Hepatitis B

1. Hepatitis B HBV is a Hepadna virus. An extremely resistant strain capable of withstanding extreme temperatures and humidity. It can survive when stored for 15 years at -20°C, for 24 months at -80°C, for 6 months at room temperatures, and for 7 days at 44°C.

2. Hepatitis B The hepatitis B virus is transmitted through contact with the blood and body fluids of someone who is infected. The same way as human immunodeficiency virus (HIV). Hepatitis B is nearly 100 times as infectious as HIV.

3. Hepatitis B • The proportion of the world's population currently infected with the virus is 3 to 6% but up to a third have been exposed. • Hepatitis B is one of a few known non-retroviral viruses which employ reverse transcription as a part of its replication process.

4. Four stages in the viral life cycle • The first stage is immune tolerance. The duration of this stage for healthy adults is approximately 2-4 weeks and represents the incubation period. For newborns, the duration of this period often is decades. • Active viral replication is known to continue despite little or no elevation in the aminotransferase levels and no symptoms of illness.

5. Four stages in the viral life cycle • In the second stage, an inflammatory reaction with a cytopathic effect occurs. HBeAg can be identified in the sera, and a decline of the levels of HBV DNA is seen. The duration of this stage for patients with acute infection is approximately 3-4 weeks (symptomatic period). For patients with chronic infection, 10 years or more may elapse before cirrhosis develops.

6. Four stages in the viral life cycle • In the third stage, the host can target the infected hepatocytes and the HBV Viral replication no longer occurs. HBeAb can be detected. The HBV DNA levels are lower or undetectable, and aminotransferase levels are within the reference range. In this stage, an integration of the viral genome into the host's hepatocyte genome takes place. HBsAg still is present.

7. Four stages in the viral life cycle • In the fourth stage, the virus cannot be detected and antibodies to various viral antigens have been produced. Different factors have been postulated to influence the evolution of these stages, including age, sex, immunosuppression, and co-infection with other viruses.

10. IncubationViral incubation ranges from 45-180 days.

11. ACUTE HEPATITIS • Approximately 70 percent of patients with acute hepatitis B have subclinical or anicteric hepatitis, while 30 percent develop icteric hepatitis. The disease may be more severe in patients coinfected with other hepatitis viruses or with underlying liver disease • Fulminant hepatic failure is unusual, occurring in approximately 0.1 to 0.5 percent of patients. Fulminant hepatitis B is believed to be due to massive immune-mediated lysis of infected hepatocytes. This explains why many patients with fulminant hepatitis B have no evidence of HBV replication at presentation

12. Laboratory testing during the acute phase reveals elevations in the concentration of alanine and aspartate aminotransferase levels (ALT and AST); values up to 1000 to 2000 IU/L are typically seen during the acute phase with ALT being higher than AST. • The serum bilirubin concentration may be normal in patients with anicteric hepatitis. • The prothrombin time is the best indicator of prognosis. In patients who recover, normalization of serum aminotransferases usually occurs within one to four months.

13. Persistent elevation of serum ALT for more than six months indicates progression to chronic hepatitis. • The rate of progression from acute to chronic hepatitis B is primarily determined by the age at infection. The rate is approximately 90 percent for perinatally acquired infection • 20 to 50 percent for infections between the age of one and five years. • Less than 5 percent for adult-acquired infection .

14. CHRONIC HEPATITIS • A history of acute hepatitis is elicited in only a small percentage of patients with chronic HBV infection. • Many patients with chronic hepatitis B are asymptomatic, while others have nonspecific symptoms such as fatigue. Some patients experience exacerbations of the infection which may be asymptomatic, mimic acute hepatitis, or manifest as hepatic failure.

15. Physical examination may be normal or there may be stigmata of chronic liver disease. Jaundice, splenomegaly, ascites, peripheral edema, and encephalopathy may be present in patients with decompensated cirrhosis. Laboratory tests may be normal, but most patients have mild to moderate elevation in serum AST and ALT. • During exacerbations, the serum ALT concentration may be as high as 50 times the upper limit of normal and alfa-fetoprotein (AFP) concentrations as high as 1000 ng/mL may be seen .

16. Compensated cirrhosis — 85 percent at five years • Decompensated cirrhosis — 55 to 70 percent at one year and 14 to 35 percent at five years • Among Chinese patients with chronic HBV infection, the life-time risk of a liver-related death has been estimated at 40 to 50 percent for men and 15 percent for women

17. The incubation period lasts one to four months. A serum sickness-like syndrome may develop during the prodromal period, followed by constitutional symptoms, anorexia, nausea, jaundice and right upper quadrant discomfort. • The symptoms and jaundice generally disappear after one to three months, but some patients have prolonged fatigue even after normalization of serum aminotransferase concentrations.

19. Lab Studies Acute hepatitis B • High levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), at a range of 1000-2000 IU/mL, is the hallmark of the disease, although values 100 times more than the upper limit of normal can be identified. Higher values are found in patients with icteric hepatitis. ALT levels usually are higher than AST levels. • Albumin levels can be slightly low, and serum iron levels may be elevated. In the preicteric period (ie, before the appearance of jaundice), leukopenia (ie, granulocytopenia) and lymphocytosis are the most common hematologic abnormalities.

20. Patients with severe hepatitis experience a prolongation of the prothrombin time. • Several viral markers can be identified in the serum and the liver. HBsAg and HBeAg (marker of infectivity) are the first markers that can be identified in the serum. HBcAb (IgM) follows. • For patients who recover, seroconversion to HBsAb and HBeAb is observed. Patients with persistent HBsAg for longer than 6 months develop chronic hepatitis.

21. Chronic inactive hepatitis B • Healthy carriers have normal AST and ALT levels, and the markers of infectivity (ie, HBeAg, HBV DNA) may be negative. • HBsAg, HBcAb of IgG type, and HBeAb also are present in the serum.

22. Chronic active hepatitis B • Patients have mild-to-moderate elevation of the aminotransferases (<5 times the upper limit of normal). The ALT levels usually are higher than the AST levels. Extremely high levels of ALT can be observed during exacerbation or reactivation of the disease and can be accompanied by impaired synthetic function of the liver (ie, decreased albumin levels, increased bilirubin levels, and prolonged prothrombin time). • HBV DNA levels are high during this phase. HBsAg and HBcAb of IgG or IgM type (in case of reactivation) are identified in the serum.

23. If the AST levels are higher than the ALT levels, the diagnosis of cirrhosis must be excluded. • Hyperglobulinemia is another finding, predominantly with an elevation of the IgG globulins. • Tissue-nonspecific antibodies, such as antismooth muscle antibodies (20-25%) or antinuclear antibodies (10-20%), can be identified. • Tissue-specific antibodies, such as antibodies against the thyroid gland (10-20%), also can be found. Mildly elevated levels of rheumatoid factor usually are present.

24. Cirrhosis • In early stages, findings of chronic viral hepatitis can be found. • Later on as the disease progresses, low albumin levels, hyperbilirubinemia, prolonged prothrombin time, low platelet count and white blood cell count, and AST levels higher than ALT levels can be identified.

25. Transmission • Hepatitis B is largely transmitted through exposure to bodily fluids containing the virus. This includes unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, vertical transmission from mother to child during childbirth, and so on. • Without intervention, a mother who is positive for the hepatitis B surface antigen confers a 20% risk of passing the infection to her offspring at the time of birth. • This risk is as high as 90% if the mother is also positive for the hepatitis B e antigen.

26. Transmission • Roughly 16-40% of unimmunized sexual partners of individuals with hepatitis B will be infected through sexual contact. • The risk of transmission is closely related to the rate of viral replication in the infected individual at the time of exposure.

27. Immunopathogenesis • During HBV infection the host immune response is responsible for both hepatocellular damage and viral clearance. • The adaptive immune response, particularly virus-specific cytotoxic T lymphocytes (CTLs), contributes to nearly all of the liver injury associated with HBV infection.

28. By killing infected cells and by producing antiviral cytokines capable of purging HBV from viable hepatocytes, CTLs also eliminate the virus. Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology and platelets may facilitate the accumulation of CTLs into the liver.