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

Serious ate 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 <0.05) and males (p <0.05). Lethal outcomes of hepatitis B infection were correlated with recent or concomitant exposure to known hepatotoxic agents (p <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 <0.005). Recent, concomitant treatment with immunosuppressive agents, given in 24 patients (40 percent), was correlated with the absence of lethal sequelae (p <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.