Natural course of subjects with elevated liver enzymes and normal liver histology

Background & Aims: Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue not infrequently reveals normal histology. Long term follow-up of such patients has not been performed.

Methods: We identified a total 70 subjects from our LB database with elevated liver function tests (eLFT) and normal liver histology after a mean of 90.5 ± 52.3 (range 15 – 216) months by reassessment of medical history, physical examination, laboratory testing, ultrasound, transient elastography and LB if indicated.

Results: At follow-up examination, fifteen (7 males/8 females; 21.4%) subjects had normal LFT and no further evidence of liver disease. A subset of thirty-seven (29/8; 52.9%) subjects had persistently eLFT without evidence indicating progressive liver disease but the cause thereof remained unexplained also at the follow-up visit. Three (0/3; 4.3%) subjects had consumed excessive alcohol with indicators of alcoholic liver disease. Eleven subjects (4/7; 15.7%) had developed steatosis on ultrasound examination along with weight gain and/or biochemical features of the metabolic syndrome. Additionally, 2 female patients developed autoimmune hepatitis, 1 presented with primary biliary cirrhosis, another male was diagnosed with cholangiocellular carcinoma. Conclusion: In approximately 1 out of 5 subjects, eLFT may be an early indicator of subsequent liver disease missed on the index LB. Attention should be applied to autoimmune liver diseases in women. Additionally, eLFT may herald consecutive hepatic steatosis if accompanied by weight gain and components of the metabolic syndrome.