Cirrhosis of undefined pathogenesis: Absence of evidence for unknown viruses or autoimmune processes



To examine whether unknown viruses or autoimmune processes contribute to the development of cryptogenic liver disease, we studied 48 patients undergoing liver transplantation who had non-A, non-B cirrhosis; non-blood-borne cirrhosis of unknown etiology; or autoimmune cirrhosis. After the diagnosis of hepatitis C virus infection was established by the presence of viral antibodies or viral RNA, patients were reclassified into three groups: hepatitis C virus infection, autoimmune cirrhosis and cryptogenic cirrhosis. Explant histological appearance, incidence of posttransplant hepatitis and immunological features were compared in the three groups. Thirty-one percent of patients had neither hepatitis C virus infection nor classical autoimmune cirrhosis and were classified as having cryptogenic cirrhosis. Unlike histological appearance in hepatitis C virus infection but similar to that in autoimmune cirrhosis, explant histological appearance of cryptogenic cirrhosis showed inactive cirrhosis with little inflammation. After transplantation, histological hepatitis of the allograft was demonstrated in 44% of patients with hepatitis C infection but in no patient with autoimmune or cryptogenic cirrhosis. The autoimmune score, developed from clinical criteria associated with autoimmune liver disease, was significantly lower in cryptogenic cirrhosis and hepatitis C virus infection than in autoimmune cirrhosis. Autoantibodies–including antinuclear antibodies, smooth muscle antibodies and liver-kidney microsomal antibodies–were not commonly present in serum of patients with cryptogenic cirrhosis, whereas antibodies to soluble liver antigens were found with increased frequency in this entity. We conclude that in many patients with liver disease, no pathogenesis can be identified. The mild inflammation of the explant on histological study and the low incidence of posttransplant hepatitis in cryptogenic cirrhosis suggest that chronic active viral infection is unlikely to be implicated in the pathogenesis. Although the presence of antibodies to soluble liver antigens implies an immune component to the pathogenesis of this disease, low autoimmune score and infrequent presence of other autoantibodies suggest that cryptogenic cirrhosis is distinct from classical autoimmune liver disease. (HEPATOLOGY 1993;17:593–598.)