Severe nonalcoholic steatohepatitis and type 2 diabetes: liver histology after weight loss therapy in a randomized clinical trial

Abstract

Objective: To evaluate the effectiveness of the fast weight loss method on liver steatosis, fibrosis, inflammation, glycemic and lipid features and body composition in patients with severe nonalcoholic steatohepatitis (NASH) and type 2 diabetes (T2D).

Methods: A 24 week open prospective randomized controlled clinical trial including 80 adult patients (aged 40-65 years) was performed. The patients after randomization were divided into two groups: the main group followed the fast weight loss method; the control group received conventional drug treatment. The fast weight loss method included calorie restriction, salt intake, walking and sexual self-restraint. The conventional drug therapy included vitamin E, orlistat, pioglitazone hydrochloride, atorvastatin, lisinopril, benzodiazepines and anti-inflammatory agents. Primary endpoints were: ultrasound and histology suggestive of steatohepatitis, hepatic enzymes, weight loss, 2 hour oral glucose tolerance test and glycosylated hemoglobin A1C (HbA1c). Secondary endpoints were: blood pressure and lipids.

Results: A total of 83% patients completed the study. In the main group weight lost was 7-16 kg (10-20% from baseline) for 8-10 weeks. In this group weight was lost due to reduction of fat mass only. The main vs. control group showed higher decrease in fat mass from baseline (p < .001). Ultrasound imaging and liver histological scoring system evidenced significant improvement in liver steatosis/fibrosis in the main group (p < .001). In the main vs. control group weight lost at 24 weeks led to positive laboratory changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), 2 hour oral glucose tolerance test (OGTT), HbA1c, Homeostasis Model Assessment insulin resistance indexes (HOMA-IR), blood pressure (BP), cholesterol, triglycerides, bilirubin total and blood hemoglobin (p = .01). The fast weight loss in the patients adequately led to decrease in symptomatic drugs up to complete abolition.

Conclusions: The study showed benefits of the fast weight loss method improving in steatosis/fibrosis and biochemical/metabolic outcomes in patients with severe NASH and T2D.

Keywords: Severe nonalcoholic steatohepatitis; fast weight loss; fibrosis; type 2 diabetes.