What did we learn from the Shanghai hepatitis A epidemic?

A major outbreak of hepatitis A (HAV), associated with consumption of raw clams, occurred in Shanghai, China in 1988. Over 300 000 cases were reported, of which 47 (0.015%) were fatal. An elevated mortality rate was observed in hepatitis B surface antigen (HBsAg)-positive patients (0.05%). The majority of these patients were also hepatitis B e antigen (HBeAg)-positive, indicating active liver disease and high viral replication rates. The increased mortality in hepatitis B virus (HBV)/HAV coinfected individuals is hypothesized to be the result of T-cell-mediated destruction of HBV-infected hepatocytes, enhanced by acute HAV infection. Following recovery from HAV there is an increase in HBV expression and activated cytotoxic cells and subsequent cytolysis. Patients with chronic HBV infection are clearly at considerable risk of severe disease and increased mortality in the event of HAV infection. The period of greatest risk is during the immunoeliminative phase of HBV infection, which generally occurs in early adulthood. With the prevalence of HBV approaching 10% in this group, there is a clear opportunity for benefit from vaccination.