title: Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.
abstract: OBJECTIVE
  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 20(th), 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 3(rd) treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6(th) treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3(rd) treatment month. No patient had MetS by the 9(th) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kargiotis
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Vasilios G
authors.initials: VG
authors.lastname: Athyros
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Giouleme
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Katsiki
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Katsiki
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Anagnostis
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Boutari
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Doumas
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Asterios
authors.initials: A
authors.lastname: Karagiannis
authors.affiliation: Konstantinos Kargiotis, Vasilios G Athyros, Olga Giouleme, Niki Katsiki, Panagiotis Anagnostis, Chrysoula Boutari, Michael Doumas, Asterios Karagiannis, 2 Prop. Department of Internal Medicine, Medical School, Aristotle University, Hippocration Hospital, 54124 Thessaloniki, Greece.
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006115:Greece; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014527:Uric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014527:Uric Acid; D000068718:Rosuvastatin Calcium
keywords: Dyslipidaemia; Fasting blood glucose; Metabolic syndrome; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Rosuvastatin; Serum uric acid