blood’s testing positive depending on the method. nSome countries do not screen for hepatitis C due to the cost.
Those who have experienced a needle nstick injury from someone who was HCV positive have about a 1.8% nchance of subsequently contracting the disease themselves. The risk is greater nif the needle in question is hollow and the puncture wound is deep. There is a nrisk from mucosal exposures to blood; but this risk is low, and there is no nrisk if blood exposure occurs on intact skin.
Hospital equipment has also nbeen documented as a method of transmission of hepatitis C, nincluding reuse of needles and syringes; multiple-use medication vials; infusiobags; and improperly sterilized surgical equipment, among others. Limitations nin the implementation and enforcement of stringent standard precautions ipublic and private medical and dental facilities are known to be the primary ncause of the spread of HCV in Egypt, nthe country with highest rate of infection in the world.
Sexual intercourse
Whether hepatitis C can be transmitted through sexual activity is ncontroversial. While there is an association between high-risk sexual activity nand hepatitis C, and multiple sexual partners are a risk factor for hepatitis nC, there is no conclusive evidence that hepatitis C can be transmitted by nsexual activity, since people who report transmission with sex as their only nrisk factor may actually have used drugs but denied it. The majority of nevidence supports there being no risk for monogamous heterosexual couples. nSexual practices that involve higher levels of trauma to the anogenital mucosa, nsuch as anal npenetrative sex, or that occur when there is a concurrent sexually transmitted infection, including HIV or genital ulceration, do npresent a risk. The United States Department of Veterans Affairs recommends condom use to prevent hepatitis C ntransmission in those with multiple partners, but not those in monogamous nrelationships.
Body modification
Tattooing nis associated with two to threefold increased risk of hepatitis nC. This can be due to either improperly sterilized equipment or ncontamination of the dyes being used. Tattoos or piercings performed neither before the mid-1980s, “underground,” or nnonprofessionally are of particular concern, since sterile techniques in such nsettings may be lacking. The risk also appears to be greater for larger ntattoos. It is estimated that nearly half of prison inmates share unsterilized ntattooing equipment. It is rare for tattoos in a licensed facility to be ndirectly associated with HCV infection.
Shared personal items
Personal-care items such as razors, toothbrushes, and nmanicuring or pedicuring equipment can be contaminated with blood. Sharing such nitems can potentially lead to exposure to HCV. Appropriate caution should be ntaken regarding any medical condition that results in bleeding, such as cuts nand sores. HCV is not spread through casual contact, such as hugging, kissing, nor sharing eating or cooking utensils. Neither is it transmitted through food nor water.
Vertical transmission
Vertical transmission of hepatitis C nfrom an infected mother to her child occurs in less than 10% of pregnancies. nThere are no measures that alter this risk. It is not clear when during pregnancy ntransmission occurs, but it may occur both during gestation and at delivery. A nlong labor is associated with a greater risk of transmission. There is no nevidence that breast-feeding nspreads HCV; however, to be cautious, an infected mother is advised to avoid nbreastfeeding if her nipples are cracked and bleeding, or her viral loads are nhigh.
Epidemiology
It is estimated that 150–200 million people, or ~3% of the world’s npopulation, are living with chronic hepatitis C. About 3–4 milliopeople are infected per year, and more than 350,000 people die yearly from nhepatitis C-related diseases. During 2010 it is estimated that 16,000 people ndied from acute infections while 196,000 deaths occurred from liver cancer nsecondary to the infection. Rates have increased substantially in the 20th ncentury due to a combination of intravenous drug abuse and reused but poorly nsterilized medical equipment.
Rates are high (>3.5% npopulation infected) in Central and East Asia, North Africa and the Middle nEast, they are intermediate (1.5%-3.5%) in South and Southeast Asia, nsub-Saharan Africa, Andean, Central and Southern Latin America, Caribbean, nOceania, Australasia and Central, Eastern and Western Europe; and they are low n(<1.5%) in Asia Pacific, Tropical Latin America and North America.
Among those chronically ninfected, the risk of cirrhosis nafter 20 years varies between studies but has been estimated at ~10%-15% for nmen and ~1-5% for women. The reason for this difference is not known. Once ncirrhosis is established, the rate of developing hepatocellular carcinoma is ~1%-4% per year. Rates of new ninfections have decreased in the Western world since the 1990s due to improved nscreening of blood before transfusion.
In the United States, about n2% of people have hepatitis C, with the number of new ncases per year stabilized at 17,000 since 2007. The number of deaths from nhepatitis C has increased to 15,800 in 2008 and by 2007 had overtaken HIV/AIDS nas a cause of death in the USA. This mortality rate is expected to increase, as nthose infected by transfusion before HCV testing become apparent. In Europe the npercentage of people with chronic infections has been estimated to be betwee0.13 and 3.26%.
The total number of people nwith this infection is higher in some countries in Africa and Asia. Countries with particularly high rates nof infection include Egypt (22%), Pakistan (4.8%) and China (3.2%). It is nbelieved that the high prevalence in Egypt is linked to a now-discontinued nmass-treatment campaign for schistosomiasis, using nimproperly sterilized glass syringes.
History
In the mid-1970s, Harvey J. Alter, Chief nof the Infectious Disease Section in the Department of Transfusion Medicine at nthe National Institutes of Health, and his research team ndemonstrated how most post-transfusion hepatitis ncases were not due to hepatitis nA or B nviruses. Despite this discovery, international research efforts to identify the nvirus, initially called non-A, non-B hepatitis (NANBH), failed for the nnext decade. In 1987, Michael Houghton, Qui-Lim Choo, and nGeorge Kuo at ChiroCorporation, collaborating with Dr. D.W. Bradley at the Centers for Disease Control and Prevention, nused a novel molecular ncloning approach to identify the unknown organism and develop a ndiagnostic test. In 1988, Alter confirmed the virus by verifying its presence nin a panel of NANBH specimens. In April 1989, the discovery of HCV was npublished in two articles in the journal Science. The ndiscovery led to significant improvements in diagnosis and improved antiviral ntreatment. In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical nResearch for “pioneering work leading to the discovery of the virus that causes nhepatitis C and the development of screening methods that reduced the risk of nblood transfusion-associated hepatitis in the U.S. from 30% in 1970 to nvirtually zero in 2000.”
Chiron filed for several npatents on the virus and its diagnosis. A competing patent application by the nCDC was dropped in 1990 after Chiron paid $1.9 million to the CDC and n$337,500 to Bradley. In 1994, Bradley sued Chiron, seeking to invalidate the npatent, have himself included as a coinventor, and receive damages and royalty nincome. He dropped the suit in 1998 after losing before an appeals court.
Hepatitis D (VHD)
http://emedicine.medscape.com/article/178038-overview
Hepatitis D, also referred to as hepatitis D virus (HDV) and classified nas Hepatitis delta virus, is a disease ncaused by a small circular enveloped RNA virus. It is one nof five known hepatitis viruses: A, B, C, D, and E. HDV is considered nto be a subviral nsatellite because it can propagate only in the presence of the hepatitis B virus n(HBV). Transmission of HDV can occur either via simultaneous infection with HBV n(coinfection) or nsuperimposed on chronic hepatitis B or hepatitis B carrier state (superinfection).
Both superinfection and ncoinfection with HDV results in more severe complications compared to infectiowith HBV alone. These complications include a greater likelihood of nexperiencing liver failure in acute infections and a rapid progression to liver ncirrhosis, with aincreased chance of developing liver cancer ichronic infections. In combination with hepatitis B virus, hepatitis D has the nhighest mortality rate of all the hepatitis infections, at 20%.
VHD represents itself defective virus particle of size 30 – 35 nm, ncontains internal antigen (HDAg), made up of small circular RNA and surface ncovering, which is HBsAg VHB. It is considered that reproduction of virus is npossible only during presence of HBsAg in organism of patient, therefore nhepatitis D proceeds always as a coinfection or superinfection, joining to VHB.
Human’s norganism replies on internal VHD by production of antibodies of class IgM, nwhich used in diagnostics of the disease.
Hepatitis ndelta virus delta antigen
History
Hepatitis D nvirus was first reported in the mid-1977 as a nuclear antigen in patients ninfected with HBV who had severe liver disease This nuclear antigen was thethought to be a hepatitis B antigen and was called the delta antigen. nSubsequent experiments in chimpanzees showed that the hepatitis delta antige(HDAg) was a structural part of a pathogen that required HBV infection to nreplicate The entire genome was cloned and sequenced in 1986. It was nsubsequently placed in its own genus: Deltavirus.
Structure and genome
The HDV is a nsmall, spherical virus with a 36 nm diameter. It has an outer coat ncontaining three HBV envelope proteins (called large, medium, and small nhepatitis B surface antigens), and host lipids surrounding an inner nnucleocapsid. The nucleocapsid contains single-stranded, circular RNA of 1679 nnucleotides and about 200 molecules of hepatitis D antigen (HDAg) for each ngenome. The central region of HDAg has been shown to bind RNA. Several ninteractions are also mediated by a coiled-coil region at the N terminus of HDAg. The hepatitis D circular genome is unique to animal nviruses because of its high GC nucleotide content. The HDV genome exists as aenveloped, negative sense, single-stranded, closed circular RNA. Its nucleotide sequence nis 70% self-complementary, allowing the genome to nform a partially double-stranded, rod-like RNA structure. With a genome of napproximately 1700 nucleotides, HDV is the smallest „virus” known to infect nanimals. It has been proposed that HDV may have originated from a class of nplant pathogens called viroids, which are much smaller nthan viruses.
Life cycle
The receptor that HDV recognizes on human hepatocytes has not beeidentified; however it is thought to be the same as the HBV receptor because nboth viruses have the same outer coat. HDV recognizes its receptor via the nN-terminal domain of the large hepatitis B surface antigen, HBsAg. Mapping by nmutagenesis of this domain has shown that amino acid residues 9–15 make up the nreceptor binding site. After entering the hepatocyte, the virus is uncoated and nthe nucleocapsid translocated to the nucleus due to a signal in HDAg Since the nnucleocapsid does not contain an RNA polymerase to replicate the virus’ genome, nthe virus makes use of the cellular RNA npolymerases. Initially just RNA pol II, now RNA polymerases I and nIII have also been shown to be involved in HDV replication Normally RNA npolymerase II utilizes DNA as a template and produces mRNA. Consequently, if nHDV indeed utilizes RNA polymerase II during replication, it would be the only nknown animal pathogen capable of using a DNA-dependent polymerase as aRNA-dependent polymerase.
The RNA polymerases treat the nRNA genome as double stranded DNA due to the folded rod-like structure it is nin. Three forms of RNA are made; circular genomic RNA, circular complementary nantigenomic RNA, and a linear polyadenylated antigenomic RNA, which is the mRNA ncontaining the open reading frame for the HDAg. Synthesis of antigenomic RNA noccurs in the nucleolus, mediated by RNA Pol I, whereas synthesis of genomic nRNA takes place in the nucleoplasm, mediated by RNA Pol II. HDV RNA is nsynthesized first as linear RNA that contains many copies of the genome. The ngenomic and antigenomic RNA contain a sequence of 85 nucleotides, the Hepatitis delta virus ribozyme, that acts as a nribozyme, which nself-cleaves the linear RNA into monomers. These monomers are then ligated to nform circular RNA.
There are eight reported genotypes of HDV with nunexplained variations in their geographical distribution and pathogenicity.
Delta antigens
A significant ndifference between viroids and HDV is that, while viroids produce no proteins, nHDV is known to produce one protein, namely HDAg. It comes in two forms; a n27kDa large-HDAg, and a small-HDAg of 24kDa. The N-terminals of the two forms nare identical, they differ by 19 more amino acids in the C-terminal of the nlarge HDAg. Both isoforms are produced from the same reading frame which ncontains an UAG stop codon at codon 196, which normally produces only the nsmall-HDAg. However, editing by cellular enzyme adenosine deaminase-1 changes nthe stop codon to UCG, allowing the large-HDAg to be produced. Despite having n90% identical sequences, these two proteins play diverging roles during the ncourse of an infection. HDAg-S is produced in the early stages of an infectioand enters the nucleus and supports viral replication. HDAg-L, in contrast, is nproduced during the later stages of an infection, acts as an inhibitor of viral nreplication, and is required for assembly of viral particles. Thus RNA editing nby the cellular enzymes is critical to the virus’ life cycle because it nregulates the balance between viral replication and virion assembly.
Hepatitis E (VHE)
http://www.ystwt.com/wantai_english/HEV.html
Hepatitis E is a viral hepatitis n(liver inflammation) caused by infection nwith a virus called hepatitis E virus n(HEV). HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 nkilobase genome. HEV has a fecal-oral transmission route. It is one of five nknown hepatitis viruses: A, B, C, D, and E. Infectiowith this virus was first documented in 1955 during an outbreak in New Delhi, India. A preventative vaccine n(HEV 239) is approved for use in China.
The incidence of hepatitis E nis highest in juveniles and adults between the ages of 15 and 40. Though nchildren often contract this infection as well, they less frequently become nsymptomatic. Mortality rates are generally low, for hepatitis E is a “self-limiting” disease, in that it usually goes naway by itself and the patient recovers. However, during the duration of the infection (usually nseveral weeks), the disease severely impairs a person’s ability to work, care nfor family members, and obtain food. Hepatitis E occasionally develops into aacute, severe liver disease, and is nfatal in about 2% of all cases. Clinically, nit is comparable to hepatitis nA, but in pregnant women the disease is more often severe and is nassociated with a clinical syndrome called fulminant hepatic failure. Pregnant women, especially those ithe third trimester, suffer an elevated mortality rate from nthe disease of around 20%.
Virus of hepatitis E has been isolated from feces of patients with njaundice. Spherical particles similar to virus were able to discover due to the nmethod of immune electronic microscopy. Material for investigation was ncollected from volunteers, infected by material from patients with jaundice nwith assumed diagnosis of viral hepatitis E. It is supposed, that VHE may be ncaused by few strains of virus of different antigens.
At present ntime a test-system, giving the possibility of discovering antigens of virus ifecal matter has been elaborated. Serums of reconvalescenes nare used for that.
There is only one serotype of nthe virus and classification is based on the nucleotide sequences of the ngenome. Genotype 1 has been classified into five subtypes. The number of ngenotype 2 can be classified into two subtypes. Genotypes 3 and 4 have beeinto ten and seven subtypes respectively.
Differences have beeoted between the different ngenotypes. For genotype 1, the age at which incidence peaks is between 15 and n35 years and mortality is about 1%. Genotype 3 and 4—the most common iJapan—are more common in people older than 60 years and the mortality is nbetween 5 and 10%.
Distribution
Genotype 1 has been isolated nfrom tropical and several subtropical countries in Asia and Africa. Genotype 2 nhas been isolated from Mexico, Nigeria, and Chad. Genotype 3 has been isolated nalmost worldwide including Asia, Europe, Oceania, North and South America. nGenotype 4 appears to be limited exclusively to Asia.
Genotypes 1 and 2 are nrestricted to humans and often associated with large outbreaks and epidemics ideveloping countries with poor sanitation conditions. Genotypes 3 and 4 infect nhumans, pigs and other animal species and have been responsible for sporadic ncases of hepatitis E in both developing and industrialized countries.
In the United Kingdom the Department for Environment, Food nand Rural Affairs (DEFRA) said that the number of human hepatitis E ncases increased by 39% between 2011 and 2012.
Transmission
Hepatitis E is prevalent imost developing countries, and common in any country with a hot nclimate. It is widespread in Southeast Asia, northern and central Africa, nIndia, and Central America. It is spread mainly by the fecal-oral route due nto fecal contamination of water supplies or food; person-to-person transmission is uncommon.
The incubation period nfollowing exposure to the hepatitis E virus ranges from three to eight weeks, nwith a mean of 40 days. Outbreaks of epidemic hepatitis E most commonly occur nafter heavy rainfalls and monsoons nbecause of their disruption of water supplies. Major outbreaks have occurred iNew Delhi, India (30,000 cases in 1955–1956), Burma (20,000 cases in 1976–1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).
DEFRA said that there was nevidence that the increase in hepatitis E in the UK was due to food-borne zoonoses, citing a nstudy that found 10% of pork sausages on sale in the UK contained the virus. nSome research suggests that food must reach a temperature of 70°C for 20 nminutes to eliminate the risk of infection. An investigation by the Animal Health and Veterinary nLaboratories Agency found hepatitis E in 49% of pigs in Scotland.
Animal reservoir
Domestic animals have beereported as a reservoir for the hepatitis E virus, with some surveys showing ninfection rates exceeding 95% among domestic pigs. Replicative virus has beefound in the small nintestine, lymph nnodes, colon nand liver of nexperimentally infected pigs. Transmissioafter consumption of wild boar nmeat and uncooked deer meat has been reported as well. The rate of transmissioto humans by this route and the public health importance of this are, however, nstill unclear.
A number of other small mammals have been identified nas potential reservoirs: the lesser bandicoot rat (Bandicota bengalensis), the black rat (Rattus rattus brunneusculus) nand the Asian house shrew (Suncus murinus). A nnew virus designated rat hepatitis E virus has been isolated.
A rabbit hepatitis E virus has also been described.
An avian virus has been described that is associated nwith hepatitis-splenomegaly syndrome in chickens. This virus nis genetically and antigenically related to mammalian HEV, and probably nrepresents a new genus in the family.
Molecular biology
Although it was originally nclassified in the Caliciviridae nfamily, the virus has since been classified into the genus Hepevirus, and has nbeen reassigned into the Hepeviridae family. The virus itself is a small nnon-enveloped particle.
The genome is approximately n7200 bases in length, is a polyadenylated single-strand RNA molecule that ncontains three discontinuous and partially overlapping opereading frames (ORFs) along with 5′ and 3′ cis-acting elements, nwhich have important roles in HEV replication and transcription. ORF1 encode a methyltransferase, protease, helicase and replicase; ORF2 encode nthe capsid protein and ORF3 nencodes a protein of undefined function. A three-dimensional, atomic-resolutiostructure of the capsid protein in the context of a virus-like particle has nbeen described. An in vitro culture system is not yet available.
As of 2009 there are napproximately 1,600 sequences of both human and animal isolates of HEV navailable in open-access sequence databases.
Species of this genus infect humans, pigs, boars, ndeer, rats, rabbits and birds.
The hepatitis E virus causes naround 20 million infections a year. These result in around three million acute nillnesses and as of 2010 57,000 deaths annually. It is particularly dangerous nfor pregnant women, who can develop an acute form of the disease that is lethal nin 20 per cent of cases. The virus (HEV) is a major cause of illness and of ndeath in the developing world and disproportionate cause of deaths among npregnant women.
Recent outbreaks
In 2004, there were two major noutbreaks, both of them in sub-SaharaAfrica. There was an outbreak in Chad in which, as of September 27, there were n1,442 reported cases and 46 deaths. The second was in Sudan with, as of September 28, 6,861 cases nand 87 deaths. Increasingly, hepatitis E is being seen in developed nations, nwith reports of cases in the UK, US and Japan. The disease is thought to be a nzoonosis in that animals are thought to be the source. Both deer and swine have nbeen implicated.
In October 2007, an epidemic nof hepatitis E was suspected in Kitgum District of northern Uganda where no nprevious epidemics had been documented. This outbreak has progressed to become none of the largest hepatitis E outbreaks in the world. By June 2009, the nepidemic had caused illness in >10,196 persons and 160 deaths.
In 2011, a minor outbreak was nreported in Tangail, a neighborhood of Dhaka, Bangladesh.
In June 2012, an outbreak was nreported in city of Ichalkaranji, nMaharashtra, India. As of June 14, 2012, 3232 cases were reported and 18 died. nand 3 died in Shirol taluka of Kolhapur Maharashtra, India in June 2012. nOfficials in the Indian state of Maharashtra India suspect that contaminated nwater from the Panchganga river was responsible for the hepatitis E outbreak iIchalkaranji.
In July 2012, an outbreak was nreported in South Sudanese refugee camps in Maban County near the Sudan border. South Sudan‘s Ministry nof Health reported over 400 cases and 16 fatalities as of September 13, 2012. nProgressing further, as of February 2, 2013, 88 have died due to the outbreak. nThe “Medical charity Medecins Sans nFrontieres (MSF) said it had treated almost 4,000 patients.”
History
The most recent commoancestor of Hepatitis E evolved between 536 and 1344 years ago. It diverged ninto two clades—an anthropotropic and an enzootic form—which subsequently nevolved into genotypes 1 and 2 and genotypes 3 and 4 respectively. The ndivergence dates for the various genotypes are as follows: Genotypes 1/2 n367–656 years ago; Genotypes 3/4 417–679 years ago. For the most recent commoancestor of the various viruses themselves: Genotype 1 between 87 and 199 years nago; Genotype 3 between 265 and 342 years ago; and Genotype 4 between 131 and n266 years ago. The anthropotropic strains (genotype 1 and 2) have evolved more nrecently than the others suggesting that this virus was originally a zooenosis.
The use of an avian straiconfirmed the proposed topology of the genotypes 1–4 and suggested that the ngenus may have evolved 1.36 million years ago n(range 0.23 million years ago nto 2.6 million years ago). nThe use of a rat sequence also confirmed this topology and estimated date of ndivergence from the swine/human strains was 7.44×104 years ago n(range 2.1×104 to 1.4×105 years ago). Since nthis date is approximately coincident with the advent of agriculture it may be nthat this virus originally infected rats and subsequently spread to pigs and nthen to humans. Additional work is required to support or refute this possibility nas very few sequences have been isolated from species other than humans and nsuids.
Genotypes 1, 3 and 4 all nincreased their effective population sizes in the 20th century. The populatiosize of genotype 1 increased noticeably in the last 30–35 years. Genotypes 3 nand 4 population sizes began to increase in the late 19th century up to n1940–1945. Genotype 3 underwent a subsequent increase in population size until nthe 1960s. Since 1990 both genotypes’ population sizes have been reduced back to levels last seein the 19th century.
The overall mutation rate for the genome has beeestimated at ~1.4×10−3 substitutions/site/year.
Pathogenesis
Pathogenesis of viral hepatitis is still not studied completely due to nbig difficulties, caused by absence of accessible experimental model of the ndisease. At the base of existing notions about pathogenesis of acute nviral hepatitis lay clinical observations, life time investigations of nliver tissue and comparative study of viral hepatitis in animals.
Entrance of the agent of the disease into the organism of patient takes nplace perorally (VHA, VHE), by sexual way (VHB, VHC), parenteral by (VHB, VHC, nVHD and not excluded for VHA – VHE), vertically (not excluded for all nviral hepatitis).
The agent approaches regional lymphatic glands, where its massive nreproduction takes place the second phase of pathogenetic process. The agent ncauses damage of cells and their death. Organism replies on this negative ninfluence by immune reaction of reticular tissue of the lymphatic glands, nexecuting “barrier” function. This corresponds to period of incubation. On this nlevel infections process may stopped. In insufficiency of “barrier” functiothe phase of generalization of infection (primary virusemia) begins.
Virus ncontinues to enter from lymphatic glands into blood in a large quantities. nClinically this phase is manifested by signs of intoxication and beginning of nthe damage of liver. In this phase viruses of hepatitis are connected n with thrombocytes. Due to composition of their phospholipid membrane they nviolate, metabolism of arachidonic acid is intensified, that leads to increase nin their adhesive and aggregate activeness. Viruses of hepatitis also render naction on cells of endothelium of small vessels, cause destruction of the nstructure of their biomembrane. As a result of such influence, highly active nendoperoxides are formed from arachidonic acid (compulsory component of nphospholipids of membrane), rendering powerful influence on adhesion and naggregation of thrombocytes, erythrocytes. Such influence of viruses of nhepatitis on the cells of blood cells of endothelium of vessels already nin the phase of virusemia renders essential influence on coagulative and nanticoagulative system of the blood causes disseminated intravascular ncoagulopathy. The first stage of DIС-syndrome develops. Degree of these disorders depends on massivity of nvirusemia and determines the disease.
The phase of virusemia is confirmed by relevation HBsAg in the blood of nthe patients. Besides virusemia parenchymatous diffusion happens too. Viruses nof hepatitis penetrates into the liver cells, at first, into erythrocytes. nReproduction of virus is realized in hepatocytes. Virus also revealed ierythrocytes, thrombocytes, in the cells of pancreas, reticuloendothelial nsystem. The inculcation of virus into hepatocytes leads to disorder of nintracellular metabolic process, especially in membranes of hepatocytes. nThe lesion of membranes accelerates destruction of hepatocytes.
The mechanism of the damage of hepatocytes, other cells of the norgans and systems in studied insufficiently. Syndrome of cytolisis also plays nthe leading role in pathogenesis of viral hepatitis B. However, virus of nhepatitis B doesn’t possess the direct cytopathogenic action.
F.Dubleu, A. Bluger consider that immune reactions, connected nwith T-cells, have the leading meaning in the pathogenesis of syndrome of ncytolisis. The penetration of virus into hepatocytes and reproduction ihepatocytes leads to accumulation of viruses in surface membrane. Circulatioof antigens in the blood causes sensibilization of T-lymphocytes. The nactivation of T-lymphocytes leads to distinction and depression of the agent nand to differention of subpopulation of T-lymphocytes. Effect of T-killer ncauses cytolisis of hepatocytes. Autoimmune reactions intensify ncytolitic syndrome and necrosis of liver.
Pathogenesis of viral hepatitis B is explained from viral-immunogenetic nposition, because it is known that power of immune response is genetically ndeterminated. Immune reaction may be strong (in fulminate form of hepatitis), nflabby and adequate. Only adequate immune reaction promotes cyclic course and nfavorable outcomes of the disease.
The scientific achievements of the nlast years opened new points of view to pathogenesis and therapy of different nforms of viral hepatitis. The study of metabolic processes on the level of cell nallowed to opeew aggressive components having negative influence on its nstructure and functions.
The surplus activity of the processes of freeradical oxygenation renders ndestructive influence on cell’s membranes. As a result free radicals are naccumulated in the cells. The process oxygenation of lipids is intensified n(peroxide oxygenation lipids – POL). It is known that lipids are the basic nstructural component of the cells. Antioxydant system of the organism is ndefending mechanism, supporting free radical oxygenation of the physiological nlevel. Due to investigations of the last years it was shown that activation of nthe processes of peroxide oxygenation of lipids plays the essential role in the npathogenesis of viral hepatitis and leads to alteration of structure and nfunctions of membrane of hepatocytes, thrombocytes and other cells. It’s worth nto underline that simultaneously with activation of POL the considerable ndepression of antioxydantic activity of the blood serum is marked.
In case of nextremely high activity of POL exhaustion of AOS takes place, which leads to ndisorder of activity of cellular ferments, particullary of glucolysis, nglucohenolysis and to rupture of phoshorilation. As a result, cell loses nenergetic potential. It leads to destruction of cell. Along with this npermeability of membrane of hepatocyte and its internal structural components nare disturbed. Corrosion of hepatocyte takes place, its synthetic, ndisintoxicative and other function are lost. Disturbance of permeability of nlysosomal membranes causes exit proteolytic ferment into cytoplasm, which ncomplete the death of hepatocyte.
At nthe last years data about molecular mechanism of the damage of hepatocyte’s nmembranes were received. It is known that interferones cause depressioof reproduction of viruses.
Leukocytaric and fibroblastic interferones may be produced practically by nall cells. Immune gamma-interferon is produced by ngamma-interferon immunocompetentive cells during immune response.
Interferon may ninfluence to complex of defensive reaction (phagocytosis, inflammation, antigeexpression). Interferon is the most important factor of nonspecific resistance. nHowever, interferon has influence to differentiation and activation of neffectoric cells of immune system. The activation of monocytes (macrophages), nincreased generation of peroxide radicals, increased phagocytes activity are nobserved under influence of interferon. Thus, at the present time interferon is nconsidered not only as antiviral remedy, but also as important regulator of ninteraction between cells. Due to investigations of the last time it was nestablished that antiviral effect of interferon is not connected with direct ninteraction with viruses. Antiviral effect is connected with change of nmetabolic processes in the cells.
It is established that nthere is decreased produce of interferon in the patients with viral hepatitis nB, especially in patient with severe course of the disease. In fulminate course nof acute viral hepatitis B interferon is not revealed in the blood serum.
Clinical manifestations
Clinical picture of all viral hepatitis is very much similar and differs nin percent relation by severity of the course of the disease and its outcomes. nViral hepatitis A and E are characterized by cyclic benign course with complete nreconvalescence. In hepatitis B, C and D medium serious and serious course, nlingering and chronic forms of disease and lethal consequences are inrarely nobserved.
Depending upon the expressiveness of clinical manifestations of the ndisease and degree of functional disorders of liver, established by biochemical ntests, light, medium serious, serious and malignant (fulminate) forms of nviral hepatitis are differentiated. All atypical cases of the disease n(non-jaundice, obliterated, subclinical) are concerned to light forms, because nas clinical manifestations and functional changes are weakly expressed in such npatients.
During evaluation of severity of the disease expressiveness of nintoxication and jaundice is taken into attention along with enlargement of nsizes of liver and spleen, loss in weight, level of bilirubin in blood serum.
High intoxication, polyarthralgia, expressed dyspeptic symptomocomplex nare typical for fulminate and serious forms of viral hepatitis. Prolonged nintensive jaundice, hypotonia, bradycardia, changing into tachycardia, nslackness, subfebrile temperature, decrease in diuresis, testifies about nserious or even malignant course of viral hepatitis with indefinite nprognosis.
Laboratory tests are used for evaluation of severity of disease: tests of nconcentration of general bilirubin in blood serum of patients, the prothrombiindex.
Viral hepatitis have principally cyclic course. Incubation period is ndifferent. In hepatitis A it is in average 15-30 days, during viral nhepatitis B 30-180 days. The disease begins with signs of general nintoxication – so called pre-jaundice period. There are the next some nvariants of prejaundice period:
1) Dyspeptic variant. – The patients complain of nappetite absence, nausea, sometimes vomiting. Temperature is subfebrile. nDuration of period is 3-7 days.
2) Astenovegetative variant. – The patients ncomplain of weakness, headache, malaise, decrease of appetite. Body ntemperature is subfebrile or 37-38 ˚C;
3) Influenza-like variant. – The patients ncomplain of headache, weakness; muscular pain, decrease of appetite. Body ntemperature is 37.5-39 °C, and in separate cases 39-40 °C. Duration of 2nd and 3rd variant of prejudice period is of 5-7 days;
4) Polyarthralgic variant. – It is observed nprincipally during hepatitis B and C. Patients complain of pain in joints, nsometimes muscular pain is troubling, weakness, decrease of appetite. During nthis subfebrile temperature is in majority of the patients. Duration of this nperiod is composed of 7-14 days;
5) Mixed type – All above indicated signs nof intoxication are of different degree.
The next period of the disease is climax period. The state of nthe majority of the patient becomes better. The temperature is normalized, nurine becomes dark, colorness stool. Scleras are icteric, jaundice grows ngradually n(Fig.4). The nfurther course of the disease depends on degree of liver damage by the virus, nwhich determines the severity of the disease. During light course of viral nhepatitis jaundice grows in a period of 3-5 days. It is present on one level nduring one week. Disappearance of jaundice is observed on 15-16 day. Urine nbecomes more light at the end of the first-second week of the jaundice period, nit is of yellow or orange color.
During medium serious and serious course of the disease yellowish ncoloring of scleras and skin is more intensive, jaundice period is prolonged n(20-45 day). In majority of the patients the signs of cardiovascular system ndisorder are observed. There are hypotonia, bradycardia, muffed hearts sounds. nIn 80-90 % of the patients liver is enlarged, its surface is smooth, borders nare curved, moderately painful. In 30-40 % of patients spleen is palpated. nDuring serious course of viral hepatitis in some patients meteorism of abdomen, ncaused by disorders of digestion (signs of damage of pancreas, secretory glands nof stomach and disorders of biocenosis of gastro-intestinal tract) is observed. nIn some patients jaundice is very intensive and skin itch is observed (so ncalled cholestatic variant of the course of the disease.
Icteric sclera
Rash
Skin jaundice
Different nchanges are observed from central nervous system. Already during light course nof viral hepatitis changes adynamia, slackness, disorders of sleep may be npresent.
In serious ncases clear cerebral disorders caused by considerable dystrophic changes in the nliver, endogenic intoxication and increase of the activity of the processes nof POL are observed.
In the period nof reconvalescence reverse development of symptomatic of disease, normalizatioof biochemical indices is marked.
Hepatitis C infection causes acute symptoms in 15% of cases. Symptoms are ngenerally mild and vague, including a decreased appetite, fatigue, nausea, muscle or joint pains, and nweight loss and rarely does acute nliver failure result. Most cases of acute infection are not nassociated with jaundice. The ninfection resolves spontaneously in 10-50% of cases, which occurs more nfrequently in individuals who are young and female.
Chronic infection
About 80% of those exposed to the virus develop a chronic infection. This nis defined as the presence of detectable viral replication for at least six nmonths. Most experience minimal or no symptoms during the initial few decades nof the infection. Chronic hepatitis C can be associated with fatigue and mild ncognitive problems. Chronic infection after several years may cause cirrhosis or liver cancer. The nliver enzymes are normal in 7-53%. Late relapses after apparent cure have beereported, but these can be difficult to distinguish from reinfection.
Fatty changes to the liver noccur in about half of those infected and are usually present before cirrhosis ndevelops. Usually (80% of the time) this change affects less than a third of nthe liver. Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% nof hepatocellular carcinoma. About 10–30% of those infected develop cirrhosis nover 30 years. Cirrhosis is more common in those also infected with hepatitis B, schistosoma, or HIV, nin alcoholics and ithose of male gender. In those with hepatitis C, excess alcohol increases the nrisk of developing cirrhosis 100-fold. Those who develop cirrhosis have a n20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate nof 1–3% per year. Being infected with hepatits B in additional to hepatitis C nincreases this risk further.
Liver cirrhosis may lead to portal nhypertension, ascites n(accumulation of fluid in the abdomen), easy bruising or bleeding, nvarices (enlarged veins, especially in the stomach and esophagus), jaundice, and a nsyndrome of cognitive impairment known as hepatic encephalopathy. Ascites occurs at some stage in more nthan half of those who have a chronic infection.
Extrahepatic ncomplications
The most commoproblem due to hepatitis C but not involving the liver is mixed cryoglobulinemia n(usually the type II form) – an inflammation of small and nmedium-sized blood vessels. Hepatitis C is also associated with Sjögren’s syndrome (an autoimmune disorder); thrombocytopenia; lichen planus; porphyria cutanea tarda; necrolytic acral erythema; insulin resistance; diabetes mellitus; ndiabetic nephropathy; autoimmune thyroiditis and B-cell nlymphoproliferative disorders. Thrombocytopenia is estimated nto occur in 0.16% to 45.4% of people with chronic hepatitis C. 20-30% of people ninfected have rheumatoid nfactor – a type of antibody. Possible associations include Hyde’s prurigo nodularis and membranoproliferative glomerulonephritis. Cardiomyopathy with nassociated arrhythmias has also been reported. A variety of central nervous nsystem disorders have been reported. Chronic infection seems to be associated nwith an increased risk of pancreatic cancer.
Occult infection
Persons who have nbeen infected with hepatitis C may appear to clear the virus but remaiinfected. The virus is not detectable with conventional testing but can be nfound with ultra-sensitive tests. The original method of detection was by ndemonstrating the viral genome nwithin liver biopsies, but newer methods include an antibody test for the virus’ core protein and the detection of nthe viral genome after first concentrating the viral particles by ultracentrifugation. nA form of infection with persistently moderately elevated serum liver enzymes nbut without antibodies to hepatitis C has also been reported. This form is nknown as cryptogenic occult infection.
Several clinical pictures have been associated with this type of ninfection. It may be found in people with anti-hepatitis-C antibodies but with nnormal serum levels of liver enzymes; in antibody-negative people with ongoing nelevated liver enzymes of unknown cause; in healthy populations without nevidence of liver disease; and in groups at risk for HCV infection including nthose on haemodialysis or family members of people with occult HCV. The nclinical relevance of this form of infection is under investigation. The nconsequences of occult infection appear to be less severe than with chronic ninfection but can vary from minimal to hepatocellular carcinoma.
The rate of noccult infection in those apparently cured is controversial but appears to be nlow. 40% of those with hepatitis but with both negative hepatitis C serology nand the absence of detectable viral genome in the serum have hepatitis C virus nin the liver on biopsy. How commonly this occurs in children is unknown.
Complications
The most threatening outcome of viral hepatitis is acute or subacute nmassive nercosis of liver, during which picture of acute or subacute hepatic nencephalopathy is observed. An acute hepatic encephalopathy (AHE) is typical nfor acute hepatites.
The term “acute hepatic encephalopathy” denotes unconscious conditioof the patient with violation of reflex activity, convulsions, disorder nof life vital functions as a result of deep brake of action of ncerebral cortex with its spread on to subcortex and below laying parts of ncentral nervous system. This sharp brake action of nervous-psychic activity nis characterized by disorder of movements, sensibility, reflexes and by absence nof reactions on different irritators.
Hepatic coma is an endogenic coma, caused by endogenic intoxication as a nresult of loss of function and breakdown of liver.
There are the next stage of AHE – precoma I, precoma II and nproperly coma.
Precoma I is ncharacterized by non constant disorder of consciousness, unsuitability of mood, ndepression, lowered capability towards orientation, tremors, inversion of nsleep. Patients are irritated, sometimes – euphoric. They are troubled by nparoxysms of depression, doom, presentiment of death. Fainting, short time nunconsciousness, giddiness, hiccup, nausea, vomiting may be observed. nJaundice grows. Bradycardia is changed by tachycardia. Tendon reflexes nare raised. Such condition prolongs from few hours to 1 – 2 day with moving ninto second stage.
In the second nstage of precoma consciousness is more hampered, losses in memory is a ncharacteristic feature, alternated with attacks of tachymotor and sensory nexciment till delirium. During awakening orientation in time, space and actiois absent. Tendon reflexes are high. Jaundice raises sharply. nMuffed heart sounds, tachycardia, hypotonia are revealed.
Rhythm of nrespiration is disturbed. Liver begins to decrease in size. Hepatic ninsufficiency is inrarely accompanied with hemorrhagic syndrome due to ndevelopment DIC-syndrome. In 1/3 of patients nasal hemorrhages, ngastrointestinal hemorrhages, uterine bleeding and hemorrhages of other localizatioare observed. Diuresis decreases. Abdomen is inflated; peristaltic of intestine nis decreased. Such condition continues for 12 hours – 2 days.
During the nthird stage – properly coma – complete loss of consciousness and disappearance nof reflexes is marked. Pathological reflexes may be too. Rigidity of muscles of nextremities, hyperkineses, convulsive syndrome, and thereafter complete nareflexia are observed. Expressed tachycardia, hypotonia, disorder of rhythm of nrespiration are revealed. Diuresis decreased considerably till anuria. The ndeath of the patients is through 6-24 hours. The patients perish from massive nhemorrhages or in development of severe metabolic acidosis.
Diagnosis
Preliminary ndiagnosis of viral hepatitis is based on epidemiological anamnesis, finding of nthe development of the disease, clinical picture with account of peculiarities nof the ways of the transmission, duration of incubation period, presence of nprejaundice period, presence of typical subjective and objective signs with naccount of the patients age.
Diagnosis is confirmed by routine and specific laboratory tests. Iroutine blood test of the patients with viral hepatitis lymphocytosis is nobserved with moderately expressed course and in serious course of the disease n- anemia and leucopenia. ESR is slightly decreased. In urine urobilin and bile npigments are observed. During climax period, particularly during medium serious nand serious forms, there are no stercobilin in stool.
Increased content of general bilirubin, primarily on account of its ndirect fraction is observed in blood serum during all jaundice period. Ratio of ndirect and indirect fraction composes 3:1. In all patients already ipre-jaundice period of the disease, during all jaundice period and in the nperiod of early reconvalescence increased activity of ALT, AST is observed, ntestifying about the presence of cytolytic processes in liver.
Specific antigens (HBsAg) and nantibodies to antigens of all known at present time viruses of hepatitis are nrevealed in the blood of patients with help of these methods. Discovery of nantibodies of class of IgM testifies about acute disease. Discovery of nother classes of immunoglobulins antibodies testifies about lingering or nchronic course of viral hepatitis or about earlier infectious process or about ndisease in the past.
Although HAV is excreted ithe feces towards the end of the incubation period, nspecific diagnosis is made by the detection of HAV-specific IgM antibodies in the nblood. IgM antibody is only present in the blood following an acute nhepatitis A infection. It is detectable from one to two weeks after the initial ninfection and persists for up to 14 weeks. The presence of IgG antibody in the nblood means that the acute stage of the illness is past and the person is nimmune to further infection. IgG antibody to HAV is also found in the blood nfollowing vaccination and tests nfor immunity to the virus are based on the detection of this antibody.
During the acute stage of the infection, the liver nenzyme alanine ntransferase (ALT) is present in the blood at levels much higher thais normal. The enzyme comes from the liver cells that have been damaged by the nvirus.
Hepatitis A virus is present in the blood (viremia) and feces of ninfected people up to two weeks before clinical illness develops.
Serum IgG, IgM and ALT following hepatitis A virus infection
There are a number of ndiagnostic tests for hepatitis C, including HCV antibody enzyme immunoassay or ELISA, recombinant immunoblot assay, nand quantitative HCV RNA polymerase chain reaction (PCR). HCV RNA can be detected by PCR typically one to ntwo weeks after infection, while antibodies can take substantially longer to nform and thus be detected.
Serologic profile of nHepatitis C infection
Chronic hepatitis C is defined as infection with the hepatitis C virus npersisting for more than six months based on the presence of its RNA. Chronic ninfections are typically asymptomatic during the first few decades, and thus nare most commonly discovered following the investigation of elevated liver enzyme levels or during a routine screening of nhigh-risk individuals. Testing is not able to distinguish between acute and nchronic infections. Diagnosis in the infant is difficult as maternal antibodies nmay persist for up to 18 months.
Serology
Hepatitis C testing typically begins nwith blood testing to ndetect the presence of antibodies to the HCV, using an enzyme immunoassay. If nthis test is positive, a confirmatory test is then performed to verify the nimmunoassay and to determine the viral load. A nrecombinant immunoblot assay is used to verify the immunoassay and the viral nload is determined by a HCV RNA polymerase chain reaction. If there are no RNA nand the immunoblot is positive, it means that the person tested had a previous ninfection but cleared it either with treatment or spontaneously; if the nimmunoblot is negative, it means that the immunoassay was wrong. It takes about n6–8 weeks following infection before the immunoassay will test positive. A nnumber of tests are available as point of care testing which means that results are available nwithin 30 minutes.
Liver enzymes are variable during the initial part of nthe infection and on average begin to rise at seven weeks after infection. The nelevation of liver enzymes does not closely follow disease severity.
Biopsy
Liver biopsies are nused to determine the degree of liver damage present; however, there are risks nfrom the procedure. The typical changes seen are lymphocytes within the nparenchyma, lymphoid nfollicles in portal ntriad, and changes to the bile ducts. There are a number of blood ntests available that try to determine the degree of hepatic fibrosis and nalleviate the need for biopsy.
Screening
It is believed that only n5–50% of those infected in the United States and Canada are aware of their nstatus. Testing is recommended in those at high risk, which includes injectiodrug users, those who have received blood transfusions before 1992, those who nhave been in jail, those on long term hemodialysis, and nthose with tattoos. Screening is also recommended in those with elevated liver nenzymes, as this is frequently the only sign of chronic hepatitis. Routine nscreening is not currently recommended in the United States. In 2012, the U.S. Centers for Disease Control and Prevention n(CDC) added a recommendation for a single screening test for those born betwee1945 and 1965.
Differential diagnosis
Differential diagnosis of viral hepatitis is necessary to perform with ndiseases like leptospirosis, yersiniosis, mononucleosis, malaria, mechanic and nhemolytic jaundice, toxic hepatoses.
Leptospirosis nis characterized by acute beginning of the disease, often with chill, ncontinuation of fever during of climax of the disease and jaundice, pain imuscles, especially in calfs, hemorrhagic syndrome. In blood leucocytosis with nneuthrophillosis and shift in the formula to the left, accelerated ESR are nobserved. Activity of ALT and AST is moderately raised or normal relation of ndirect and indirect bilirubin 1:1. In blood serum concentration of urea and nresidual nitrogen increases. Stool is colored. In urine erythrocytes, nleukocytes, like wax cylinders are marked in large quantity. Diuresis decreased ntill anuria.
In generalized nforms of yersiniosis jaundice may be also observed, however it is accompanied nby fever, metastatic focuses in other organs and tissues, leucocytosis with nnuetrophilosis, accelerated ESR, aggravations and relapses. Diagnosis is nconfirmed by serological methods with specific yersiniotic antigen.
In malaria nthere are clear alternation of attacks fever with chills, replaced by heat and nsweat and periods of apyrexia. Often painful, increased in size spleen is nmarked. In blood hemolytic anemia, in fat drop blood and smear different forms nof malarial plasmodia are reveled. In blood serum indirect fraction of nbilirubin predominates.
In mechanic njaundice stones in gall bladder and bile passages, enlargement of head of npancreas and other signs are revealed with help of ultrasound investigation. Imajority of the patients moderate increase of activity of ALT, AST, nleukocytosis, accelerated ESR are marked. Hemolitic jaundice is characterized nby anemia, accelerated ESR, increase of indirect fraction of bilirubin. nStercobilin is always present in stool.
Differential ndiagnosis of VH with hepatoses is complicated and demands from doctor nthoughtful and painstaking work. During this essential significance possesses ncorrectly taken anamnesis.
Outcomes of the disease
Viral hepatitis most often ends with complete reconvalescence. In some npatients may be cholecystitis, cholangitis, pancreatitis, dyskinesia of bile nexcreting pathways after an acute hepatitis. In 5-10 % of patients lingering ncourse with periodical aggravations, caused by prolonged persistence of virus nis observed. In such cases chronic hepatitis develops. This variant of the ncourse of the disease is typical of viral hepatitis B and C chronic hepatitis nmay end up by liver cirrhosis.
Treatment
There is no specific treatment for hepatitis A. Sufferers are advised to nrest, avoid fatty foods and alcohol (these may be poorly tolerated for some nadditional months during the recovery phase and cause minor relapses), eat a nwell-balanced diet, and stay hydrated.
Treatment is used complex and depends on the clinical form and gravity of ndisease current. At mild current of a viral hepatitis in the acute period it is npossible to prescribe only semi-bed regime, diet № 5, polyvitamines and ndesensitizing preparations: calcium gluconate, Diazolin, Diprazin or Tavegil. nIn case of meteorism, feeling of gravity in epigastrium area after the meal, nunstable feces – Festal, Pancurmen, Allochol, Cholenzym are indicated.
At medioserious and serious current of the acute form of hepatitis a bed nregime is provided together with the specific treatment. Desintoxication ntherapy consists of plentiful drink; 5 % solution of glucose, saline solutions, nRinger’s solution, Trisault, Quartasault, 20 % solution of Sorbit (or. nSorbitoli), donor Albumin (given in vein), one of enterosorbents SKN of ndifferent brands, carbaphosfer, Carbosilan, Sillard P, Enterosgel, Polyphepan. nThe quantity of drunk liquid should be balanced with a daily urine. Polarizing nadmixture: 3.7 gm potassium of Sody chlorid and 12 UN of insulin on 1 liter of 5 % solution of glucose was recommended. There are indicated the preparations nimproving metabolism in hepatocytes: Ascorbinic acid, Thiamin chlorid, nPyridoxine hydrochloride, cocarboxylase, Potassy Orotat, Riboxin, Citochrom C, nLipamid, Calcy Pangamat. Last two preparations are indicated mainly at naccompanying hepatoses with fatty infiltration of liver (alcoholism, ndiabetes, thyrotoxicosis, an obesity etc.). For acidosis decreasing 2 n% solution of sodium of a hydrocarbonate 25-50 mL (P.R.) 3-4 ntimes per day or on 150-200 mL (I.V.) should be infused.
Among etiotropic agents moderate medical effect at acute virus hepatitis nhas human recombinative α-2-interferon – Reaferone, Intron A, nRealdironi or analogue Laferone in powder, in amp. 1 000 000 IUN: nfrom 1-st to 5-10-th day of the icteric period. Next days their efficiency nfalls. At acute hepatitis B Laferon is infused 1 000 000 IUN 2 times per nday during 5-6 days, then 1 000 000 IUN 1 time per day during 5 days. If nmedical effect is insufficient, there should be continued infusing 1 nmillion UN 2 times per week during 2 weeks. It is worthy to use Leicinferone as nthe basic component which is the admixture of natural α-interferons of ndonor leucocytes, the factor of necrosis of tumours and Interleicin-1. However nmany clinicians challenge expediency of indication of interferon at the nhepatitis of acute period. More physiologic is the stimulation of endogenic ninterferonogenesis with the help of such inductores, as Mefanam acid, nProdigiosan, Pyrogenal, Nifluril, Cycloferon.
At threat of hepatonecrosis – glucocorticoids 150-200 mg are nprescribed. The dose of prednisolon per day, must be reduced after the patient ngets out of extremely serious condition. The volume of infusion solutions is nenlarged up to 30-50 mL/kg per day. Ornithin (ornicetyl) promotes a linkage and nremoving out of organism nitrous bonds and improves a metabolism.
A lactulose reduces an adsorption of ammonia from intestine iblood, especially in combination with Neomycin. With the aim of oppression of nprocesses of an autolysis there should be used inhibitors of proteolytic nenzymes Contrical or Gordox each 8 hours (I.V.) intravenous dropping, at nimprovement of a condition synthetic inhibitors. At retention of liquid iorganism it is required to use Spironolacton (Veroshpiron), Kaliumsaving ndiuretics, or saluretics-Furosemid, Etacrinic acid. Psychomotor exaltation is nstopped by Sody hydroxybutyrate in combination with Sibazon (Seduxen), nHaloperidol. At increasing of hepatic failure there are used nantilymphocytic gamaglobulin during 1-5 days with the control of quantity of nlymphocytes in a pereferic blood, apparatus methods of clearing of patients nblood, hyperbaric oxygenation.
At ncholestatic form of a virus hepatitis the are effective preparations nwhich form complexes inside intestine with cholic acids which caot be soaked nup, cholestiramin and Bilignin. Fenobarbital is used which is the inductor of nsynthesis of Glucouroniltransferas. This enzym is necessary for conjugation of nbilirubin with glucuronic acid, and stimulating its egestion with bile. Fenobarbital nis indicated with combination of Cyanocobalamin. Simultaneously for nintensifying secretion of bile Nospan and Cholenzym are indicated. After the ntermination of an acholia duodenal tubages 5-10 % solution of magnesy nsulfat (1/4-1/2 glasses), Sorbit or Xilit (20 gr on 100 mL of hot water) 1 hour nbefore breakfast are applied.
Bioflavonoids – Convaflavin, Carsili, Legalone, Silibor, Quercetin are nindicated in case of the alonged reconvalescence. At hyperaminotransferasaemia n– Aevit or Tocopherol acetas, Thymalin, T-activin, Dipiridamol (Curantyl), nIsoprinosin (has also antiviral property) – give positive effects. There are nused also Saparal, Methyluracil (or. Methacil), Natry nucleinic, Thymalin in a ncombination with Dipiridamol, Hofitol.
Cholagogue nagents – broths of flowers of immortele, hips, thyme, mints peppery at the rate nof 1 dining spoon of a herb or a mixture to 1 glass of water are indicated for nconvalescents Fenobarbital with Cyanocobalamin are applied during 10 days icase of hyperbilirubinemia with prevalence of untied fraction of pigment; npreparations of choice can be Cordiamin or Sibazone (Seduxen) which also nstimulate glucoruniltransferase of hepatocytes. At hyperbilirubinemia nmainly at the expence of connected fraction stimulate a bile secretion using noxygen cocktails with cholagogue herbs and honey. Vitohepat or Cobamamid nstimulate neogenesis and hemopoes, accelerate regenerative processes in liver, ncourse of treatment lasts 15-20 days. At astenia and hypoproteinemia, and also nfor elimination of catabolitic influences of glucocorticoids which were used at nthe acute period, anabolic hormones: such as methandrostenolon (Nerobol), nPhenobolin (Nerobolil) or Retabolil are indicated. For elimination of the nasthenic phenomena, there are used Novopasit, tinctura of Valeriana root n(20 gm: 200 mL), herbs of neetle, Thyme, Bromidums, and in rather serious cases n- Chlozepid (or. Eleny), Sibazon (or. Seduxen), Relany, Barbiturates.
At the ndyspeptic phenomena caused by oppression of secretory function of digestioorgans, also Allochol, Liobily, Cholenzym, Festal, Panzynorm forte, Pancurmen, nPancreatin, Pancitratit, Vobensym are widely used.
At nposthepatitic hepatomegalias without signs of cytolisis it is not reasonable to nindicate Lydase – promoting a resorption of a fibrous tissue, 10 injections nevery 2-nd day. It can be infused only after exceptioof inflammatory process in hepatobiliar ways (will carry out control duodenal nintubation).
Chemotherapeutic npreparations are indicated in case of the bacterial cholecystitis. At mild ncurrent of disease it is possible to use only a fortnight course of Nicodin, nat appreciable changes antibiotics or Nitrofurans preparations are indicated.
It is npossible to make antibioticosensetivity of microorganisms allocated from bile. nFor definition there are used mediums, which content bile of the patient as nit influences on essentially activity of antibiotics. Use Ampicillin, nCarbenicilin Dinatry salt, Erythromicin, Cefazolin, Furazolidone, Furagin, at nCandida infection sody salt of Levorin. Chemiopreparations indicate in average ntherapeutic doses during 7 – 8 days.
Specific therapy of chronic virus hepatitises is carried out by npreparations of α-interferon (Intron A, Roferon, Realdiron, Reaferon, nLaferon). They are effective in case of low replicative activity of the virus ndetermined in blood virus DNA (HBeAg) at a hepatitis B and virus RNA at nhepatitis C. The additional indication is high activity of serum nAlanineaminotransferase. One of the specified preparations inject (I.M.) or nsubcuteneous 3 – 5 million IUN per day 3 times per week during 6 months. Treatment nshould be stopped, if positive results were not observed after 3 months. The npositive effect is observed at 40-50 % of patients with hepatit B and at 20-30 n% of patients with hepatit C. At chronic hepatit D less than 10 % of patients nare released from viruses even if treatment lasts 1 year. In some cases the nsuccess of immunotherapy of virus hepatitises may be increased if preliminary nindicate short course of treatment about 6 weeks of glucocorticoids. Combined nusage of interferon and Thymalin, Essentiale, Lamivudin, Chenodesoxycholyc nacids has been proved.
The nside-effects of α-interferon are noticed at half patients right after ninjection, among them are headache, fever, myalgia, arthralgia, general ndelicacy. They can be prevented by means of analgetics. Among the remote nside-effects are: nausea, diarrhea, depression, irritability, leuco- and nthrombocytopenia. Decreasing of a dose of preparation allows to weak nthese disorders. There are serious complications (sepsis, psychosis, autoimmune ndiseases), that demand an immediate cancellation of interferonotherapy.
At chronic hepatitis B in a phase of replication there are applied na peroral preparation Lamivudin (Zeffix). It provides the same level of nseroconversion, as standard course of treatment by interferon.
At nchronic hepatitis with low replicative activity of a virus preference is giveto pathogenetic agents improving metabolic and reparative processes in nliver, such as: Silibor, Carsil, Liv-52, Hepatofalk, Planta, Hepabenne, Antral, nTocopherol Acetat etc.
Prophylaxis
http://medicscientist.com/hepatitis-prophylaxis-and-hepatitis-treatment-and-management
If the patient is hospitalized, he should nbe placed in a private room with separate toilet facilities. The major reasofor such isolation is to prevent the spread of type A hepatitis. Even with lax nprecautions, such spread is very rare; most patients with type A hepatitis are nno longer excreting virus once they have become symptomatic. Nevertheless, there nare exceptions, and isolation is prudent. Secretions and blood products should nbe handled with care gowns, masks, and gloves are not necessary, but a nprominent sign reading “needle and blood precautions” is appropriate. Labeling nof blood specimens from a patient with hepatitis, is a common practice. It nshould be stressed, however, that all blood from any patient should be handled nas if potentially infectious.
If the patient with nviral hepatitis is at home, the patient should be advised nabout care in personal hygiene – careful hand washing. Attention also should nbe paid to blood and blood products and the handling of cuts and lacerations.
Recommendations regarding the prevention of acute nhepatitis are governed by the type of viral hepatitis that is being considered. nIn the case of acute type A hepatitis, all family members, and close personal ncontacts should receive immune serum globulin (ISG) at a dosage of 2-5 mL in as nsoon as possible after exposure. Office, factory, and school contacts do not need nto be treated. Immune serum globulin can be given for up to 4 weeks after nexposure, but it probably is only effective if given within 7-14 days.
Hepatitis A can be prevented nby vaccination, ngood hygiene and sanitation.
There are two types of nvaccines: one containing inactivated hepatitis A virus, and another containing na live but attenuated virus. Both provide active immunity against a future ninfection. The vaccine protects against HAV in more than 95% of cases for nlonger than 25 years. In the US the vaccine was first phased in 1996 for nchildren in high-risk areas, and in 1999 it was spread to areas with elevating nlevels of infection.
The vaccine is given by injection. An initial dose nprovides protection starting two to four weeks after vaccination; the second nbooster dose, given six to twelve months later, provides protection for over ntwenty years.
Vaccination programmes
The vaccine was introduced in 1992 and was initially nrecommended for persons at high risk. Since then Bahrain and Israel have nembarked on eradication programmes. Australia, China, Belarus, Italy, Spain and nthe United States have started similar programmes. The incidence of hepatitis A nwhere widespread vaccination has been practised has decreased dramatically. IChina and the United States the incidence of hepatitis A has decreased by 90% nsince 1990.[24][25]
In the case of acute type В hepatitis, nprophylaxis only needs to be provided for “regular” sexual contacts. The best nform of protection is argued Hepatitis В immune globulin (HBIG) at a dosage of n5 mL in as soon as possible and again 1 month later has been the conventional nrecommendation in this situation. However, the efficacy of HBIG in preventing nthe sexual spread of acute type В hepatitis has not been well proved. Iaddition, there is now evidence that postexposure immunization with HBV nvaccine, can attentuate or prevent acute type В hepatitis. Vaccine should be ngiven as soon as possible and then 1 month and 6 months later.
A hepatitis C vaccine, na vaccine capable of nprotecting against hepatitis nC, is not available. Although vaccines exist for hepatitis A and hepatitis B, ndevelopment of a hepatitis C vaccine has presented challenges. No vaccine is ncurrently available, but several vaccines are currently under development.
Over the last decade numerous nHCV vaccine approaches have been assessed in mice and primates. Only a small nfraction of animal HCV vaccine studies have progressed to human trials. The nmajority of these trials have evaluated potential therapeutic vaccines iHCV-infected patients. A smaller number have assessed vaccines in healthy nvolunteers; either with the aim of developing a prophylactic HCV vaccine or as na bridge to evaluating vaccine in HCV-infected patients.
Most vaccines work through ninducing an antibody nresponse that targets the outer surfaces of viruses. However the nHepatitis C virus is highly variable among strains and fast mutated, making aeffective vaccine is very difficult. The detailed structure of E2 envelope nglycoprotein, believed to be the key protein the virus uses to invade liver ncells, is elucidated by scientists at The Scripps Research Institute (TSRI) iNovember 2013. Due to the relatively conserved binding region of E2 to the CD81 receptor on the liver cells, this ndiscovery is expected to pave the way to design HCV vaccine which will nstimulate antibody response with neutralizing effects on broad range of virus nstrains. Another strategy which is different from conventional vaccine is to ninduce the T cell arm of the immune response using viral vectors, adenoviral vectors nthat contain large parts of the hepatitis C virus genome itself, to induce a T ncell immune response against hepatitis C.
Most of the work to develop a nT cell vaccine has been done against a particular genotype. There are nsix different genotypes which reflect differences in the structure of the nvirus. The first approved vaccine will likely only target genotypes 1a and 1b, nwhich account for over 60% of chronic HCV infections worldwide. Likely, nvaccines following the first approved vaccine will address other genotypes by nprevalence.
New HCV vaccine approaches, nincluding peptide, recombinant nprotein, DNA and vector-based vaccines, have recently reached nPhase I/II human clinical trials. Some of these technologies have generated nrobust antiviral immunity in healthy volunteers and infected patients. Novel nfuture vaccine approaches include virus-like particle (VLP)-based vaccines that nhave been successfully employed for viral infections such as hepatitis B. nAdditional strategies include molecules that induce innate immune responses, nwith secondary effects on adaptive responses (such as TLR-9 ligands) that are neither encoded within a vaccine construct or used as a vaccine adjuvant. The nchallenge now is to move forward into larger at-risk or infected populations to ntruly test efficacy.
Specific vaccines
One effort has involved use nof the hepatitis B core antigen. In a 2006 study, 60 patients nreceived four different doses of an experimental hepatitis C vaccine. All the npatients produced antibodies nthat the researchers believe could protect them from the virus. Nevertheless, nas of 2008 vaccines are still being tested. Some efforts have entered Phase nI/II human clinical trials.
SynCon will test a new HCV vaccine in humans in 2013. SyCon’s HCV vaccine can generate robust nT-cell responses not only in the blood, but also in the liver—an organ known to nsuppress T-cell activity.
Inovio is developing a synthetic multi-antigen DNA vaccine covering nhepatitis C virus (HCV) genotypes n1a and 1b and targeting the antigens NS3/4A, nwhich includes HCV nonstructural proteins 3 (NS3) and 4A (NS4A), nas well as NS4B and NS5A proteins. Inovio has the intent to initiate a phase nI/IIa clinical study in the fourth quarter of 2013. Following immunization, nrhesus macaques mounted strong nHCV-specific T cell immune responses strikingly similar to those reported ipatients who have cleared the virus on their own. The responses included strong nNS3-specific interferon-γ n(IFN-γ) induction, robust CD4 nand CD8 T cell proliferation, nand induction of polyfunctional T cells.
Improving sanitation is the most nimportant measure in prevention of hepatitis E; this consists of proper ntreatment and disposal of human waste, higher standards for public water nsupplies, improved personal hygiene procedures and sanitary food preparation. nThus, prevention strategies of this disease are similar to those of many others nthat plague developing nations, and they require large-scale international nfinancing of water supply and water treatment projects.
Vaccines
A vaccine based on recombinant viral proteins was ndeveloped in the 1990s and tested in a high-risk population (military personnel nof Nepal) in 2001. The vaccine appeared to be effective and safe, but ndevelopment stopped for economical reasons, since hepatitis E is rare ideveloped countries. There is no licensed hepatitis E vaccine for use in the nUS.
Although other HEV vaccine trials, including trials nconducted in populations in southern Asia, have shown candidate vaccines to be neffective and well-tolerated, these vaccines have not yet been produced or made navailable to susceptible populations. The exception is China. After more than a nyear of scrutiny and inspection by China’s State Food and Drug Administratio(SFDA), a hepatitis E vaccine developed by Chinese scientists was available at nthe end of 2012. This vaccine—called HEV 239 and sold as Hecolin by its ndeveloper Xiamen Innovax Biotech—was approved for prevention of hepatitis E i2012 by the Chinese Ministry of Science and Technology, following a phase 3 ntrial on two groups of 50,000 people each from Jiangsu Province where none of nthe vaccinated became infected during a 12-month period, compared to 15 in the ngroup given placebo treatment. The first vaccine batches came out of Innovax’ factory in late October 2012, and nwill be sold to Chinese distributors.
Prognosis
The prognosis of viral hepatitis nvaries, depending on the causative virus.
HAV infection usually is nmild and self-limited. Overall mortality is approximately 0.01%; childreyounger than 5 years and adults older than 50 years have the highest ncase-fatality rates. Infection confers lifelong immunity against the virus. nOlder patients are at greater risk for severe disease. Whereas icteric disease noccurs in fewer than 10% of children younger than 6 years, it occurs in 40-50% nof older children and in 70-80% of adults with HAV. Three rare complications nare relapsing hepatitis, cholestatic hepatitis, and FHF.
The risk of chronic HBV ninfection in infected older children and adults approaches 5-10%. Patients with nsuch infection are at risk for cirrhosis and HCC. FHF develops in 0.5-1% of npatients infected with HBV; the case-fatality rate in these patients is 80%. nChronic HBV infection is responsible for approximately 5000 deaths per year nfrom chronic liver disease in the United States. Chronic infection develops i50-60% of patients with hepatitis C. Chronically infected patients are at risk nfor chronic active hepatitis, cirrhosis, and HCC. In the United States, chronic HCV infection is the leading indication for liver transplantation, and an estimated n8,000-10,000 chronic liver disease deaths occur as a result of HCV infectioeach year.
Patients with chronic HBV ninfection who are coinfected with HDV also tend to develop chronic HDV ninfection. Chronic coinfection with HBV and HDV often leads to rapidly nprogressive subacute or chronic hepatitis, with as many as 70-80% of these npatients eventually developing cirrhosis.
HEV infection usually is nmild and self-limited. The case-fatality rate reaches 15-20% in pregnant women. nHEV infection does not nresult in chronic disease.
Patient neducation
Refer patients with ninfectious hepatitis to their primary care providers for further counseling nspecific to their disease; the specific etiologic virus is unlikely to be knowat the time of discharge from the emergency department.
Counsel patients regarding nthe importance of follow-up care to monitor for evidence of disease progressioor development of complications. Remind them to exercise meticulous personal nhygiene, including thorough hand washing. Instruct them not to share any narticles with potential for contamination with blood, semen, or saliva, nincluding needles, toothbrushes, or razors.
Inform food handlers nsuspected of having HAV that they should not return to work until their primary ncare physician can confirm that they are no longer shedding virus. Instruct npatients to refrain from using any hepatotoxins, including ethanol and nacetaminophen.
