Risk factors for development of lethal sequelae after hepatitis B virus infection in humans

Serious late sequelae including chronic active hepatitis, cirrhosis, massive necrosis, and hepatocellular carcinoma may develop in patients infected with hepatitis B virus. Clinical and epidemiologic risk factors for such complications have not been identified. To examine this question, the clinical and pathologic features of the 60 patients with documented hepatitis B virus infection who underwent postmortem examination at the Johns Hopkins Hospital were reviewed. In 27 patients (45 percent), the outcome of hepatitis B infection was nonlethal, i.e., at autopsy, the liver showed either no histopathologic lesions attributable to hepatitis B infection, acute viral hepatitis, or chronic persistent hepatitis. Lethal outcomes of hepatitis B infection, i.e., chronic active hepatitis, cirrhosis, hepatocellular carcinoma, and/or massive hepatic necrosis, were present in the remaining 33 (55 percent) patients. Chronic active hepatitis was observed more frequently in whites (p less than 0.05) and males (p less than 0.05). Lethal outcomes of hepatitis B infection were correlated with recent or concomitant exposure to known hepatotoxic agents (p less than 0.05), including heavy ethanol abuse, isoniazide, hydrocarbon exposure, methyldopa, and the chemotherapeutic agents busulfan and methotrexate. In addition, a lethal outcome of hepatitis B virus, particularly massive hepatic necrosis, was positively correlated with a history of nephrolithiasis (p less than 0.005). Recent, concomitant treatment with immunosuppressive agents, given in 24 patients (40 percent), was correlated with the absence of lethal sequelae (p less than 0.005). These data suggest that patients with recent exposure to hepatotoxic agents have an increased risk of lethal sequelae following hepatitis B infection. Furthermore, the results suggest that immunosuppressive or antiinflammatory therapy may be beneficial in reducing morbidity and mortality from hepatitis B virus infection.