title: Natural course of subjects with elevated liver tests and normal liver histology.
abstract: OBJECTIVE
  Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue occasionally 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 tests and normal liver histology after a mean of 90.5 ± 52.3 (range 15-216) months and conducted reassessment of medical history, physical examination, laboratory testing, ultrasound, transient elastography and LB if indicated.
  
  
  RESULTS
  At follow-up examination, 15 (7 females (f)/8 males (m); 21.4%) subjects had normal liver tests and no further evidence of liver disease. A subset of 37 (29 f/8 m; 52.9%) subjects had persistently elevated liver tests without evidence indicating progressive liver disease but the cause thereof remained unexplained also at the follow-up visit. Three (0 f/3 m; 4.3%) subjects had consumed excessive alcohol with indicators of alcoholic liver disease. Eleven subjects (4 f/7 m; 15.7%) had developed steatosis on ultrasound examination along with weight gain and/or biochemical features of the metabolic syndrome. In addition, three (2 f/1 m) patients developed autoimmune hepatitis, one female presented with primary biliary cirrhosis. One male was diagnosed with cholangiocellular carcinoma 3 months after the initial evaluation.
  
  
  CONCLUSIONS
  The clinical course of most patients was benign, but in approximately 20% of the subjects a liver disease developed. Particular attention should be given to autoimmune liver diseases in subjects with positive autoantibodies. In addition, lifestyle factors such as weight gain and alcohol consumption were associated with the manifestation of liver diseases.
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Strasser
authors.affiliation: Department of Internal Medicine, Oberndorf Hospital, Oberndorf, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlmayr
authors.affiliation: Department of Pathology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Heike
authors.initials: H
authors.lastname: Haufe
authors.affiliation: Hepatology Unit, Clinic Beau-Site, Bern and Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.affiliation: Third Department of Medicine, Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Department of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Feldman
authors.affiliation: Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.|Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weghuber
authors.affiliation: Department of Internal Medicine, Oberndorf Hospital, Oberndorf, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Elmar
authors.initials: E
authors.lastname: Aigner
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D001317:Austria / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000175:diagnosis / Q000453:epidemiology; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015430:Weight Gain
keywords: NAFLD; autoimmune hepatitis; liver; liver biopsy; normal histology