Author information
1First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. . alexandra.feldman@outlook.com.
2Second Department of Medicine, Paracelsus Medical University Salzburg, Austria. bernhard@wernly.net.
3First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. georg.strebinger@outlook.com.
4First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria;St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. sebastian.eder@gmail.com.
5First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. stephan.zandanell@gmail.com.
6Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Austria; Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland. david.niederseer@gmx.at.
7First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. m.strasser@salk.at.
8Institute of Pathology, Paracelsus Medical University, Salzburg, Austria. h.haufe@salk.at.
9Institute of Pathology, Paracelsus Medical University, Salzburg, Austria. k.sotlar@salk.at.
10First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. b.paulweber@salk.at.
11Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Austria. c.datz@kh-oberndorf.at.
12First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria. e.aigner@salk.at.
Abstract
Background and aims: Although non-alcoholic fatty liver disease (NAFLD) is linked to obesity, a proportion of lean subjects also have NAFLD with potentially distinct clinical features. We studied the outcome of lean NAFLD subjects.
Methods: 299 consecutive patients (215 male, 84 female, 49.5 ± 13.5years) with biopsy-proven NAFLD and a follow-up of 8.4 years (±4.1; range: 0.9-18.0) were stratified by body mass index (BMI) at the time of liver biopsy: lean (BMI ≤25.0 kg/m, n=38), overweight (BMI 25.0-29.9 kg/m2, n=165), obese (BMI ≥30.0 kg/m2, n=93). A control group of 1,013 subjects (547 male, 52.4 ± 5.8) was used for comparison. The time to the event was recorded. Multivariable Cox regression analyses were performed to assess associations with 10-year-mortality. Hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated.
Results: Age and gender were similar, while components of the metabolic syndrome were less frequent in lean subjects. The proportion of subjects with significant fibrosis and the number of subjects with cirrhosis was increased in lean subjects while the proportion of non-alcoholic steatohepatitis was not different. Mortality in the NAFLD groups was significantly higher than in the control group. Multivariable analysis adjusting for age, gender, and glucose confirmed lower mortality in overweight (aHR 0.21; 95% CI 0.07-0.62, p=0.005) and in obese (aHR 0.22; 95% CI 0.06-0.76, p=0.02) compared to lean subjects. Further adjustment for fibrosis weakened the difference between lean and obese (p=0.12) while the difference to overweight subjects remained intact (p=0.01).
Conclusion: Lean subjects with NAFLD have a high risk of liver-related death. Our data support that lean NAFLD subjects deserve particular attention with regard to clinical follow-up.