VIRAL HEPATITIS WITH PARENTERAL MECHANISM OF TRANSMISSION. CLINIC, DIAGNOSIS, TREATMENT. IMMUNOPROPHYLAXIS OF VIRAL HEPATITIS A AND B. FEATURES OF INFECTION IN DENTAL PRACTICE. PLANNED AND EMERGENCY PREVENTION OF INFECTIOUS DISEASES. INDIVIDUAL PREVENTION.
HIV INFECTION AND HIV-ASSOCIATED INFECTIONS AND INFESTATIONS, ACCOMPANIED BY LESIONS OF ORAL MUCOSA.
General description of viral hepatitis. Clinical description of viral hepatitis with fecal-oral mechanism of transmission. Acute and chronic viral hepatitis with the parenteral way of transmission.
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The problem of the viral hepatitis remains most actual, as these diseases according to spread step down only to acute respiratory and acute intestinal infections. Viral hepatitis is most frequent reason of chronic hepatitis and liver cirrhosis. In some patients viral hepatitis may have lethal outcomes.
The problem of the viral hepatitis is present under fixed attention of many scientists of the whole world. At present time definite successes in study of etiology, epidemiology, clinic, diagnostics of this polyetiological viral disease have been possessed.
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Etiology
At present time further viruses, causing viral hepatitis are known: virus of hepatitis A (VHA); virus of hepatitis B (VHB); virus of hepatitis E (VHE); virus of hepatitis D (VHD); associated with VHB, virus of hepatitis C (VHC). Search of new viruses, causing viral hepatitis continues. In literature one may come across different names of disease, caused by these viruses: infection hepatitis, epidemic hepatitis, serum hepatitis, syringe hepatitis. Uniting all these terminis – Botkins disease. Indicated diseases caused by different viruses, possess many in general, however highly essential clinical, epidemiological, biochemical and immunological peculiarities that have been revealed. These peculiarities demand conduction of differential diagnosis between them. As a result of the above said, group of experts of WHO recommend to differentiate further variants of viral hepatitis: viral hepatitis A (VHA); viral hepatitis B (VHB); viral hepatitis E (VHE); viral hepatitis C (VHC); viral hepatitis D (VHD).
Hepatitis A (VHA)
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Agent was first discovered in 1973 by Feinstone. This is RNA-containing virus. Complete viral bodies as well as empty parts (capsules) with size of 27-30 nm can be noticed under electronic microscope. On their surfaces capsomeres are seen. Nucleopeptide of VHA(Fig.1) does not possess surface projections and covering. Core structure is not revealed in the virion.
Virus contains 4 peptides (VP1-4), participating in reactions of immune precipitation. It is assumed that VP1 and VP3 are located pertly on the surface and VP2 and VP4 are present inside the virion. However, up till date, there is not authentic informations about their meaning in relation to antiqenicity and immunogenicity.
Fig.1. Electronic microscopy (negative contrast) hepatitis virus A
VHA is stable during pH 3,0-9,0, sensitive to formaldehyde, may remain preserved for a period of few months or even years during temperature + 4 °C, for weeks – during room temperature. Complete inactivation of virus takes place during 85 °C in a period of 5 minutes. VHA is resistant to chlorine, in comparison with other viruses of this group and may enter through barriers of water cleaning stations. Complete inactivation of virus steps on during concentration of chlorine 2,0 – 2,5 mg/l with exposition for a period of 15 minutes, of lime chloride – 10 mg/l through 15 minutes.
Virus of hepatitis A may reproduce iumber of human and monkey cellular cultures, from where viral antigen is obtained. It is necessary to remark, that successful adaptation of VHA towards culture of cells is very much necessary for study of biological properties, for obtaining of source of reagents for diagnostics (antigen, antiserum), as well as for construction of vaccines, (live, killed).
Hepatitis B (VHB)
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VHB iatural condition is revealed in sick people and carriers, in forest marmots, in carth squirrels, in Peiking ducks. This DHA-containing virus (Fig.2) is pathogenic for human and few types of primates – chimpanzee, gorillas. VHB causes acute and persistent infection, primarily damages liver.
Virus consists of nucleus and covering. Further antigenic structure of VHB is differentiated: HBsAg – surface, HBcAg – internal (care), HBeAg – reflects infectiouness of virus.
Towards these antigens in organism of patients antibodies are produced: anti-HBs; anti-HBc; anti-HBe.
Presence of HBsAg in human organism testifies the presence of acute and latent proceeding infection. It is assumed, that prolonged conservation HbsAg in serum of the blood in sick man may testify about transfer of the process into chronic form. HBsAg is revealed in majority of patients in incubation stage. HBcAg is practically not determined in blood and fixed in directly by DNA-polymerize reactions, falling positive in acute period of disease, as well as after many months and years in carriers. Soon after discovery of HBsAg in blood of patients anti-HBc appear. Most often they are observed in carriers of infection. In early stages of disease HBeAg is revealed, which is then changed by anti-HBe.
Very important diagnostic information may be obtained by using methods of determination of DNA HB. For this purpose molecular hybridization of nucleic acids and polymerize chain reaction (PCR) is used. Genospecific viral DNA is observed in serum of blood, in bioptates of liver, in lymphocytes of peripheral blood. Mentioned method enables to discover very small quantities of viral DNA in investigated samples, which moderately increases reliability of diagnosis.
Fig.2. Electronic microscopy (negative contrast) hepatitis virus B
Hepatitis C (VHC)
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Virion of virus of hepatitis C consists of nucleus and lipid external membrane. Genome is represented by single chain RNA. VHC is heavily resistant in external medium, particularly in biological fluids such as preparations of blood, sperm and others. It is sensitive to chloroform, to other desinfective solutions and high temperatures (100 °C and more).
Antigenic structure of VHC is less studied. It is established, that to the antibodies are produced (class Ig M and G) to virus in the organism of the patient. Their discovery in blood serum of patient testifies presence of acute or chronic disease. Antibodies may stick to definite level during 6-9 months, and thereafter their titers in serum decrease upto complete disappearance.
Hepatitis D (VHD)
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VHD represents itself defective virus particle of size 30 – 35 nm, contains internal antigen (HDAg), made up of small circular RNA and surface covering, which is HBsAg VHB. It is considered that reproduction of virus is possible only during presence of HBsAg in organism of patient, therefore hepatitis D proceeds always as a coinfection or superinfection, joining to VHB.
Human’s organism replies on internal VHD by production of antibodies of class IgM, which used in diagnostics of the disease.
Hepatitis E (VHE)
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Virus of hepatitis E has been isolated from feces of patients with jaundice. Spherical particles similar to virus were able to discover due to the method of immune electronic microscopy. Material for investigation was collected from volunteers, infected by material from patients with jaundice with assumed diagnosis of viral hepatitis E. It is supposed, that VHE may be caused by few strains of virus of different antigens.
At present time a test-system, giving the possibility of discovering antigens of virus in fecal matter has been elaborated. Serums of reconvalescenes are used for that.
Epidemiology
Viral hepatitis A – antroponosis. The source of disease is sick person in prejaundice period and in 15-20 days of climax period of the disease and virus carrier. Primary localization of virus is gastrointestinal tract. Mechanism of transmission is fecal-oral. Virus is excreted from the organism of sick person with fecal matter. Specific final factors of transmission of hepatic A virus are water and blood. Character of infection of water depends upon conditions of water supply and its relation with fecal contamination. Intermediate factors of transmission are flies, transferring virus together with fecal matter on products of nutrition, dishes.
Susceptibility to the disease is high. Mainly children and adults up to 30 year fall sick.
The source of hepatitis B virus iature is sick person with acute or chronic form, healthy carrier. Natural path of transfer is sexual. Infection may be transferred even during kisses through traumatized mucous, through milk of mother, through placenta from sick mather to fetus (vertical path of transmission). Parenteral path of the transmission has blood transfusion and its preparations, meaning to injections, manipulation, operative intervention.
Susceptibility to the disease is high. Most often drug addicts, homosexuals, prostitutes, medical personnеl (surgeons, obstetrician – gynecologists, workers of hemodialysis departments, manipulative nurses, doctors-infectionists) often fall sick with hepatitis B.
Epidemiology of viral hepatitis D has been studied insufficiently. It is assumed, that source of infection is sick person, basic path of transmission is parenteral.
Persons suffering from VHB or HBsAg – carriers are more susceptible.
Epidemiology of viral hepatitis E is identical to epidemiological laws of VHA, and hepatitis C – to hepatitis B.
Pathogenesis
Pathogenesis of viral hepatitis is still not studied completely due to big difficulties, caused by absence of accessible experimental model of the disease. At the base of existing notions about pathogenesis of acute viral hepatitis lay clinical observations, life time investigations of liver tissue and comparative study of viral hepatitis in animals.
Entrance of the agent of the disease into the organism of patient takes place perorally (VHA, VHE), by sexual way (VHB, VHC), parenteral by (VHB, VHC, VHD and not excluded for VHA – VHE), vertically (not excluded for all viral hepatitis).
The agent approaches regional lymphatic glands, where its massive reproduction takes place the second phase of pathogenetic process. The agent causes damage of cells and their death. Organism replies on this negative influence by immune reaction of reticular tissue of the lymphatic glands, executing “barrier” function. This corresponds to period of incubation. On this level infections process may stopped. In insufficiency of “barrier” function the phase of generalization of infection (primary virusemia) begins.
Virus continues to enter from lymphatic glands into blood in a large quantities. Clinically this phase is manifested by signs of intoxication and beginning of the damage of liver. In this phase viruses of hepatitis are connected with thrombocytes. Due to composition of their phospholipid membrane they violate, metabolism of arachidonic acid is intensified, that leads to increase in their adhesive and aggregate activeness. Viruses of hepatitis also render action on cells of endothelium of small vessels, cause destruction of the structure of their biomembrane. As a result of such influence, highly active endoperoxides are formed from arachidonic acid (compulsory component of phospholipids of membrane), rendering powerful influence on adhesion and aggregation of thrombocytes, erythrocytes. Such influence of viruses of hepatitis on the cells of blood cells of endothelium of vessels already in the phase of virusemia renders essential influence on coagulative and anticoagulative system of the blood causes disseminated intravascular coagulopathy. The first stage of DIС-syndrome develops. Degree of these disorders depends on massivity of virusemia and determines the disease.
The phase of virusemia is confirmed by relevation HBsAg in the blood of the patients. Besides virusemia parenchymatous diffusion happens too. Viruses of hepatitis penetrates into the liver cells, at first, into erythrocytes. Reproduction of virus is realized in hepatocytes. Virus also revealed in erythrocytes, thrombocytes, in the cells of pancreas, reticuloendothelial system. The inculcation of virus into hepatocytes leads to disorder of intracellular metabolic process, especially in membranes of hepatocytes. The lesion of membranes accelerates destruction of hepatocytes.
The mechanism of the damage of hepatocytes, other cells of the organs and systems in studied insufficiently. Syndrome of cytolisis also plays the leading role in pathogenesis of viral hepatitis B. However, virus of hepatitis B doesn’t possess the direct cytopathogenic action.
F.Dubleu, A. Bluger consider that immune reactions, connected with T-cells, have the leading meaning in the pathogenesis of syndrome of cytolisis. The penetration of virus into hepatocytes and reproduction in hepatocytes leads to accumulation of viruses in surface membrane. Circulation of antigens in the blood causes sensibilization of T-lymphocytes. The activation of T-lymphocytes leads to distinction and depression of the agent and to differention of subpopulation of T-lymphocytes. Effect of T-killer causes cytolisis of hepatocytes. Autoimmune reactions intensify cytolitic syndrome and necrosis of liver.
Pathogenesis of viral hepatitis B is explained from viral-immunogenetic position, because it is known that power of immune response is genetically determinated. Immune reaction may be strong (in fulminate form of hepatitis), flabby and adequate. Only adequate immune reaction promotes cyclic course and favorable outcomes of the disease.
The scientific achievements of the last years opened new points of view to pathogenesis and therapy of different forms of viral hepatitis. The study of metabolic processes on the level of cell allowed to opeew aggressive components having negative influence on its structure and functions.
The surplus activity of the processes of freeradical oxygenation renders destructive influence on cell’s membranes. As a result free radicals are accumulated in the cells. The process oxygenation of lipids is intensified (peroxide oxygenation lipids – POL). It is known that lipids are the basic structural component of the cells. Antioxydant system of the organism is defending mechanism, supporting free radical oxygenation of the physiological level. Due to investigations of the last years it was shown that activation of the processes of peroxide oxygenation of lipids plays the essential role in the pathogenesis of viral hepatitis and leads to alteration of structure and functions of membrane of hepatocytes, thrombocytes and other cells. It’s worth to underline that simultaneously with activation of POL the considerable depression of antioxydantic activity of the blood serum is marked.
In case of extremely high activity of POL exhaustion of AOS takes place, which leads to disorder of activity of cellular ferments, particullary of glucolysis, glucohenolysis and to rupture of phoshorilation. As a result, cell loses energetic potential. It leads to destruction of cell. Along with this permeability of membrane of hepatocyte and its internal structural components are disturbed. Corrosion of hepatocyte takes place, its synthetic, disintoxicative and other function are lost. Disturbance of permeability of lysosomal membranes causes exit proteolytic ferment into cytoplasm, which complete the death of hepatocyte.
At the last years data about molecular mechanism of the damage of hepatocyte’s membranes were received. It is known that interferones cause depression of reproduction of viruses.
Leukocytaric and fibroblastic interferones may be produced practically by all cells. Immune gamma-interferon is produced by gamma-interferon immunocompetentive cells during immune response.
Interferon may influence to complex of defensive reaction (phagocytosis, inflammation, antigen expression). Interferon is the most important factor of nonspecific resistance. However, interferon has influence to differentiation and activation of effectoric cells of immune system. The activation of monocytes (macrophages), increased generation of peroxide radicals, increased phagocytes activity are observed under influence of interferon. Thus, at the present time interferon is considered not only as antiviral remedy, but also as important regulator of interaction between cells. Due to investigations of the last time it was established that antiviral effect of interferon is not connected with direct interaction with viruses. Antiviral effect is connected with change of metabolic processes in the cells.
It is established that there is decreased produce of interferon in the patients with viral hepatitis B, especially in patient with severe course of the disease. In fulminate course of acute viral hepatitis B interferon is not revealed in the blood serum.
Pathological anatomy
Morphological changes in liver take place in all tissual components – parenchyma, connective tissue, reticuloendothelium, in lesser degree in bile pathway, i. e. diffuse damage of the organs is possessed. Degree of damage fluctuates from insignificant dystrophic and single necrotic changes of epithelial tissue of lobules of liver during light forms till massive and submassive necroses of liver parenchyma. Three variants of acute form of the disease are differentiated: acute cyclic, cholestatic and massive necrosis of liver (Fig.3).
Fig.3. Massive hepatonecrosis
During acute cyclic form diffuse damage of epithelial and mesenchymial elements are observed. Decompensation of beam structure with orderly placement of hepatocytes with their considerable polymorphism is noted.
Along with the dystrophic changes, expressed processes of regeneration with figures of mitosis and abundance of double nuclear cells are determined. Characteristics are presence of scattered necrosis hepatocyties in all lobules. Changes of mesenchymial elements inside the lobules are expressed in proliferation of Kupffer’s cells with their change into macrophages. Cytoplasm of these cells are basophilic, contains bile pigment. Capillaries in the center of lobules are dilated. Proliferation of lymphohistocytary elements with admixtures of plasmatic cells eosinophills and neutrophils are marked in the portal tract. Along with this, reticular hyperplasia of spleen and portal lymphatic vessels is observed. Clinical manifestations of the disease correspond to the severity of destructive changes in parenchyma of liver.
During cholestatic variant of viral hepatitis majority of morphological changes are observed in intrahepatic bile passages with picture of cholangitis and pericholangitis.
Clinical manifestations
Clinical picture of all viral hepatitis is very much similar and differs in percent relation by severity of the course of the disease and its outcomes. Viral hepatitis A and E are characterized by cyclic benign course with complete reconvalescence. In hepatitis B, C and D medium serious and serious course, lingering and chronic forms of disease and lethal consequences are inrarely observed.
Depending upon the expressiveness of clinical manifestations of the disease and degree of functional disorders of liver, established by biochemical tests, light, medium serious, serious and malignant (fulminate) forms of viral hepatitis are differentiated. All atypical cases of the disease (non-jaundice, obliterated, subclinical) are concerned to light forms, because as clinical manifestations and functional changes are weakly expressed in such patients.
During evaluation of severity of the disease expressiveness of intoxication and jaundice is taken into attention along with enlargement of sizes of liver and spleen, loss in weight, level of bilirubin in blood serum.
High intoxication, polyarthralgia, expressed dyspeptic symptomocomplex are typical for fulminate and serious forms of viral hepatitis. Prolonged intensive jaundice, hypotonia, bradycardia, changing into tachycardia, slackness, subfebrile temperature, decrease in diuresis, testifies about serious or even malignant course of viral hepatitis with indefinite prognosis.
Laboratory tests are used for evaluation of severity of disease: tests of concentration of general bilirubin in blood serum of patients, the prothrombin index.
Viral hepatitis have principally cyclic course. Incubation period is different. In hepatitis A it is in average 15-30 days, during viral hepatitis B 30-180 days. The disease begins with signs of general intoxication – so called pre-jaundice period. There are the next some variants of prejaundice period:
1) Dyspeptic variant. – The patients complain of appetite absence, nausea, sometimes vomiting. Temperature is subfebrile. Duration of period is 3-7 days.
2) Astenovegetative variant. – The patients complain of weakness, headache, malaise, decrease of appetite. Body temperature is subfebrile or 37-38 ˚C;
3) Influenza-like variant. – The patients complain of headache, weakness; muscular pain, decrease of appetite. Body temperature 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 principally during hepatitis B and C. Patients complain of pain in joints, sometimes muscular pain is troubling, weakness, decrease of appetite. During this subfebrile temperature is in majority of the patients. Duration of this period is composed of 7-14 days;
5) Mixed type – All above indicated signs of intoxication are of different degree.
The next period of the disease is climax period. The state of the majority of the patient becomes better. The temperature is normalized, urine becomes dark, colorness stool. Scleras are icteric, jaundice grows gradually (Fig.4). The further course of the disease depends on degree of liver damage by the virus, which determines the severity of the disease. During light course of viral hepatitis jaundice grows in a period of 3-5 days. It is present on one level during one week. Disappearance of jaundice is observed on 15-16 day. Urine becomes more light at the end of the first-second week of the jaundice period, it is of yellow or orange color.
During medium serious and serious course of the disease yellowish coloring of scleras and skin is more intensive, jaundice period is prolonged (20-45 day). In majority of the patients the signs of cardiovascular system disorder are observed. There are hypotonia, bradycardia, muffed hearts sounds. In 80-90 % of the patients liver is enlarged, its surface is smooth, borders are curved, moderately painful. In 30-40 % of patients spleen is palpated. During serious course of viral hepatitis in some patients meteorism of abdomen, caused by disorders of digestion (signs of damage of pancreas, secretory glands of stomach and disorders of biocenosis of gastro-intestinal tract) is observed. In some patients jaundice is very intensive (Fig.5) and skin itch is observed (so called cholestatic variant of the course of the disease).
Fig.4. Icteric sclera
Different changes are observed from central nervous system. Already during light course of viral hepatitis changes adynamia, slackness, disorders of sleep may be present.
In serious cases clear cerebral disorders caused by considerable dystrophic changes in the liver, endogenic intoxication and increase of the activity of the processes of POL are observed.
In the period of reconvalescence reverse development of symptomatic of disease, normalization of biochemical indices is marked.
Fig.5. Jaundice of skin
Complications
The most threatening outcome of viral hepatitis is acute or subacute massive nercosis of liver, during which picture of acute or subacute hepatic encephalopathy is observed. An acute hepatic encephalopathy (AHE) is typical for acute hepatites.
The term “acute hepatic encephalopathy” denotes unconscious condition of the patient with violation of reflex activity, convulsions, disorder of life vital functions as a result of deep brake of action of cerebral cortex with its spread on to subcortex and below laying parts of central nervous system. This sharp brake action of nervous-psychic activity is characterized by disorder of movements, sensibility, reflexes and by absence of reactions on different irritators.
Hepatic coma is an endogenic coma, caused by endogenic intoxication as a result of loss of function and breakdown of liver.
There are the next stage of AHE – precoma I, precoma II and properly coma.
Precoma I is characterized by non constant disorder of consciousness, unsuitability of mood, depression, lowered capability towards orientation, tremors, inversion of sleep. Patients are irritated, sometimes – euphoric. They are troubled by paroxysms of depression, doom, presentiment of death. Fainting, short time unconsciousness, giddiness, hiccup, nausea, vomiting may be observed. Jaundice grows. Bradycardia is changed by tachycardia. Tendon reflexes are raised. Such condition prolongs from few hours to 1 – 2 day with moving into second stage.
In the second stage of precoma consciousness is more hampered, losses in memory is a characteristic feature, alternated with attacks of tachymotor and sensory exciment till delirium. During awakening orientation in time, space and action is absent. Tendon reflexes are high. Jaundice raises sharply. Muffed heart sounds, tachycardia, hypotonia are revealed.
Rhythm of respiration is disturbed. Liver begins to decrease in size. Hepatic insufficiency is inrarely accompanied with hemorrhagic syndrome due to development DIC-syndrome. In 1/3 of patients nasal hemorrhages, gastrointestinal hemorrhages, uterine bleeding and hemorrhages of other localization are observed. Diuresis decreases. Abdomen is inflated; peristaltic of intestine is decreased. Such condition continues for 12 hours – 2 days.
During the third stage – properly coma – complete loss of consciousness and disappearance of reflexes is marked. Pathological reflexes may be too. Rigidity of muscles of extremities, hyperkineses, convulsive syndrome, and thereafter complete areflexia are observed. Expressed tachycardia, hypotonia, disorder of rhythm of respiration are revealed. Diuresis decreased considerably till anuria. The death of the patients is through 6-24 hours. The patients perish from massive hemorrhages or in development of severe metabolic acidosis.
Diagnosis
Preliminary diagnosis of viral hepatitis is based on epidemiological anamnesis, finding of the development of the disease, clinical picture with account of peculiarities of the ways of the transmission, duration of incubation period, presence of prejaundice period, presence of typical subjective and objective signs with account of the patients age.
Diagnosis is confirmed by routine and specific laboratory tests. In routine blood test of the patients with viral hepatitis lymphocytosis is observed with moderately expressed course and in serious course of the disease – anemia and leucopenia. ESR is slightly decreased. In urine urobilin and bile pigments are observed. During climax period, particularly during medium serious and serious forms, there are no stercobilin in stool.
Increased content of general bilirubin, primarily on account of its direct fraction is observed in blood serum during all jaundice period. Ratio of direct and indirect fraction composes 3:1. In all patients already in pre-jaundice period of the disease, during all jaundice period and in the period of early reconvalescence increased activity of ALT, AST is observed, testifying about the presence of cytolytic processes in liver.
Specific antigens (HBsAg) and antibodies to antigens of all known at present time viruses of hepatitis are revealed in the blood of patients with help of these methods. Discovery of antibodies of class of IgM testifies about acute disease. Discovery of other classes of immunoglobulins antibodies testifies about lingering or chronic course of viral hepatitis or about earlier infectious process or about disease in the past.
Differential diagnosis
Differential diagnosis of viral hepatitis is necessary to perform with diseases like leptospirosis, yersiniosis, mononucleosis, malaria, mechanic and hemolytic jaundice, toxic hepatoses.
Leptospirosis is characterized by acute beginning of the disease, often with chill, continuation of fever during of climax of the disease and jaundice, pain in muscles, especially in calfs, hemorrhagic syndrome. In blood leucocytosis with neuthrophillosis and shift in the formula to the left, accelerated ESR are observed. Activity of ALT and AST is moderately raised or normal relation of direct and indirect bilirubin 1:1. In blood serum concentration of urea and residual nitrogen increases. Stool is colored. In urine erythrocytes, leukocytes, like wax cylinders are marked in large quantity. Diuresis decreased till anuria.
In generalized forms of yersiniosis jaundice may be also observed, however it is accompanied by fever, metastatic focuses in other organs and tissues, leucocytosis with nuetrophilosis, accelerated ESR, aggravations and relapses. Diagnosis is confirmed by serological methods with specific yersiniotic antigen.
In malaria there are clear alternation of attacks fever with chills, replaced by heat and sweat and periods of apyrexia. Often painful, increased in size spleen is marked. In blood hemolytic anemia, in fat drop blood and smear different forms of malarial plasmodia are reveled. In blood serum indirect fraction of bilirubin predominates.
In mechanic jaundice stones in gall bladder and bile passages, enlargement of head of pancreas and other signs are revealed with help of ultrasound investigation. In majority of the patients moderate increase of activity of ALT, AST, leukocytosis, accelerated ESR are marked. Hemolitic jaundice is characterized by anemia, accelerated ESR, increase of indirect fraction of bilirubin. Stercobilin is always present in stool.
Differential diagnosis of VH with hepatoses is complicated and demands from doctor thoughtful and painstaking work. During this essential significance possesses correctly taken anamnesis.
Outcomes of the disease
Viral hepatitis most often ends with complete reconvalescence. In some patients may be cholecystitis, cholangitis, pancreatitis, dyskinesia of bile excreting pathways after an acute hepatitis. In 5-10 % of patients lingering course with periodical aggravations, caused by prolonged persistence of virus is observed. In such cases chronic hepatitis develops. This variant of the course of the disease is typical of viral hepatitis B and C chronic hepatitis may end up by liver cirrhosis.
Treatment
Treatment is used complex and depends on the clinical form and gravity of disease current. At mild current of a viral hepatitis in the acute period it is possible to prescribe only semi-bed regime, diet № 5, polyvitamines and desensitizing preparations: calcium gluconate, Diazolin, Diprazin or Tavegil. In case of meteorism, feeling of gravity in epigastrium area after the meal, unstable feces – Festal, Pancurmen, Allochol, Cholenzym are indicated.
At medioserious and serious current of the acute form of hepatitis a bed regime is provided together with the specific treatment. Desintoxication therapy consists of plentiful drink; 5 % solution of glucose, saline solutions, Ringer’s solution, Trisault, Quartasault, 20 % solution of Sorbit (or. Sorbitoli), donor Albumin (given in vein), one of enterosorbents SKN of different brands, carbaphosfer, Carbosilan, Sillard P, Enterosgel, Polyphepan. The quantity of drunk liquid should be balanced with a daily urine. Polarizing admixture: 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 improving metabolism in hepatocytes: Ascorbinic acid, Thiamin chlorid, Pyridoxine hydrochloride, cocarboxylase, Potassy Orotat, Riboxin, Citochrom C, Lipamid, Calcy Pangamat. Last two preparations are indicated mainly at accompanying hepatoses with fatty infiltration of liver (alcoholism, diabetes, thyrotoxicosis, an obesity etc.). For acidosis decreasing 2 % solution of sodium of a hydrocarbonate 25-50 mL (P.R.) 3-4 times per day or on 150-200 mL (I.V.) should be infused.
Among etiotropic agents moderate medical effect at acute virus hepatitis has human recombinative α-2-interferon – Reaferone, Intron A, Realdironi or analogue Laferone in powder, in amp. 1 000 000 IUN: from 1-st to 5-10-th day of the icteric period. Next days their efficiency falls. At acute hepatitis B Laferon is infused 1 000 000 IUN 2 times per day during 5-6 days, then 1 000 000 IUN 1 time per day during 5 days. If medical effect is insufficient, there should be continued infusing 1 million UN 2 times per week during 2 weeks. It is worthy to use Leicinferone as the basic component which is the admixture of natural α-interferons of donor leucocytes, the factor of necrosis of tumours and Interleicin-1. However many clinicians challenge expediency of indication of interferon at the hepatitis of acute period. More physiologic is the stimulation of endogenic interferonogenesis with the help of such inductores, as Mefanam acid, Prodigiosan, Pyrogenal, Nifluril, Cycloferon.
At threat of hepatonecrosis – glucocorticoids 150-200 mg are prescribed. The dose of prednisolon per day, must be reduced after the patient gets out of extremely serious condition. The volume of infusion solutions is enlarged up to 30-50 mL/kg per day. Ornithin (ornicetyl) promotes a linkage and removing out of organism nitrous bonds and improves a metabolism.
A lactulose reduces an adsorption of ammonia from intestine in blood, especially in combination with Neomycin. With the aim of oppression of processes of an autolysis there should be used inhibitors of proteolytic enzymes Contrical or Gordox each 8 hours (I.V.) intravenous dropping, at improvement of a condition synthetic inhibitors. At retention of liquid in organism it is required to use Spironolacton (Veroshpiron), Kaliumsaving diuretics, or saluretics-Furosemid, Etacrinic acid. Psychomotor exaltation is stopped by Sody hydroxybutyrate in combination with Sibazon (Seduxen), Haloperidol. At increasing of hepatic failure there are used antilymphocytic gamaglobulin during 1-5 days with the control of quantity of lymphocytes in a pereferic blood, apparatus methods of clearing of patients blood, hyperbaric oxygenation.
At cholestatic form of a virus hepatitis the are effective preparations which form complexes inside intestine with cholic acids which caot be soaked up, cholestiramin and Bilignin. Fenobarbital is used which is the inductor of synthesis of Glucouroniltransferas. This enzym is necessary for conjugation of bilirubin with glucuronic acid, and stimulating its egestion with bile. Fenobarbital is indicated with combination of Cyanocobalamin. Simultaneously for intensifying secretion of bile Nospan and Cholenzym are indicated. After the termination of an acholia duodenal tubages 5-10 % solution of magnesy sulfat (1/4-1/2 glasses), Sorbit or Xilit (20 gr on 100 mL of hot water) 1 hour before breakfast are applied.
Bioflavonoids – Convaflavin, Carsili, Legalone, Silibor, Quercetin are indicated in case of the alonged reconvalescence. At hyperaminotransferasaemia – Aevit or Tocopherol acetas, Thymalin, T-activin, Dipiridamol (Curantyl), Isoprinosin (has also antiviral property) – give positive effects. There are used also Saparal, Methyluracil (or. Methacil), Natry nucleinic, Thymalin in a combination with Dipiridamol, Hofitol.
Cholagogue agents – broths of flowers of immortele, hips, thyme, mints peppery at the rate of 1 dining spoon of a herb or a mixture to 1 glass of water are indicated for convalescents Fenobarbital with Cyanocobalamin are applied during 10 days in case of hyperbilirubinemia with prevalence of untied fraction of pigment; preparations of choice can be Cordiamin or Sibazone (Seduxen) which also stimulate glucoruniltransferase of hepatocytes. At hyperbilirubinemia mainly at the expence of connected fraction stimulate a bile secretion using oxygen cocktails with cholagogue herbs and honey. Vitohepat or Cobamamid stimulate neogenesis and hemopoes, accelerate regenerative processes in liver, course of treatment lasts 15-20 days. At astenia and hypoproteinemia, and also for elimination of catabolitic influences of glucocorticoids which were used at the acute period, anabolic hormones: such as methandrostenolon (Nerobol), Phenobolin (Nerobolil) or Retabolil are indicated. For elimination of the asthenic phenomena, there are used Novopasit, tinctura of Valeriana root (20 gm: 200 mL), herbs of neetle, Thyme, Bromidums, and in rather serious cases – Chlozepid (or. Eleny), Sibazon (or. Seduxen), Relany, Barbiturates.
At the dyspeptic phenomena caused by oppression of secretory function of digestion organs, also Allochol, Liobily, Cholenzym, Festal, Panzynorm forte, Pancurmen, Pancreatin, Pancitratit, Vobensym are widely used.
At posthepatitic hepatomegalias without signs of cytolisis it is not reasonable to indicate Lydase – promoting a resorption of a fibrous tissue, 10 injections every 2-nd day. It can be infused only after exception of inflammatory process in hepatobiliar ways (will carry out control duodenal intubation).
Chemotherapeutic preparations are indicated in case of the bacterial cholecystitis. At mild current of disease it is possible to use only a fortnight course of Nicodin, at appreciable changes antibiotics or Nitrofurans preparations are indicated.
It is possible to make antibioticosensetivity of microorganisms allocated from bile. For definition there are used mediums, which content bile of the patient as it influences on essentially activity of antibiotics. Use Ampicillin, Carbenicilin Dinatry salt, Erythromicin, Cefazolin, Furazolidone, Furagin, at Candida infection sody salt of Levorin. Chemiopreparations indicate in average therapeutic doses during 7 – 8 days.
Specific therapy of chronic virus hepatitises is carried out by preparations of α-interferon (Intron A, Roferon, Realdiron, Reaferon, Laferon). They are effective in case of low replicative activity of the virus determined in blood virus DNA (HBeAg) at a hepatitis B and virus RNA at hepatitis C. The additional indication is high activity of serum Alanineaminotransferase. One of the specified preparations inject (I.M.) or subcuteneous 3 – 5 million IUN per day 3 times per week during 6 months. Treatment should be stopped, if positive results were not observed after 3 months. The positive effect is observed at 40-50 % of patients with hepatit B and at 20-30 % of patients with hepatit C. At chronic hepatit D less than 10 % of patients are released from viruses even if treatment lasts 1 year. In some cases the success of immunotherapy of virus hepatitises may be increased if preliminary indicate short course of treatment about 6 weeks of glucocorticoids. Combined usage of interferon and Thymalin, Essentiale, Lamivudin, Chenodesoxycholyc acids has been proved.
The side-effects of α-interferon are noticed at half patients right after injection, among them are headache, fever, myalgia, arthralgia, general delicacy. They can be prevented by means of analgetics. Among the remote side-effects are: nausea, diarrhea, depression, irritability, leuco- and thrombocytopenia. Decreasing of a dose of preparation allows to weak these disorders. There are serious complications (sepsis, psychosis, autoimmune diseases), that demand an immediate cancellation of interferonotherapy.
At chronic hepatitis B in a phase of replication there are applied a peroral preparation Lamivudin (Zeffix). It provides the same level of seroconversion, as standard course of treatment by interferon.
At chronic hepatitis with low replicative activity of a virus preference is given to pathogenetic agents improving metabolic and reparative processes in liver, such as: Silibor, Carsil, Liv-52, Hepatofalk, Planta, Hepabenne, Antral, Tocopherol Acetat etc.
Prophylaxis
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If the patient is hospitalized, he should be placed in a private room with separate toilet facilities. The major reason for such isolation is to prevent the spread of type A hepatitis. Even with lax precautions, such spread is very rare; most patients with type A hepatitis are no longer excreting virus once they have become symptomatic. Nevertheless, there are exceptions, and isolation is prudent. Secretions and blood products should be handled with care gowns, masks, and gloves are not necessary, but a prominent sign reading “needle and blood precautions” is appropriate. Labeling of blood specimens from a patient with hepatitis, is a common practice. It should be stressed, however, that all blood from any patient should be handled as if potentially infectious.
If the patient with viral hepatitis is at home, the patient should be advised about care in personal hygiene – careful hand washing. Attention also should be paid to blood and blood products and the handling of cuts and lacerations.
Recommendations regarding the prevention of acute hepatitis are governed by the type of viral hepatitis that is being considered. In the case of acute type A hepatitis, all family members, and close personal contacts should receive immune serum globulin (ISG) at a dosage of 2-5 mL in as soon as possible after exposure. Office, factory, and school contacts do not need to be treated. Immune serum globulin can be given for up to 4 weeks after exposure, but it probably is only effective if given within 7-14 days.
In the case of acute type В hepatitis, prophylaxis only needs to be provided for “regular” sexual contacts. The best form of protection is argued Hepatitis В immune globulin (HBIG) at a dosage of 5 mL in as soon as possible and again 1 month later has been the conventional recommendation in this situation. However, the efficacy of HBIG in preventing the sexual spread of acute type В hepatitis has not been well proved. In addition, there is now evidence that postexposure immunization with HBV vaccine, can attentuate or prevent acute type В hepatitis. Vaccine should be given as soon as possible and then 1 month and 6 months later.
AQUIRED IMMUNODEFICIENCY SYNDROME
(AIDS/HIV infection)
http://www.cdc.gov/globalAIDS/default.html
A secondary immunodeficiency syndrom caused by a virus and characterized by severe immune deficiency resulting in opportunistic infections, malignancies, and neurologic lesion in individuals without prior history of immulogic abnormality.
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History
In June 1981 the Morbidity and Mortality Weekly Report carried a report of five deaths due to overwhelming Pneumocystis carini pneumonia in Los Angeles, California. P.carini has been recognized for many years as a human opportunist infection, infrequently causing life threatening pneumonia in patients with naturally occurring or iatrogenic immunosuppressant. Since the development of immunosuppressive regimens for overcoming transplantation rejection, Pneumocystis has been seen in patients with compromised cellular immunity. All of the five patients reported had been homosexual men with no prior illness or history of congenital immunodeficiency, and none had taken know immunosuppressive drugs. In December 1981 three reports in the New England journal of Medicine described the medical presentation and laboratory characterization of a further 20 homosexual men who had died of unexplained immunodeficiency. In every case previously healthy young men had developed overwhelming opportunist infections associated with profound cellular immunodeficiency, or Kaposi sarcoma, a tumor previously associated with immunosuppressant. All the patients had an absolute decrease in the number and proportion of CD-4 T-lymphocytes, and a specific loss of T-cells immunity. The syndrome was initially termed «gay – related immune deficiency» ( GRID), but by the end of 1982, cases of this acquired immunodeficiency had been reported in intravenous drug users, female sexual partner of index cases, children of affected woman and in heterosexual men and woman from Haiti resident in the US. As this disease was clearly not linked exclusively to homosexuality, the term acquired immunodeficiency syndrome (AIDS) was adopted.
From early 1982 onwards, efforts to identify the causative agent intensified and in may 1983 group from the institute Pasteur, Paris, reported the isolation and propagation of a T-lymphotropic retrovirus, lymphoadenopathy associated virus, LAV from the lymph node of a patients with persistent lymphoadenopathy, a syndrome know to be assotiated with, and preceding the development of AIDS.
Etiology
Retroviruses are very small viruses composed of a single strong of RNA, the intermediate nucleic acid in the production of proteins (Fig. 1). Normally, the flow genetic information starts with a piece of DNA, which makes a piece of RNA, which in turn codes for, protein. Everything flows in that direction. Retroviruses contain a unique enzyme called reverse transcriptase, which allows this single strand of RNA, that is, the virus, to make itself back into a piece of DNA, going backward against the flow of genetic information. Hence, «retrovirus». This piece of viral DNA than inserts itself into the genetic material of the cell that it is infecting, in this case the helper T-lymphocytes, and it remains intertwined there for the life at the cell.
Fig.6. HIV retrovirus
The emergence of a new infections agent in a human population can have only a limited range of explanation; either the infection was previously in an isolated human population from which it had been exported though some societal change, or else it might have been a zoonosis newly exposed to human transmission. A third line of explanation, that of an extraterrestrial or even a man-made origin, has been popular with conspiracy theorists, but will not be furthers discussed. The natural history of HIV 1 infection is marked by the long period of time between infection and disease.
Epidemiology
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The major transmission routes of human immunodifficiency virus are sexual contact, parenteral exposure to blood and blood products and perinatal transmission. early in the AIDS epidemic, epidemiological studies establish that receptive rectal intercourse was the predominant mode of HIV-1 acquisition by homosexual man. Other practices that could traumatize the rectal mucosa appeared to increase further the infection risk for the receptive partner. Insertive rectal sex could also place a men at risk for HIV-1 infection, although the insertive partner would be at lower risk than the receptive partner.
On a world-wide basis sex between man and women apparently is the most common mode of acquiring HIV-1 infection heterosexual transmission accounts for the vast majority of cases. In other country where AIDS cases attributed to heterosexual transmission, although still a small percentage of the total number of reported cases comprise the most rapidly growing category. Therefore an understanding of the rate at which HIV-1 is transmitted between heterosexual couples and of the factors that may impede or enhance heterosexual transmission is important in slowing the worldwide HIV-1 epidemic.
In the country, where HIV-1 infection is more common in men than women, studies of female-to-male transmission of HIV-1 infection are both fewer and smaller than studies of male-to-female transmission. Available date suggest female-to-male transmission may be less efficient than male-to-female transmission.
Overall these American and European studies suggest that heterosexual transmission from HIV-infected persons to their regular sex partner is relatively inefficient, especially female-to-male transmission. Furthermore, the risk of heterosexual transmission is not related simply to the number of episodes of sex with HIV-infected person because some people have remained uninfected after hundreds of such contacts whereas others have become infected after a single episode of intercourse.
Infectivity may be higher during early infection before the development of antibodies to HIV-1, also genital ulcer diseases and inflammation of the genital tract lead to increased susceptibility to HIV infection.
Mother-to-infant transmission of HIV apparently is relatively efficient; without treatment approximately one in the four infants born to seropositive mothers is infected. With one rapid spread of infection to women of reproductive age perinatal transmission is now a major consequence of HIV epidemic. The precise rate of perinatal transmission in a given setting has been difficult to define because of problems in the infant and the difficulties in maintaining long-term follow-up. Uninfected children born to seropositive mothers may retain passively aquired maternal antibody for 6 to 18 months.
Extensive laboratory research and epidemiological studies indicate that HIV is not transmitted by shaking hands, hugging, kissing, contacting bodily secretion such as sweat, mucus (as in sneezing or coughing) or salive. Nor is HIV transmitted by food, swimming at a pools, drinking at a water fountain and also bloodsucking mosquitoes or other arthropods.
Pathogenesis
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Following infection across a genital surface, involving infection of CD-4/CCR 5 bearing cells in the mucosa or submucosa, the virus presumably migrates to a regional lymph node, where viral replications occurs. A number of rounds of viral replication than occur within the bounds of the regional lymph node as no detectable virus or immune respons occurs for up to 42 days post infection. When the quantity of infected cells exceeds a threshold, viremia occurs, and the symptoms of an acute non-specific viral illness with tende adenopathy, sore troath, diffuse macular rush, arthralgia and fever. Following the acute viremia, when up to 107 viral particles /ml plasma can be found, a primary immune response develops with antibodies to viral proteins and a cytotoxic T-cells response, which limit viral replication and clear viral particles from the plasma. The reduction the viral load in plasma is not matched by a clearance of provirus in peripheral blood mononuclear cells, and cellular viremia continues in the face persistent and sustained cellular and humoral immune response for the duration of the infection. Even while plasma viral load is suppressed by the immune response, CD-4 T-lymphocyte number foll in linear manner over time. The most plausible explanation for the pathogenesis of AIDS over time is the sustained less CD-4 cells by ongoing HIV viral replication iature peripheral blood T-cells and by a slight failure of production of match peripheral destruction of HIV CD-4 cells. However, recent controversy over the pathogenic mechanisms and homestasis of T-cells has revealed that simple viral cytopatphic effect on CD-4 cells may be overly simplistic model.
During the course of HIV infection, CD-4 cells continue to decline in peripheral blood and plasma viral load slowly rises. Over a definite period CD-4 cells number declines from a 800 to 200 ml; at this level, the probability of the cellular immune system containing latent or environmental infections such as P. carinii falls and clinical opportunist infection becomes increasingly possible. As the viral load rises. HIV isolates with altered co-receptor usage appear which can use the CXCR-4 chemocine receptor rather than CCR-5; these isolates are more cytopathic in vitro, and may lead to wider tissue distribution of HIV in later disease, AIDS is therefore, the clinical condition of an immune system which is sufficiently compromised by HIV infection that there is an inability to protect against the growth of low grade pathogenes or viral indeced tumors.
The fact that this virus, after infection of the host, besides destroyed strong immune system also can spread to many body tissues. The ultimate outcode of the infection depends on the host’s immune reaction to the virus either through suppression of HIV replicationor through killing of the infected cell. in some individuals an active immune system has prevented development of the disease for years. The factors important in maintaining this immune response are not yet know and merit close attention. The immune deficiency produced by HIV infection makes patients suseptible to infection by a variety of organisms, including viryses, bacteria, fungi and parasites that are of low pathogenecity in the normal individual and of variable prevalence in different part of the world. In some individuals the immune system appears to make enhancing antibodies to HIV and this phenomenon occurs particularly with progression of disease. It is related to change to antibodies made and in some cases to modifications in the virus so that is more sensitive to enhancing antibodies. Moreover, the immune system can hyperreact, with production of antibodies that might also hasten the development of disease. Clearly changes in the virus and the immune response of the host play important roles in the ultimate steps leading to AIDS.
Clinical manifestations
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The time from exposure to HIV until the onset of the acute clinical illness is typically 2 to 4 weeks, although longer incubation period have been reported. The clinical illness is acute in onset and lasts from 1 to 2 weeks. It can be associated with an appreciable degree of morbidity and patient may require hospitalization. The main clinical features of primary HIV infection reflected both the lymphocytopatic and neurologic tropism of HIV. Patients report fever, lethargy, fatigue, headaches, retro-orbital pain, sore throat, muscular pain, occasional diarrhea, maculopustular rash and the onset of swollen lymph nodes (swollen glands). Meningoencephalitis may also occur. Lethargy and malaise are frequent, often severe and may persist for several months after resolution of the other clinical manifestations of primary HIV infection. Lymphoadenopathy develops in approximately 70% of persons, generally in the second week of the illness and usually concomitant with the development of peripheral lymphocytosis, reflects the fact that HIV has activated B-lymphocytes to become plasma cells and secrete HIV antibodies.
Fig.7. AIDS lymphoadenopathy
The lymphoadenopathy may be generalized, but the occipital, axillary and cervical nodes are most commonly involved (Fig. 7). The lymph node enlargement persist after the acute illness bat tend to decrease with time. Splenomegaly has also been reported. The mechanism for this splenomegaly is not apparent; it may be related to increased clearance of virally infected lymphocytes. The most frequently reported dermatologic evidence of primary. HIV infection is an erythematous, nonpruritic maculopapular rash. This rash is generally simmetric, with lesions 5 to 10 mm in diameter, and affects the face or trunk, but it can also affect the extremities including the palms and soles, or can be generalized. Other skin lesions noted during primary HIV infection include a roseola-like rash, diffuse urticaria, vesicular, pustular exanthema and enanthema, desquamation of the palms and soles and alopecia. Mucocutaneous ulceration is a distinctive feature of primary HIV infection. Ulcer have been reported on the buceal mucosa, gingiva, or palate, esophagus, anus, and penis. They are generally round or oval and sharply demarcated, with surrounding mucosa that appears normal. The tongue of patient showing the characteristic symptoms of thrush. Note the milk-white flakes of C. albicans on the tongue surface. An unexplained incident of thrush is often considered an early sign that HIV infection is present. Patients also experience weight loss of as much as 10 % of baseline body weight or more. Constant low-grade fever and diarrhea extending over several weeks. In addition, the fatigue may be so overwhelming that patients cannot lift their heads from the pillow on waking in the morning. One of the most troublesome aspects is the night sweats. Individuals perspire so heavily at night that the bed linens and nightwear become drenched with sweat. Saturation can be extensive enough to require linen changes, and sleep is fitful at best. Few other microbial diseases are accompanied by such heavy sweating.
The isolation of HIV from cerebrospinal fluid (CSF) during primary HIV infection indicates that infection of the central nervous system (CNS) occurs soon after exposure. Elevated neopterin and β2-microglobulin levels have also been found in CSF during primary HIV infection both in individuals with and without clinical meningitis, suggesting that the cellular immune system in the CNS may be activated during this stage even without the development of overt neurologic symptoms or signs. The most commoeurologic symptoms are headaches, retro-orbital pain (particularly during eye movement) and photophobia. Several cases of aseptic meningoencephalitis during primary HIV infection have been reported.
Prolonged infection with HIV is often completely asymptomatic; however, a minority of patients complain of nonspecific constitutional symptoms in the month or years after primary infection. Patients commonly complain of being easily fatigued and report the need to reduce their normal activities somewhat. In patients with more advanced HIV disease and severe de pletion of CD4 cells, constitutional disease may primarily reflect immunosupression or may herald the onset of opportunistic infections or malignancies. Patients with progressive constitutional symptoms should be evaluated carefully for opportunistic pathogens. A history of respiratory, neurologic, gastrointestinal and dermatological symptoms should be elicited and a thorough physical examination completed.
In the late stages of HIV infection when immune defenses have been severely compromised and systemic complications have begun to accumulate, the nervous system becomes highly susceptible to a wide array of disorders involving all levels of the neuraxis, including meninges, brain, spinal cord, peripheral nerve, and muscle.
Systemic lymphoma complicating HIV infection may secondarily to the central nervous system involving the meninges, clinical manifestation may be cryptic but usually include cranial nerve palsies, head aches, or increased intracranial pressure.
From an early stage it become clear that the nervous system was frequently involved in HIV infected patients. Among the severe and life-threatening infections experienced by those with immune deficiency were brain abscesses due to toxoplasmsis. As other neurologic manifestations emerged without signs of recognizable opportunistic infection it became clear that HIV was probably directly neurotropic as well as lymphotropic.
Toxoplasma gondii is an obligate intracellular parasite for which the primary host is the cat. Humans may acquire it from the cat by the fecal-oral route. in man primary infection is usually asymptomatic unless congenitally acquired. The organism forms cysts in all tissues which persist for life and are the source of recrudescent infection in the compromised host. Infection in the brain is usually multifocal as old encysted parasites become actively pathogenic again. The clinical presentation may be focal or diffuse but is a cerebrovascular accident, but is more usually progressive aver a few days or a week or two.
Peripheral neuropathies of several types can complicate the various stages of HIV infection. Early in the course of HIV infection a Guillain-Barre type of neuropathy may be seen. The clinical picture is the same as the familiar acute inflammatory or postinfectious neuropathy, with weakness of limb and facial muscles, minor sensory symptoms and loss of tendon reflexes. The weakness tends to be both proximal and distal. There bay be backache and limb pains. There is evidence that the axonal neuropathy in the late stages of the disease correlated with the presence of dementia. Its ethnology is unknown, but it has been suggested that it may be a direct effect of HIV.
The most prevalent opportunistic disease among persons with HIV in late stage is Pneumocystis carinii pneumonia. Recently, however, studies of ribosomal RNA of P. carinii have shown that phylogenetically the organism is most closely related to the Ascomycetes (yeasts): thus P. carinii should probably be considered a fungus rather than a parasite. This reclassification has little clinical relevance but may suggest new therapeutic approaches and culture techniques. P. carinii is thought to have a life cycle consisting of three stages: cyst, whish are spherical or crescent-shaped form 5 to 8 mm in diameter; sporozoites or intracystic bodies, found only within the cyst; and tropozoites, found outside the cyst and believed intermediate between the sporozoite and the cyst. The Giemsa stain is taken up by both the intracystic sporozoites and extracystic tropozoites; cyst are not pozitively stained and cannot be seen except as negative images within the matrix of a clump of tropozoites. Infection with P. carinii is common early in the life and dose not generally results in symptomatic disease in immunocompetent hosts. Until the occurrence of the epidemic of infection with the HIV P. carinii pneumonia was an uncommon, sporadic disorders that occurred primary in patient with leukemia or other recognized causes of impairment of host defences and in patients who were given immunosuppressive therapy. Several studies in the United States have shown that circulating antibodies to P. carinii develop in mot children by age 2 to 3 years, leading to the conclusion that asymtomatic infection with P. carinii is nearly universal at least in the areas where these studies were conducted. Patients with P. carinii pneumonia usually have had non-specific symptoms such as fever, fatigue, and weight loss for weeks to months before developing respiratory symptoms and often have other HIV-related disorders that indicate severe immunosupression. The most common presenting symptoms of P. carinii pneumonia are fever, non-productive cough, and progressive shortness of breath. IN patient with P. carinii pneumonia chest radiographs most often show diffuse interstitial infiltration involving all portion of the lungs. Several variations may be seen. The infiltration may be heterogenously distributed throughout the lung, or it may be miliary in appearance. Diffuse or local air-space consolidation may also be noted. In patients who are being given aerosol pentamidine prophylaxis, focal upper lobe infiltration are relatively common. Cystic changes or pneumatoceles may occur, especially during the healing process, and cavitation withing pre-existing nodular lesions has been described. Probably as a result of the cystic or cavitary processes, spontaneous pneumothorax may occur. Pleural effusion and intrathoracic adenopathy are very uncommon with P. carinii pneumonia.
Since the beginning of the HIV epidemic an increasing association of Mucobacterium tuberculosis infection with HIV infection has beeoted. Between 1978 and 1985 the yearly rate of tuberculosis more than doubled at one New York City hospital. Although the pathogenesis of most HIV associated tuberculosis appears to involve reactivation of latent M. tuberculosis infection, the clinical presentation is generally typical of reactivation tuberculosis only for those patients whose immune function is still relatively intact, whereas that of patients with HIV is much more typical of progressive primary tuberculosis. Only one-third to one halt of HIV-associated tuberculosis is confined to the lungs. The most frequent radiographic manifestations of pulmonary tuberculosis in patients with HIV are hilar or mediastinal adenopathy or both and localized infiltrates limited to the middle or lower lung fields. Pulmonary cavitation is rarely seen. The classic radiographic picture of apical infiltrates in the absence of hilar or mediastinal adenopathy has been reported in less than 10 % of HIV-associated cases. One half to two thirds of HIV-related tuberculosis involves extrapulmonary sites (with or withoutpulmonary involvement). Perioheral lymph nodes and bone marrow are the extrapulmonary biopsies but rarely in pulmonary biopsies. Other extrapulmonary sites that have revealed M. tuberculosis include urine, blood, bone, joint, cerebrospinal fluid, liver, spleen, skin, gastrointestinal mucosa and ascites fluid. Two extrapulmonary tuberculosis syndromes described in HIV patients are of particular interest: M. tuberculosis bacteremia and central nervous system mass lesions. On the other hand, tuberculosis in patients with otherwise asymptomatic HIV infection usually is clinically similar to tuberculosis in immunocompetent hosts.
The association of disseminated Mycobacterium avium complex (MAC) infection with HIV was recognized early in the HIV epidemic. Disseminated MAC infection has been reported only rarely in patients without HIV. Disseminated MAC infection occurs exclusively in patients with very advanced HIV disease essentially only in patients with CD4 lymphocyte counts<100/ml. MAC is a ubiquitous soil and water saprophyte. The source of MAC invasion in HIV patients may be gastrointestinal or respiratory. The presence of large clusters of mycobacterium within macrophagas of the small bowell lamina propria suggests the bowel wight be the portal of entry. However, respiratory isolation of the MAC also frequently precedes disseminated infection, suggesting MAC infection may begin in the lungs as well. Since most HIV patients with disseminated MAC infection have other concomitant infections or neaplasms and since MAC appears to cause little histopathologic evidence of inflammatory response or tissue destruction, the relationship between constitutional symptoms, organ dysfunction, and MAC infection has been uncertain.
Four clinical syndromes often over lapping, have been associated with disseminated MAC infection.
· Systemic symptoms. Fever, malaise, weight loss often associated with anemia, neutropenia.
· Gastrointestinal symptoms.
· Chronic diarrhoea and abdominal pain (MAC infection of colon often observed at autopsy)
· Chronic malabsorbtion (histopatologic changes in small intestine similar to those with Whipple’s disease often observed at autopsy)
Extrabiliary obstructive jaundice secondary to periportal lymphadenopathy.
Cryptococcus neaformans and tuberculosis are the major opportunistic infection complicating the HIV epidemic world-wide. Although other pathogens may dominate on individual continents or in specific regions, no other major pathogen poses as great a global threat to those immunocompromised by HIV infection. The high mortality and morbidity rates associated with cryptococcal infection and the toxicity of traditional therapy have sparred intense interest iew treatment alternatives. A better understanding of the natural history of HIV-mediated immunodepression has seen the emergence of debate about the use and advisability of fungal prophylactic. This organism a common resident of the lung, is often inhaled from the air. It grows actively in the droppings of pigeons and enters the air in wind borne particles. The fungus is generally noninfectious, but in patients with HIV it multiplies in the lungs, spreads to the blood and localized on the brain and its coverings. The clinical presentation of cryptococcal disease in HIV patient is often subtle and nonspecific. A prolonged febrile prodrome, indistinguishable from that accompanying other opportunistic infections is common. Frequently no localizing signs or symptoms are present to guide the physician toward the diagnosis of cryptococcal disease. Although the portal of entry for C. neoformans is the lung. Pulmonary cryptococcosis is usually clinically. Most cases of pulmonary cryptococcal infection are discovered serendipitously, not because of organ specific signs or symptoms. Occasionally, however, pulmonary symptoms dominate the clinical presentation and progression to respiratory failure and death are not unknown. However, among those HIV-infected patients with cryptococcal disease and without CHS involvement, fully two thirds had cough and shortness of breath. In contrast only 18% of those patients with culture-proven CNS disease had respiratory symptoms. These numbers add weight to the argument that all patients with CNS involvement have or have had antecedent pulmonary infection. Blood-borne spread to any organ, but the organism has a predilection for the CNS. It causes a granulomatous meningitis with or without clinically evident pulmonary or disseminated infection. In addition, there may be small cysts in the cerebral cortex. The clinical presentation is usually with headache, fever, and constitutional upset; neck stiffness, photophobia and focal neurologic signs are present.
Skin disease is an extremely common complication of HIV infection, affecting up to 90% of persons. Some of the skin conditions also are commonly seen in uninfected persons (e.g. seborrheic dermatitis) but are of increased severity in the HIV infected person. Other skin diseases are relatively unique to HIV infection (Kaposi’s sarcoma)(Fig. 8).
Fig.8. Elements of Kaposi’s sarcoma
The average HIV infected patient has at least two and often more different skin conditions simultaneously. It is useful to classify the cutaneous disorder seen with HIV disease as either infectious disorder, hypersensitivity disorders and drug reactions, or neoplasms.
Oral lesions (Fig. 9) have been recognized as prominent features of HIV infection since the beginning of the epidemic. Some of these changes are reflections of reduced immune function manifested as oral opportunistic conditions, which are often the earliest clinical features of HIV infection. Some, in the presence of known HIV infection are highly predictive of the ultimate development of the full syndrome, whereas others represent the oral features of AIDS itself.
Fig.9. Oral lesions in AIDS
They include oral infections in patients with primary immunodeficiency, leukemia, and diabetes, and those resulting from radiation therapy, cancer chemotherapy and bone marrow supression. In the prospective cohorts of HIV infected homosexual and bisexual men hairy leukoplakia pseudomembranous candidiasis are the most common oral lesions.
Fig.10. Oral Kaposi’s sarcoma in AIDS
Kaposi’s sarcoma (KS) in patients with AIDS produces oral lesions in many cases (Fig. 10).
The lesions occur as red or purple macules, papules, or nodules. Occasionally the lesions are the same color as the adjoining normal mucosa. Although frequently asymptomatic, pain may occur because of traumatic ulcerisation with inflammation and infection. Bulky lessions may be visible or may interfere with speech and mastication. Diagnosis involves biopsy. Lesions at the gingival margin frequently become inflamed and painful because of plaque accumulation.
From the outset of the HIV epidemic, clinicians everywhere noted a high prevalence of the gastrointestinal (GI) signs and symptoms. Some of these manifestation such as weight loss, dysphagia, anorexia, and diarrhoea are almost universally among patients with HIV. Early and complete invasive and noninvasive evulation of these patients should be undertaken with particular attention to treatable non-HIV-associated biliary tract disease. Hepatic parenchymal disease likewise is common in patient with HIV infection.
Cramping paraumbilical abdominal pain, weight loss (Fig. 11, 12) and large-volume diarrhea are common in patient with HIV disease.
Fig.11. Loss of weight in AIDS
Fig.12. Loss of weight in AIDS
The majority of HIV patients with these complaints has specific small bowel infection. Certainly routine colonic bacterial pathogens such us Salmonella, Shigella and Campylobacter, which may be persistent and mimic chronic inflammatory bowel disease, should be excluded by the adequate culture techniques. Likewise, routine and atypical parasitic infestation including that caused by Giardia lamblia, E. histolytica, Criptosporidium and I. belli must be excluded. Colonic diarrhea usually is associated with frequent small volume stools, left lower quadrant or suprapubic cramping, rectal urgency (tenesmus), and proctalgia and dyskenesia (painful defecation). On occasion a small amount of bright red blood may be noted. Once again, in the majority of these patient with diarrhea of colonic origin, specific bacterial and parasitic pathogens can and should be easily isolated by careful analysis of the stool. In addition some patient may have classic herpetic perianal ulceration which can be diagnosed by specific viral culture of swabs taken directly from the perianal area. CMV proctocolitis has been described as having sigmoidoscopic features suggestive of focal ishemic colitis that is submucosal hemorrhages and discrete shallow ulceration of distal colonic mucosa. Once again, obtaining specific biopsy specimens for histology and viral culture is indicated. Even in the absence of focal or diffuse colonic mucosal changes, biopsy specimens should be taken for histologic evaluation to look for the occasional patient with Cryptosporidium whose stools have beeegative for this organism.
On occasion, patients with HIV may suddenly develop ascites. Since some HIV-infected patient may have underlying cirrhosis (caused by either alcohol consumption or viral hepatitis), a sizeable percentage of them will have transudative ascites related to their chronic liver disease. Careful evaluation of the ascites fluid, including performing cytology, and acid-fast stains should be done early to exclude patients with malignancy and tuberculosis peritonitis.
Malignancies as a complication of immunodeficiency have been well described in the literature, being recognized long before the advent of the HIV epidemic. The incidence of both Kaposi’s sarcoma (KS) and non-Hodgkin’s lymphoma (NHL) are marked by increased in immunosuppressed allograft recipients. It is therefore not suprising that patients with HIV infection, who also have proformed defects in cell-mediated immunity also develop these two malignancies. KS once a rarely reported malignancy is the most commoeoplasm affecting HIV-infected individuals. IT is seen primarily in homosexual men and has only rarely been reported in intravenous drug users or other risk groups. The pathogenesis of KS and HIV-infected patients remain uncertain. The natural history of KS associated with HIV infection more closely resembles that observed in immunosuppressed allograft patients. The disease tends to progress with time and is associated with the appearance of larger and more numerous cutaneous lesions (Fig. 13).
Fig.13. Cutaneous lesions in AIDS
However, the course of the disease is unpredictable. A patient may have relatively few lesions that remain stable over time. New cutaneous lesions may not appear for many months but may be followed by a sudden and rapid increase in disease activity. Visceral involvement with KS is extremely common and can involve almost any visceral site. Careful endoscopic examination will reveal gastrointestinal sites of disease in most patient. Athough KS is usually not a direct cause of death in HIV-infected, the morbidity associated with more advanced disease with more advanced disease can be significient.
Cutaneous lesions may become painful and if large cutaneous surfaces are involved can restrict movement. Lymphatic obstruction is common and can result in severe edema, most commonly involving the extremities or the face. visceral spread of KS is rarely symptomatic, particularly when it involves the gastrointestinal tract. Careful examination of the skin and oral cavity at each clinic visit is the key to early diagnosis. Once lesions are identified, histologic confirmation should be obtained.
The non Hodgkin’s lymphomas are a heterogenous group of malignancies. Their biologic behavior ranges from indolent requiring no therapy, to aggressive malignancies with few long-term survivors. In the most commonly used classification system for the NHL, these malignancies are divided into three major categories: low grade, intermediate grade, and high grade, according to pathologic characteristics of involved lymph nodes and morphologic criteria of the lymphoma cells.
Infection with the HIV is associated with a wide spectrum of hematologic abnormalities. These abnormalities are found in all stages of HIV disease and involve the bone marrow, cellular elements of the peripheral blood and coagulation pathways. The cause of these abnormalities is multifactorial. A direct suppressive effect of HIV infection, ineffective hematopoiesis, infiltrative disease of the bone marrow, nutritional deficiencies, peripheral consumption secondary to splenomegaly or immune dysregulation, and drug effect all contribute to the variety of hematologic findings in these patients. Many of these abnormalities are clinically significant, whereas others are more of academic interest.
Peripheral cytopenias are common in HIV-infected individuals and are due to either decreased production in the bone marrow or accelerated destruction in the peripheral circulation. In general the cytopenias increase in frequency as HIV-disease progresses. Anemia is the most common hematologic abnormality noted in patients with HIV disease. The largest HIV infection affects the lymphocyte, neutrophil and macrophage monocyte cell lines. Despite the hyperhammahlobulinemia noted in these patient, they suffer complications from both defective cellular immunity and dysregulated humoral immunity. The hallmark of HIV infection is progressive depletion of the CD-4 lymphocytes. This decrement presumably occurs through direct viral invasion of these cells. Early in HIV infection an initial increase in the CD-4 population occurs before a decline in the number of CD-4 cells is noted. Granulocytopenia independent of drug use is noted in approximately 50% of patients with HIV. Drug-induced neuthropenia is in the HIV-infected individual. Medication used to treat infection such as P. carinii pneumonia, toxoplasmosis and cytomegalovirus retinitis or colitis cause neuthropenia. Similarly, ridovudine is implicated as a cause of neuthropenia, ofteecessitating dose reduction or cessation of therapy. As for the complication of neuthropenia, most documented infection involve gram-negative organisms. The most common platelet abnormality found in HIV-infected patients is thrombocytopenia have only minor submucosal bleeding. characterized by petechiae, echymoses and occasional epistaxis. Rare patients have gastrointestinal blood loss. Laboratory findings reveal that patients generally have isolated thrombocytopenia, which usually is not accompanied by anemia and leukopenia. Patients with HIV infection, including those being treated with antibodies for an AIDS-opportunistic infection and those being treated with cytotoxic chemotherapeutic agents for HIV-related malignancies, may also develop thrombocytopenia secondary to a therapeutic intervention. In these patients severe thrombocytopenia should be managed as it is in the non-HIV-infected individual. Medications causing thrombocytopenia should be discontinued and platelet transfusion should be administered when indicated.
Diagnostics
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The first test developed to detected HIV infection was isolation of the virus through tissue culture. Unfortunately although sensitive for viral isolation the tissue culture procedure is expensive, time consuming and labor intensive. As a result soon after the initial discovery of HIV several tests were developed using protein products of the newly discovered virus to detect antibodies produced by the infected host. The two antibodi tests used most commonly are the enzyme-linked immunosorbent assay (ELISA) and the western blot. In addition to being less expensive, faster and easier to perform than viral culture, the ELISA and the Western blot test do not require working with like virus and therefore are safer. Over the best some years several novel techniques have been developed. The radioimmunoprecipitation assay (RIPA) is a more time consuming, and labor intensive test the Western blot, yet it provides much finer resolution of the high-molecular-weight envelope proteins than the western blot test. The RIPA is considered more sensitive and specific than the Western blot test, however, the time, expense, and need for active cell lines and radioactive materials make the RIPA a poor choice for routine testing in commercial laboratories. Rather its use is best reserved for difficult-to-diagnose cases. Like the RIPA the indirect immunofluorescence assay (IFA) requires preparation of HIV antigens that are expressed on infected cells and are stained subsequently. Infected cells are placed on the glass slides in a fixed monolayer and are incubated with patient serum. Anti-HIV antibodies present within the serum bind to antigens expressed on the surface of cells, and these bound antibodies are then detected with anti-human antibody that has been labeled with fluorescein isothiocyanate an ultraviolet-activated dye compound. after appropriate processing, the slide is viewed under a fluorescent microscope and the number of cells the intensity of staining and the staining pattern are assessed. Polymerase chain reaction (PCR) technique, introduced in the late 1980s, represent a major advance in the diagnosis of many disorders, including HIV infection. This powerful technique can amplify DNA existing in very small quantities through a series of binary replicative cycles. The PCR procedure can also be applied to RNA.
The pool of human lymphocytes possesses specific glycoproteins of their surface that play an important role in the cells activity and function CD-4 positive lymphocytes are the primary target of HIV infection, and the CD-4 receptor is the primary binding site of HIV. Throughout the course of chronic HIV infection the number of CD-4 lymphocytes is depleted and the loss of these cells is associated with development of the characteristic opportunistic infection and malignancies of AIDS. Thus the measurement of CD-4 positive lymphocytes is one of the most impotent determinates for clinically staging the disease status of HIV infected patients. In uninfected controls normal values for the CD-4/CD-8 ratio are 2.0 to 1.0. Normal values for CD-4 counts are generally 500 to 1000 cells/ml3 in adults.
Treatment
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Basic therapy consists of indication of antiviral agents. Use preparations, that inhibit the return transcriptasa of the virus: Azydotymidin (АzТ), Didanosin (ddi), Zalcytobyn (ddc), Stavodin (d4T), Lamivudin , Abacavir (АВС), Nevirapapin (NVP).
Till now monotherapy AZT (Retrovir, Zidovudin) was used. The preparation are prescribed (P.O.) 0,2 gr. 3 times per day constantly or courses, duration is not less than 3 months. Treatment will be carried out under the control of the general analysis of a blood with 2 times per one month during the first 2 months and subsequently once per month. In a stage preAIDS (secondary diseases) AZT is necessary to indicate till disappearance of a clinical symptomatology. If the clinical picture is not better Zidovidin is indicated only for that patient in which blood concentration are less than 500 cells in 1 mkl. With such treatment it is possible to prolong patients life, the number of resistant viruses to a preparation however is marked. So, monotherapy AZT is recommended only for prophylaxis of infection of fetus from mother.
Among new means with other mechanism of action use a specific inhibitor of proteases Krixivan, which is effective concerning resistant to AZT populations of a virus 0,8 g every 8 h. Preparations of a choice may be Rotonavir, Nelfinavir, Sacvinar-SGC, Amprenavir.
Recently it is proved, that efficiency of treatment essentially can be increased using a combination of two or three antiviral preparations. Therefore monotherapy was changed for polytherapy. The most frequently combination of two inhibitors of virus return transcriptasa (stavudin + didanosin, stavudin + lamivudin, zidovudin+didanosin, zidovudin + lamivudin, zidovudin+abacavir) and one inhibitor of a protease is used. At patients with high risk of disease progress (viraemia over 1 000 000 copies / ml.), and also in urgent cases use the two inhibitors of proteases and 1 -2 inhibitors of virus return transcriptasa.
Efficiency of specific treatment is controlled by monitoring with following criteria: 1) level HIV RNA in plasma; 2) quantity of T-lymphocytes CD4; 3) a clinical condition of the patient; 4) morphology and biochemistry of a blood (for detection of undersirable effects of an organism). Level HIV RNA in plasma is researched after 4-8 and 12-16 weeks from the beginning of treatment and subsequently each 3-4 months. The major condition of successful antiretrovirus therapy is its usage during all life of the patient, however it is interfered by a high toxicity of preparations and the complications connected with them. Complete treatment of patients with AIDS remains an unsolved problem. Last combination is considered the most effective, but also it does not cure patients with AIDS.
It is not less important preventive treatment of secondary diseases at AIDS. Against pneumocystic pneumonias the basic agent is Bactrimum. For initial prophylaxis of this disease Bactrimum is indicated 1 tablet duaring 3 days each week. At occurrence of pneumonia daily reception of preparation is prescribed. In case of an intolerance of Bactrim it is possible to indicate Dapsone or Primachin in a combination with Clindamicin. At presence of herpetic infections indicate Acyclovir.
Against criptococus and other funguses use Amphotericinum, against bacteria – the appropriate antibiotic. At sarcoma Kaposhi freezing elements of an eruption by liquid nitrogen, irradiation, chemotherapy are indicated. The immunotherapy of AIDS is at developing stage.
Viral hepatitis
Diagnosis
Preliminary diagnosis of viral hepatitis is based on epidemiological anamnesis, finding of the development of the disease, clinical picture with account of peculiarities of the ways of the transmission, duration of incubation period, presence of prejaundice period, presence of typical subjective and objective signs with account of the patients age.
Diagnosis is confirmed by routine and specific laboratory tests. In routine blood test of the patients with viral hepatitis lymphocytosis is observed with moderately expressed course and in serious course of the disease – anemia and leucopenia. ESR is slightly decreased. In urine urobilin and bile pigments are observed. During climax period, particularly during medium serious and serious forms, there are no stercobilin in stool.
Increased content of general bilirubin, primarily on account of its direct fraction is observed in blood serum during all jaundice period. Ratio of direct and indirect fraction composes 3:1. In all patients already in pre-jaundice period of the disease, during all jaundice period and in the period of early reconvalescence increased activity of ALT, AST is observed, testifying about the presence of cytolytic processes in liver.
Specific antigens (HBsAg) and antibodies to antigens of all known at present time viruses of hepatitis are revealed in the blood of patients with help of these methods. Discovery of antibodies of class of IgM testifies about acute disease. Discovery of other classes of immunoglobulins antibodies testifies about lingering or chronic course of viral hepatitis or about earlier infectious process or about disease in the past.
Differential diagnosis
Differential diagnosis of viral hepatitis is necessary to perform with diseases like leptospirosis, yersiniosis, mononucleosis, malaria, mechanic and hemolytic jaundice, toxic hepatoses.
Leptospirosis is characterized by acute beginning of the disease, often with chill, continuation of fever during of climax of the disease and jaundice, pain in muscles, especially in calfs, hemorrhagic syndrome. In blood leucocytosis with neuthrophillosis and shift in the formula to the left, accelerated ESR are observed. Activity of ALT and AST is moderately raised or normal relation of direct and indirect bilirubin 1:1. In blood serum concentration of urea and residual nitrogen increases. Stool is colored. In urine erythrocytes, leukocytes, like wax cylinders are marked in large quantity. Diuresis decreased till anuria.
In generalized forms of yersiniosis jaundice may be also observed, however it is accompanied by fever, metastatic focuses in other organs and tissues, leucocytosis with nuetrophilosis, accelerated ESR, aggravations and relapses. Diagnosis is confirmed by serological methods with specific yersiniotic antigen.
In malaria there are clear alternation of attacks fever with chills, replaced by heat and sweat and periods of apyrexia. Often painful, increased in size spleen is marked. In blood hemolytic anemia, in fat drop blood and smear different forms of malarial plasmodia are reveled. In blood serum indirect fraction of bilirubin predominates.
In mechanic jaundice stones in gall bladder and bile passages, enlargement of head of pancreas and other signs are revealed with help of ultrasound investigation. In majority of the patients moderate increase of activity of ALT, AST, leukocytosis, accelerated ESR are marked. Hemolitic jaundice is characterized by anemia, accelerated ESR, increase of indirect fraction of bilirubin. Stercobilin is always present in stool.
Differential diagnosis of VH with hepatoses is complicated and demands from doctor thoughtful and painstaking work. During this essential significance possesses correctly taken anamnesis.
Outcomes of the disease
Viral hepatitis most often ends with complete reconvalescence. In some patients may be cholecystitis, cholangitis, pancreatitis, dyskinesia of bile excreting pathways after an acute hepatitis. In 5-10 % of patients lingering course with periodical aggravations, caused by prolonged persistence of virus is observed. In such cases chronic hepatitis develops. This variant of the course of the disease is typical of viral hepatitis B and C chronic hepatitis may end up by liver cirrhosis.
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Treatment
Treatment is used complex and depends on the clinical form and gravity of disease current. At mild current of a viral hepatitis in the acute period it is possible to prescribe only semi-bed regime, diet № 5, polyvitamines and desensitizing preparations: calcium gluconate, Diazolin, Diprazin or Tavegil. In case of meteorism, feeling of gravity in epigastrium area after the meal, unstable feces – Festal, Pancurmen, Allochol, Cholenzym are indicated.
At medioserious and serious current of the acute form of hepatitis a bed regime is provided together with the specific treatment. Desintoxication therapy consists of plentiful drink; 5 % solution of glucose, saline solutions, Ringer’s solution, Trisault, Quartasault, 20 % solution of Sorbit (or. Sorbitoli), donor Albumin (given in vein), one of enterosorbents SKN of different brands, carbaphosfer, Carbosilan, Sillard P, Enterosgel, Polyphepan. The quantity of drunk liquid should be balanced with a daily urine. Polarizing admixture: 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 improving metabolism in hepatocytes: Ascorbinic acid, Thiamin chlorid, Pyridoxine hydrochloride, cocarboxylase, Potassy Orotat, Riboxin, Citochrom C, Lipamid, Calcy Pangamat. Last two preparations are indicated mainly at accompanying hepatoses with fatty infiltration of liver (alcoholism, diabetes, thyrotoxicosis, an obesity etc.). For acidosis decreasing 2 % solution of sodium of a hydrocarbonate 25-50 mL (P.R.) 3-4 times per day or on 150-200 mL (I.V.) should be infused.
Among etiotropic agents moderate medical effect at acute virus hepatitis has human recombinative α-2-interferon – Reaferone, Intron A, Realdironi or analogue Laferone in powder, in amp. 1 000 000 IUN: from 1-st to 5-10-th day of the icteric period. Next days their efficiency falls. At acute hepatitis B Laferon is infused 1 000 000 IUN 2 times per day during 5-6 days, then 1 000 000 IUN 1 time per day during 5 days. If medical effect is insufficient, there should be continued infusing 1 million UN 2 times per week during 2 weeks. It is worthy to use Leicinferone as the basic component which is the admixture of natural α-interferons of donor leucocytes, the factor of necrosis of tumours and Interleicin-1. However many clinicians challenge expediency of indication of interferon at the hepatitis of acute period. More physiologic is the stimulation of endogenic interferonogenesis with the help of such inductores, as Mefanam acid, Prodigiosan, Pyrogenal, Nifluril, Cycloferon.
At threat of hepatonecrosis – glucocorticoids 150-200 mg are prescribed. The dose of prednisolon per day, must be reduced after the patient gets out of extremely serious condition. The volume of infusion solutions is enlarged up to 30-50 mL/kg per day. Ornithin (ornicetyl) promotes a linkage and removing out of organism nitrous bonds and improves a metabolism.
A lactulose reduces an adsorption of ammonia from intestine in blood, especially in combination with Neomycin. With the aim of oppression of processes of an autolysis there should be used inhibitors of proteolytic enzymes Contrical or Gordox each 8 hours (I.V.) intravenous dropping, at improvement of a condition synthetic inhibitors. At retention of liquid in organism it is required to use Spironolacton (Veroshpiron), Kaliumsaving diuretics, or saluretics-Furosemid, Etacrinic acid. Psychomotor exaltation is stopped by Sody hydroxybutyrate in combination with Sibazon (Seduxen), Haloperidol. At increasing of hepatic failure there are used antilymphocytic gamaglobulin during 1-5 days with the control of quantity of lymphocytes in a pereferic blood, apparatus methods of clearing of patients blood, hyperbaric oxygenation.
At cholestatic form of a virus hepatitis the are effective preparations which form complexes inside intestine with cholic acids which caot be soaked up, cholestiramin and Bilignin. Fenobarbital is used which is the inductor of synthesis of Glucouroniltransferas. This enzym is necessary for conjugation of bilirubin with glucuronic acid, and stimulating its egestion with bile. Fenobarbital is indicated with combination of Cyanocobalamin. Simultaneously for intensifying secretion of bile Nospan and Cholenzym are indicated. After the termination of an acholia duodenal tubages 5-10 % solution of magnesy sulfat (1/4-1/2 glasses), Sorbit or Xilit (20 gr on 100 mL of hot water) 1 hour before breakfast are applied.
Bioflavonoids – Convaflavin, Carsili, Legalone, Silibor, Quercetin are indicated in case of the alonged reconvalescence. At hyperaminotransferasaemia – Aevit or Tocopherol acetas, Thymalin, T-activin, Dipiridamol (Curantyl), Isoprinosin (has also antiviral property) – give positive effects. There are used also Saparal, Methyluracil (or. Methacil), Natry nucleinic, Thymalin in a combination with Dipiridamol, Hofitol.
Cholagogue agents – broths of flowers of immortele, hips, thyme, mints peppery at the rate of 1 dining spoon of a herb or a mixture to 1 glass of water are indicated for convalescents Fenobarbital with Cyanocobalamin are applied during 10 days in case of hyperbilirubinemia with prevalence of untied fraction of pigment; preparations of choice can be Cordiamin or Sibazone (Seduxen) which also stimulate glucoruniltransferase of hepatocytes. At hyperbilirubinemia mainly at the expence of connected fraction stimulate a bile secretion using oxygen cocktails with cholagogue herbs and honey. Vitohepat or Cobamamid stimulate neogenesis and hemopoes, accelerate regenerative processes in liver, course of treatment lasts 15-20 days. At astenia and hypoproteinemia, and also for elimination of catabolitic influences of glucocorticoids which were used at the acute period, anabolic hormones: such as methandrostenolon (Nerobol), Phenobolin (Nerobolil) or Retabolil are indicated. For elimination of the asthenic phenomena, there are used Novopasit, tinctura of Valeriana root (20 gm: 200 mL), herbs of neetle, Thyme, Bromidums, and in rather serious cases – Chlozepid (or. Eleny), Sibazon (or. Seduxen), Relany, Barbiturates.
At the dyspeptic phenomena caused by oppression of secretory function of digestion organs, also Allochol, Liobily, Cholenzym, Festal, Panzynorm forte, Pancurmen, Pancreatin, Pancitratit, Vobensym are widely used.
At posthepatitic hepatomegalias without signs of cytolisis it is not reasonable to indicate Lydase – promoting a resorption of a fibrous tissue, 10 injections every 2-nd day. It can be infused only after exception of inflammatory process in hepatobiliar ways (will carry out control duodenal intubation).
Chemotherapeutic preparations are indicated in case of the bacterial cholecystitis. At mild current of disease it is possible to use only a fortnight course of Nicodin, at appreciable changes antibiotics or Nitrofurans preparations are indicated.
It is possible to make antibioticosensetivity of microorganisms allocated from bile. For definition there are used mediums, which content bile of the patient as it influences on essentially activity of antibiotics. Use Ampicillin, Carbenicilin Dinatry salt, Erythromicin, Cefazolin, Furazolidone, Furagin, at Candida infection sody salt of Levorin. Chemiopreparations indicate in average therapeutic doses during 7 – 8 days.
Specific therapy of chronic virus hepatitises is carried out by preparations of α-interferon (Intron A, Roferon, Realdiron, Reaferon, Laferon). They are effective in case of low replicative activity of the virus determined in blood virus DNA (HBeAg) at a hepatitis B and virus RNA at hepatitis C. The additional indication is high activity of serum Alanineaminotransferase. One of the specified preparations inject (I.M.) or subcuteneous 3 – 5 million IUN per day 3 times per week during 6 months. Treatment should be stopped, if positive results were not observed after 3 months. The positive effect is observed at 40-50 % of patients with hepatit B and at 20-30 % of patients with hepatit C. At chronic hepatit D less than 10 % of patients are released from viruses even if treatment lasts 1 year. In some cases the success of immunotherapy of virus hepatitises may be increased if preliminary indicate short course of treatment about 6 weeks of glucocorticoids. Combined usage of interferon and Thymalin, Essentiale, Lamivudin, Chenodesoxycholyc acids has been proved.
The side-effects of α-interferon are noticed at half patients right after injection, among them are headache, fever, myalgia, arthralgia, general delicacy. They can be prevented by means of analgetics. Among the remote side-effects are: nausea, diarrhea, depression, irritability, leuco- and thrombocytopenia. Decreasing of a dose of preparation allows to weak these disorders. There are serious complications (sepsis, psychosis, autoimmune diseases), that demand an immediate cancellation of interferonotherapy.
At chronic hepatitis B in a phase of replication there are applied a peroral preparation Lamivudin (Zeffix). It provides the same level of seroconversion, as standard course of treatment by interferon.
At chronic hepatitis with low replicative activity of a virus preference is given to pathogenetic agents improving metabolic and reparative processes in liver, such as: Silibor, Carsil, Liv-52, Hepatofalk, Planta, Hepabenne, Antral, Tocopherol Acetat etc.
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Prophylaxis
If the patient is hospitalized, he should be placed in a private room with separate toilet facilities. The major reason for such isolation is to prevent the spread of type A hepatitis. Even with lax precautions, such spread is very rare; most patients with type A hepatitis are no longer excreting virus once they have become symptomatic. Nevertheless, there are exceptions, and isolation is prudent. Secretions and blood products should be handled with care gowns, masks, and gloves are not necessary, but a prominent sign reading “needle and blood precautions” is appropriate. Labeling of blood specimens from a patient with hepatitis, is a common practice. It should be stressed, however, that all blood from any patient should be handled as if potentially infectious.
If the patient with viral hepatitis is at home, the patient should be advised about care in personal hygiene – careful hand washing. Attention also should be paid to blood and blood products and the handling of cuts and lacerations.
Recommendations regarding the prevention of acute hepatitis are governed by the type of viral hepatitis that is being considered. In the case of acute type A hepatitis, all family members, and close personal contacts should receive immune serum globulin (ISG) at a dosage of 2-5 mL in as soon as possible after exposure. Office, factory, and school contacts do not need to be treated. Immune serum globulin can be given for up to 4 weeks after exposure, but it probably is only effective if given within 7-14 days.
In the case of acute type В hepatitis, prophylaxis only needs to be provided for “regular” sexual contacts. The best form of protection is argued Hepatitis В immune globulin (HBIG) at a dosage of 5 mL in as soon as possible and again 1 month later has been the conventional recommendation in this situation. However, the efficacy of HBIG in preventing the sexual spread of acute type В hepatitis has not been well proved. In addition, there is now evidence that postexposure immunization with HBV vaccine, can attentuate or prevent acute type В hepatitis. Vaccine should be given as soon as possible and then 1 month and 6 months later.
