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.

Trial registration: ClinicalTrials.gov identifier: NCT01700075.

Keywords:

• Severe nonalcoholic steatohepatitis
• type 2 diabetes
• fast weight loss
• fibrosis

Transparency

Declaration of funding

Ministry of Health of the Republic of Kazakhstan (grant for years 2009–2011 with trial registration #0109RK00079 and code O.0390, National Center for Scientific and Technical Information of the Republic of Kazakhstan).

Declaration of financial/other relationships

K.O., B.B., K.M., G.B., Kh.M. and B.D. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors thank the funding body, the staff of the Scientific Research Institute of Cardiology and Internal Diseases, Professor Abylaiuly Zh and Professor Fedotovskikh GV for consultation. The authors acknowledge the writing assistance of Professor Sandro Vento.

Consent for publication

Our manuscript does not contain any individual person’s data in any form. All authors of the manuscript affirm that they had access to the study data and reviewed and approved the final manuscript.

Availability of data and material

Brief preliminary results were reported as an abstract within the 21st Conference of the Asian Pacific Association for the Study of the Liver in 2011 (Bangkok, Thailand), that was published in Hepatol Int 2011;5:8-37.

Additional information

Notes on contributors

Kuat Oshakbayev

K.O.: design and performance, patient recruitment and treatment, data collection, bibliography review, scientific analysis, statistical advancing, scientific executor, writing, editing and revision. B.B.: study design, patient recruitment and treatment, writing the Discussion, bibliography and paper review. K.M.: design and performance, pathologist and histology study, scientific analysis, bibliography and paper review. G.B.: treatment of the patients, preparation e-version data collection in Excel, bibliography and paper review, scientific analysis, statistical advancing, writing the Methods. Kh.M.: study design, scientific analysis, paper scientific review, writing the Methods. B.D.: pathologist and histology study, writing the Methods/Results, paper review and print.

Bakytzhan Bimbetov

K.O.: design and performance, patient recruitment and treatment, data collection, bibliography review, scientific analysis, statistical advancing, scientific executor, writing, editing and revision. B.B.: study design, patient recruitment and treatment, writing the Discussion, bibliography and paper review. K.M.: design and performance, pathologist and histology study, scientific analysis, bibliography and paper review. G.B.: treatment of the patients, preparation e-version data collection in Excel, bibliography and paper review, scientific analysis, statistical advancing, writing the Methods. Kh.M.: study design, scientific analysis, paper scientific review, writing the Methods. B.D.: pathologist and histology study, writing the Methods/Results, paper review and print.

Kenzhegul Manekenova

K.O.: design and performance, patient recruitment and treatment, data collection, bibliography review, scientific analysis, statistical advancing, scientific executor, writing, editing and revision. B.B.: study design, patient recruitment and treatment, writing the Discussion, bibliography and paper review. K.M.: design and performance, pathologist and histology study, scientific analysis, bibliography and paper review. G.B.: treatment of the patients, preparation e-version data collection in Excel, bibliography and paper review, scientific analysis, statistical advancing, writing the Methods. Kh.M.: study design, scientific analysis, paper scientific review, writing the Methods. B.D.: pathologist and histology study, writing the Methods/Results, paper review and print.

Gulnara Bedelbayeva

K.O.: design and performance, patient recruitment and treatment, data collection, bibliography review, scientific analysis, statistical advancing, scientific executor, writing, editing and revision. B.B.: study design, patient recruitment and treatment, writing the Discussion, bibliography and paper review. K.M.: design and performance, pathologist and histology study, scientific analysis, bibliography and paper review. G.B.: treatment of the patients, preparation e-version data collection in Excel, bibliography and paper review, scientific analysis, statistical advancing, writing the Methods. Kh.M.: study design, scientific analysis, paper scientific review, writing the Methods. B.D.: pathologist and histology study, writing the Methods/Results, paper review and print.

Khalit Mustafin

K.O.: design and performance, patient recruitment and treatment, data collection, bibliography review, scientific analysis, statistical advancing, scientific executor, writing, editing and revision. B.B.: study design, patient recruitment and treatment, writing the Discussion, bibliography and paper review. K.M.: design and performance, pathologist and histology study, scientific analysis, bibliography and paper review. G.B.: treatment of the patients, preparation e-version data collection in Excel, bibliography and paper review, scientific analysis, statistical advancing, writing the Methods. Kh.M.: study design, scientific analysis, paper scientific review, writing the Methods. B.D.: pathologist and histology study, writing the Methods/Results, paper review and print.

Bibazhar Dukenbayeva

K.O.: design and performance, patient recruitment and treatment, data collection, bibliography review, scientific analysis, statistical advancing, scientific executor, writing, editing and revision. B.B.: study design, patient recruitment and treatment, writing the Discussion, bibliography and paper review. K.M.: design and performance, pathologist and histology study, scientific analysis, bibliography and paper review. G.B.: treatment of the patients, preparation e-version data collection in Excel, bibliography and paper review, scientific analysis, statistical advancing, writing the Methods. Kh.M.: study design, scientific analysis, paper scientific review, writing the Methods. B.D.: pathologist and histology study, writing the Methods/Results, paper review and print.