VIROLOGY HEPATITIS VIRUSES Lec ( ) Dr.ESRA HASSAN

1. VIROLOGY HEPATITIS VIRUSES Lec ( ) Dr.ESRA HASSAN VIRAL hepatitis , is a systemic disease primarily involving the liver . CAUSES hepatitis A virus(HAV) infectious hepatitis hepatitis B virus (HBV) Hepatitis C virus HCV Hepatitis D virus HDV Hepatitis E virus HEV Hepatitis G virus HGV

2. OTHER VIRUSES ASSOCIATED WITH HEPATITIS (SPORADIC HEPATITIS ). • YELLOE FEVER VIRUS • CYTOMEGALO VIRUS CMV • HERPES SIMPLEX VIRUS • RUBELLA VIRUS • ENTEROVIRUSES • HEPATITIS VIRUSES , produce acute inflammation of liver ,resulting clinical illness characterized by fever ,GIT ,symptoms illness ( nausea ,vomiting and jaundice . • Identification histopathological lesions in liver during acute disease regardless of virus type .

4. HEPATITIS A VIRUS HAV • TYPICAL enterovirus ,picornavirus family . • SS-RNA ,non enveloped ,icosahedral NC ,replicate in cytoplasm . • Hepatovirus genus ( one serotype ) • Transmission ,feco-oral. • *human is reservoir of HAV . • Virus appears in feces roughly 2 weeks before the appearance of symptoms . • children are most frequently infected group . • -occur as outgreaks ,fecally contaminated food or water • -unlike HBV , HAV is rarely transmitted by the food ( level of viremia is low) . • -chronic infection dose not occur .

6. PATHOGENESIS • THE virus probably replicates in the GIT and spread to liver via the blood . • Hepatocyte is infected by the mechanism by which cell damage occurs is unclear . • HAV in culture cell produces no CPE • -IMMUNE RESPONSE , CONSIST INITIALLY OF IgM Ab detectable at the time jaundice appears ,it is diagnostic of HAV,3 WEEKS LATER ,PRODUCTION OF IgG Ab ( long life protection ) • CLINICAL FINDING • Typical manifestation of hepatitis ) • typical manifestation of hepatitis • most cases resolve spontaneously in 2-4 weeks . • -short incubation period 25 -30 days • Most HAV INFECTION are asymptomatic ,detected only by presence of IgG Abs .

7. LABORATORY DIAGNOSIS • IgM Ab is most important . • 4 fold rise in IgG TITER • -isolation of virus in cell culture is possible ( not available in diagnostic lab ,) • TREATMENT AND PREVENTION • Inactivated HAV ,is not yet available • -passive immunization ,immune serum globulin prior to infection or early in incubation period • -proper hygiene ,swege disposed ,hand washing

9. HEPATITIS B VIRUS HBV • -member of hepadnavirus family. • Envevirion ,icosahedral nuclic acid • Partially double strand circular DNA genome • Surface Ag HBsAgimportant for lab diagnosis • -with in the core ,DNA dependent RNA polymerase • E.M of patient serum contain 3 different particles • few 42 nm virion ( dane particle ) • 2- long filamentous 22 nm widw • Core antigen HBcAg • Core antigen (HBcAg) • 5-e Ag important indication of transmissibility . • HBs Ag has agroup specific Ag , ( a ) and 2 sets of mutally exclusive epitope ,d or y and w or r , this leads to 4 serotype adw ,adr .awy ,ayr ( useful ) is epidemiology . • Human are only natural host

11. REPLICATIVE CYCLE • Enter ------uncoating DNA polymeras synthesis the missing portion of DNA ----Double stranded closed circular DNA is formed in the nucleus ,some of these DNA integrates into hepatocyte DNA and some serves as template for Mrna ,synthesis ,Mrna not only functions in protein synthesis but but also is the template for minus strand of progeny DNA . • MINUS STRAND THEN SERVES AS THE template for the positive strand of genome DNA ,this is similar to but different from the process in retrovirus , progeny HBV with it is HBs Ag containing envelope is released from cell membrane by budding .

12. MODE OF TRANSMISSION • 1-via blood ,needle stick injuries ( addicts , I .v drug abusers ) • Screening of blood for HBs Ag .has greatly decreased the number of transfusion associated cases of HBV . • 2- sexual transmission • 3- from mother to chiold during birth or breast feeding . • HBV is worldwide ,particularly prevalent in porient ,in that region incidence of hepatoma , HBV may be human tumer virus . • -immunization against HBV may reduce incidence of hepatoma.

16. PATHOGENESIS • Virus enters B ------virus infect hepatocutes causing necrosis and inflammation • immune attack ,against viral Ags on infected hepatocyte may play important role in pathogenesis • Ag-Ab complexes ,cause some of early symptoms such as arthralgias some of the complication of chronic hepatitis immune complex and vasculitis . • 10% of patients with HB become chronic carriers of HBV due to a persistent infection of the hepatocytes which results in the prolonged presence of HBV and HBsAg in the blood . • HBV DNA exist primarly as an episome in the cytoplasm of persistentely infected cells a small amount of HBV DNA is integrated in to cell DNA . • A high rate of hepatocellular carcinoma occurs in chronic carriers . • -life long immunity is mediated by humoral Ab against HBsAg .

17. CLINICAL FINDING • Many HBV infectious are asymptomatic. • With HBV symptoms tend to be more severe and life threatening hepatitis can occur • LAB DIAGNOSIS • Immunoassay for HBsAg ,HBsAg appears during incubation period ,detectable in most patients during prodrome and acute disease it falls to undetectable levels during convalescence in most case . • In prolonged presence indicates the carriers state and the risk of chronic hepatitis . • There is a period of several weeks when HBsaG HAS DISAPPEARED BUT hbS Ab is not yet detectable ( window phase ) at this time HBcAb is always positive and can be used to make the diagnosis . • The test for HBcAg is not readily available . • HBeAg arises during the incubation period ,present during prodrome and early acute disease . • It is presence is an important indicator of transmissibility .the presence of HBeAb indicated low transmissibility .

20. TREATMENT AND PREVENTION • Alpha interferon . for treatment of chronic HBV • Prevention ,use of vaccine or hyperimmune globulin or both . • Vaccine ,contain HBsAG PRODUCED in yeasts by genetic techniques . • INDICATIONS OF VACCINATION • People frequently exposed to blood or blood products such as health care personnel( medical students ,surgeons and dentists ) • Patient receiving multiple blood transfusions or dialysis . • Patient with frequent sexually transmitted disease • Abusers of illicit i.v . drugs • Hepatitis B immuneglobulin HBIG =high titer oh HBsAb .providimmrdiate protection passive to individual known to be exposed to HBsAg positive blood such as accidedental needle stick .

21. HEPATITIS C VIRUS • 8 most common cause of post transfusion hepatitis • HCV is enveloped ,SSRNA ,resemble yellow fever virus • -----flaviviridea • 8 different genotype • MODE OF TRANSMISSION • BLOOD • SEXUAL CONTACT • Clinically • Resemble HBV infectious as far as acute infection , chronic liver disease ,predisposition to HCC CHRONIC CARRIER STATE . • MOST CASES ARE SUBCLINICAL

22. Hepatitis d virus ( delta agent ) • Small dna genome ,defective virus can occur only in patient previously infected by hepatitis B virus can replicate only in HBV infected cell • Mode of transmission by blood . chronic carriers state can occur • HEPATITIS e virus HEV • MAJOR cause of enteric transmitted hepatitis • Common cause of water borne • Clinically resemble to HAV with exception of a high mortality rate in pregnany woman • Chronic liver disease not found • There is prolonged carrier state • HEPATITIS G VIRUS • Flavivirideae family • The significant of hgv infection in liver disease is not clear

23. Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCVThe infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis) which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including liver cancer[1] or life threatening esophageal varices and gastric varices. • The hepatitis C virus is spread by blood-to-blood contact. Most people have few, if any symptoms after the initial infection, yet the virus persists in the liver in about 85% of those infected. Persistent infection can be treated with medication, peginterferon and ribavirin being the standard-of-care therapy. 51% are cured overall. Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.

24. Signs and symptoms • Acute • Acute hepatitis C refers to the first 6 months after infection with HCV although symptoms may appear within a day if infection was caused by any method of intravenous injection. Between 60% and 70% of people infected develop no symptoms during the acute phase unless infection was caused by direct access to the blood stream as crossing the blood brain barrier is then made up to 100 times easier. Main symptoms consist of general cold and flu like symptoms with increased loss of senses. • The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and antibodies to the virus are generally detectable within three to 15 weeks

25. Signs and symptoms • Acute • Acute hepatitis C refers to the first 6 months after infection with HCV although symptoms may appear within a day if infection was caused by any method of intravenous injection. Between 60% and 70% of people infected develop no symptoms during the acute phase unless infection was caused by direct access to the blood stream as crossing the blood brain barrier is then made up to 100 times easier. Main symptoms consist of general cold and flu like symptoms with increased loss of senses. • The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and antibodies to the virus are generally detectable within three to 15 weeks

26. Chronic • Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic, and it is mostly discovered accidentally (e.g. usual checkup). • Generalized signs and symptoms associated with chronic hepatitis C include fatigue, flu-like symptoms, joint pains, itching, sleep disturbances, appetite changes, nausea, and depression. • Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension. Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen), bruising and bleeding tendency, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. Hepatic encephalopathy is due to the accumulation of ammonia and other substances normally cleared

27. Liver enzyme tests show variable elevation of ALT and AST. Periodically, they might show normal results. Usually prothrombin and albumin results are normal, but may become abnormal, once cirrhosis has developed. The levels of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies, such Virology • The hepatitis C virus is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus. It is the only known member of the hepacivirus genus in the family Flaviviridae. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.).

28. Liver enzyme tests show variable elevation of ALT and AST. Periodically, they might show normal results. Usually prothrombin and albumin results are normal, but may become abnormal, once cirrhosis has developed. The levels of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies, such Virology • The hepatitis C virus is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus. It is the only known member of the hepacivirus genus in the family Flaviviridae. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.).

29. The hepatitis C virus is transmitted by blood-to-blood contact. In developed countries, it is estimated that 90% of persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via injecting drug use or sexual exposure. In developing countries, the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood products. There has not been a documented transfusion-related case of hepatitis C in the United States for over a decade, as the blood supply is vigorously screened with both EIA and PCR technologies.

30. Transmission • Sexual activities and practices were initially identified as potential sources of exposure to the hepatitis C virus • Injection drug use • Blood products • Blood transfusion, blood products, or organ transplantation prior to implementation of HCV screening

31. Vertical Vertical transmission refers to the transmission of a communicable disease from an infected mother to her child during the birth process. Mother-to-child transmission of hepatitis C has been well described, but occurs relatively infrequentl

33. Treatment • The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 50% of these do not respond to therapy. There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5% to 0.74% per year).[34][35] However, the majority of patients with chronic hepatitis C will not clear it without treatment. • Medications (interferon and ribavirin)