A clinicopathologic study in a total of 164 patients with acute hepatitis delta virus (HDV) infection showed that nine male patients (5.5%) had evidence of liver cirrhosis prior to or during the episode of acute hepatitis. All nine patients had typical clinical presentations and laboratory findings of acute viral hepatitis. Four of them had prolonged prothrombin time, three developed ascites and one finally died of hepatic failure. Clinical ascites occurred more frequently in cirrhotic patients with severe but non-fulminant hepatitis than their non-cirrhotic counterparts (p less than 0.05). In addition, histologic studies in five patients with cirrhosis disclosed diffuse lobular necrotizing inflammatory activity, with four showing bridging hepatic necrosis, which also occurs more frequently in cirrhotic than in non-cirrhotic patients (p less than 0.05). The data suggest that HBsAg positive patients with cirrhosis are susceptible to acute HDV infection which may lead to extensive necrosis or even decompensation and failure, simulating decompensation of the underlying liver disease. Therefore, careful clinicopathologic work-ups are required for accurate diagnosis and correct assessment of their outcomes.