Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2015; 21(25): 7860-7868
Published online Jul 7, 2015. doi: 10.3748/wjg.v21.i25.7860
Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome
Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Evangelia Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, Dimitri P Mikhailidis
Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2nd Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece
Evangelia Katsiki, Department of Pathology, Hippocration Hospital, 54124 Thessaloniki, Greece
Panagiotis Anagnostis, Department of Endocrinology, Hippocration Hospital, 54124 Thessaloniki, Greece
Dimitri P Mikhailidis, Department of Clinical Biochemistry (Vascular Disease Prevention Clinic), Royal Free Campus, University College London Medical School, University College London, NW3 2QG London, United Kingdom
Dimitri P Mikhailidis, Department of Surgery, Royal Free Campus, University College London Medical School, University College London, NW3 2QG London, United Kingdom
Author contributions: Kargiotis K designed the study and recruited patients; Athyros VG designed the study, followed-up patients and wrote the paper; Giouleme O performed biopsies; Kastiki N followed-up patients; Katsiki E did pathology; Anagnostis P recruited patients; Boutari C followed up patients; Doumas M wrote the paper; Karagiannis A designed the protocol; Mikhailidis DP interpreted the results wrote the paper; all authors approved the final version of the paper.
Conflict-of-interest statement: This study was carried out independently; no company or institution supported it financially. Some of the authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies. Mikhailidis DP has given talks and attended conferences sponsored by Merck, Sharp & Dohme, AstraZeneca and Genzyme.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dimitri P Mikhailidis, MD, FFPM, FRCP, FRCPath Academic Head, Department of Clinical Biochemistry (Vascular Disease Prevention Clinic), Royal Free Campus, University College London Medical School, University College London, Pond Street, NW3 2QG London, United Kingdom. mikhailidis@aol.com
Telephone: +44-20-78302258 Fax: +44-20-78302235
Received: December 23, 2014
Peer-review started: December 25, 2014
First decision: March 10, 2015
Revised: March 31, 2015
Accepted: May 27, 2015
Article in press: May 27, 2015
Published online: July 7, 2015
Processing time: 196 Days and 19 Hours
Abstract

AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.

METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.

RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had MetS by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.

CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Metabolic syndrome; Dyslipidaemia; Rosuvastatin; Fasting blood glucose; Serum uric acid

Core tip: We treated 20 patients with metabolic syndrome (MetS) and biopsy proven non-alcoholic steatohepatitis (NASH) with rosuvastatin monotherapy for one year. Repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, and normalization of liver enzymes, lipid profile and blood glucose; no patient had MetS at the end of the study. These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and serum uric acid levels, if confirmed by larger studies, may reduce the risk of vascular and liver morbidity and mortality in NASH patients.