Both the enterically transmitted forms of viral hepatitis, hepatitis A and E, are self-limited and do not cause chronic hepatitis (rare reports notwithstanding in which acute hepatitis A serves as a trigger for the onset of autoimmune hepatitis in genetically susceptible patients or in which hepatitis E (Chap. 332) can cause chronic liver disease in immunosuppressed hosts, for example, after liver transplantation). In contrast, the entire clinicopathologic spectrum of chronic hepatitis occurs in patients with chronic viral hepatitis B and C as well as in patients with chronic hepatitis D superimposed on chronic hepatitis B.
CHRONIC HEPATITIS B PATHOPHYSIOLOGY
The likelihood of chronicity after acute hepatitis B varies as a function of age. Infection at birth is associated with clinically silent acute infection but a 90% chance of chronic infection, whereas infection in young adulthood in immunocompetent persons is typically associated with clinically apparent acute hepatitis but a risk of chronicity of only ~1%. Most cases of chronic hepatitis B among adults, however, occur in patients who never had a recognized episode of clinically apparent acute viral hepatitis. The degree of liver injury (grade) in patients with chronic hepatitis B is variable, ranging from none in inactive carriers to mild to moderate to severe. Among adults with chronic hepatitis B, histologic features are of prognostic importance. In one long-term study of patients with chronic hepatitis B, investigators found a 5-year survival rate of 97% for patients with mild chronic hepatitis, 86% for patients with moderate to severe chronic hepatitis, and only 55% for patients with chronic hepatitis and postnecrotic cirrhosis. The 15-year survival in these cohorts was 77%, 66%, and 40%, respectively. On the other hand, more recent observations do not allow us to be so sanguine about the prognosis in patients with mild chronic hepatitis; among such patients followed for 1−13 years, progression to more severe chronic hepatitis and cirrhosis has been observed in more than a quarter of cases.
More important to consider than histology alone in patients with chronic hepatitis B is the degree of hepatitis B virus (HBV) replication. As reviewed in Chap. 332, chronic HBV infection can occur in the presence or absence of serum hepatitis B e antigen (HBeAg), and generally, for both HBeAg-reactive and HBeAg-negative chronic hepatitis B, the level of HBV DNA correlates with the level of liver injury and risk of progression. In HBeAg-reactive chronic hepatitis B, two phases have been recognized based on the relative level of HBV replication. The relatively replicative phase is characterized by the presence in the serum of HBeAg and HBV DNA levels well in excess of 103−104 IU/mL, sometimes exceeding 109 IU/mL; by the presence in the liver of detectable intrahepatocyte nucleocapsid antigens (primarily hepatitis B core antigen [HBcAg]); by high infectivity; and by accompanying liver injury. In contrast, the relatively nonreplicative phase is characterized by the ...