Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology

Background-The histopathological spectrum and role of hepatitis viruses in cases of hypertransaminasaemia of unknown aetiology have not been correctly analysed in a sufficiently large number of patients. Methods-We studied 1075 consecutive patients referred for liver biopsy beca use of elevation of alanine aminotransferase (ALT) levels for more than six months. From this population we selected those cases in whom the aetiology could not be defined from clinical, biochemical, and serological data obta ined before biopsy. In these patients liver biopsies were reviewed, and hep atitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA were assayed in se rum by polymerase chain reaction (PCR). Serum hepatitis G virus (HGV)-RNA w as determined by PCR in 74 patients. Results-Of 1075 patients studied, the cause of the increased serum ALT leve ls remained elusive after appropriate testing in 109 patients (10.1%). Live r biopsies from these patients showed non-specific changes in 32.7% of case s, non-alcoholic steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV-DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than in healthy blood donors (26.7% v 3.4%; p<0.0 01). HGV-RNA was found in only one patient. The proportion of cases with de tectable HBV-DNA or HCV-RNA was 14.3% in patients with non-specific changes or NASH, 30.7% in patients with chronic hepatitis, and 61.5% in patients w ith cirrhosis. Cirrhosis was found more frequently in patients with positiv e HBV-DNA and/or HCV-RNA in serum than in those who tested negatively (p=0. 005). Conclusions-In our series, patients in whom biochemical and serological dat a did not determine the aetiology of the disease represented 10% of all cas es referred for liver biopsy for persistent elevation of serum transaminase s. Approximately 50% of patients had chronic hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult viral infections were f ound in a high proportion of cases in the first group and in a low percenta ge of patients in the second.