Presumed Cryptogenic Liver Disease in Germany: High Prevalence of Autoantibody-Negative Autoimmune Hepatitis, Low Prevalence of NASH, No Evidence for Occult Viral Etiology

Abstract

Aim was to investigate possible underlying causes of presumed cryptogenic liver disease. A cohort of 126 consecutive patients with presumed cryptogenic hepatitis referred to a university hospital were reanalysed with respect to their clinical, laboratory and histological data. In 19 patients there was evidence for an exogenous-toxic liver damage. Diagnosis of non-alcoholic steatohepatitis could be established in 22 patients. Viral origin was excluded in all patients by serological and PCR-based assays for the known hepatitis viruses and the viruses GBV-C and SENV. Furthermore, transmission studies in non-human primates using acute phase plasma of patients with severe cryptogenic hepatitis revealed no episode of transmissible hepatitis, that could give a hint to so far unknown viruses as etiological agent. In all patients negative autoantibodies were recorded. Nevertheless, in 43 patients the diagnosis of definite or probable seronegative autoimmune hepatitis (AIH) could be assumed by the application of the International Autoimmune Hepatitis (IAH)-Score. Only 42 patients still remained with cryptogenic liver disease (CLD). Compared to patients with seronegative AIH patients with CLD were significantly older, had a longer duration of their disease, lower values of transaminases, more frequently a cholestatic liver enzyme pattern, a lower grade of inflammation in the liver and no response to immunosuppressive therapy. Only one third of patients with initially presumed cryptogenic liver disease remained cryptogenic, while another third of patients could be identified as seronegative autoimmune hepatitis by the IAH-Score with obvious benefit from immunosuppressive therapy.