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Metabolism. 2017 Jun;71:17-32. doi: 10.1016/j.metabol.2017.02.014. Epub 2017 Mar 4.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement.

Author information

1
2nd Prop. Department of Internal Medicine, Hippocration Hospital, Medical School of Aristotle University Thessaloniki, Greece. Electronic address: vathyros@gmail.com.
2
Department of Internal Medicine, Division of Endocrinology, University of Patras Medical School, Patras, Greece.
3
Lipid Clinic, Cardiology Department, Tzaneio Hospital, Piraeus, Greece.
4
4th Prop. Department of Internal Medicine, Hippocration Hospital, Division of Gastroenterology and Hepatology, Medical School of Aristotle University Thessaloniki, Greece.
5
2nd Prop. Department of Internal Medicine, Hippocration Hospital, Medical School of Aristotle University Thessaloniki, Greece.
6
Department of Internal Medicine University Hospital of Crete, University of Crete Medical School, Heraklion, Greece.
7
Department of Cardiology Medical School, University Hospital of Ioannina, Ioannina, Greece.
8
Department of Internal Medicine, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
9
1st Department of Internal Medicine, Gastroenterology and Hepatology Section, AHEPA Hospital, Aristotle University Medical School, Thessaloniki, Greece.
10
First Cardiology Department, AHEPA Hospital, Medical School, Aristotle University Thessaloniki, Greece.
11
3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University Thessaloniki, Greece.
12
1st Cardiology Clinic, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
13
2nd Prop. Propedeutic Department of Internal Medicine, Hippocration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
14
2nd Department of Cardiology, University General Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
15
Department of Cardiology, Euroclinic, Athens, Greece.
16
2nd Department of Internal Medicine-Diabetology, Hippocration Hospital, Aristotle University Thessaloniki, Medical School, Thessaloniki, Greece.
17
Atherothrombosis Research Centre/Department of Chemistry, University of Ioannina, Ioannina, Greece.
18
1st Prop. Department of Internal Medicine, AHEPA Hospital, Aristotle University Medical School, Thessaloniki, Greece.
19
Endocrinology Department, St. Luke's Hospital, Thessaloniki, Greece.
20
Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK.
21
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Abstract

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

KEYWORDS:

Ezetimibe; Hepatocellular cancer (HCC); Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic steatohepatitis (NASH); Pioglitazone; Statins

PMID:
28521870
DOI:
10.1016/j.metabol.2017.02.014
[Indexed for MEDLINE]

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