A 32-year-old male with anorexia and fatigue is found to have persistently elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. He is also positive for HBsAg. Which of the following best describes the mechanism of liver injury in this patient?

Question

A 32-year-old male with anorexia and fatigue is found to have persistently elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.  He is also positive for HBsAg.  Which of the following best describes the mechanism of liver injury in this patient?

Quizplus · Accepted Answer

Hepatitis B virus infection progresses through two phases: the proliferative phase and the integrative phase. In the proliferative phase, the entire virion and all related antigens of the episomal HBV DNA are present. On the hepatocyte cell surface, viral HBsAg and HBcAg are expressed in conjunction with the major histocompatibility complex (MHC) class I molecules. This expression serves to activate the cytotoxic CD8+ T lymphocytes, which respond by destroying the infected hepatocytes. Note that the virion itself does not have a cytopathic effect. In the integrative phase, the HBV DNA is incorporated into the host genome of those hepatocytes that survived the immune response. Infectivity ceases and liver damage tapers off when the antiviral antibodies appear and viral replication stops. The risk of hepatocellular carcinoma, however, remains elevated because of the HBV DNA that has been integrated into the host genome. (Choice A) Hepatitis B virus has no direct cytotoxic effect. (Choice B) Host antibody HBsAb neutralizes HBV infectivity by binding to the viral surface antigen HBsAg and preventing the antigen from interacting with hepatocyte receptors. Note that this neutralization occurs before the virus enters the hepatocyte, and therefore would not be associated with hepatocellular damage. (Choice C) Antigen-antibody complexes cause some of the early symptoms of hepatitis B virus infection (eg, arthralgias, arthritis, and urticaria) as well as some of the chronic complications (eg, immune complex glomerulonephritis, cryoglobulinemia, vasculitis). These complexes are not responsible for hepatocellular damage, however. (Choice D) The pathogenesis of autoimmune hepatitis (not hepatitis B infection) involves antigen mimicry with generation of self-antigen recognizing CD4+ T lymphocytes that damage hepatocytes. Educational Objective: Hepatitis B virus does not have a cytotoxic effect itself; however, the presence of viral HBsAg and HBcAg on the cell surface stimulate the host's cytotoxic CD8+ T lymphocytes to destroy infected hepatocytes.

A 32-Year-Old Male with Anorexia and Fatigue Is Found to Have