Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis
ABSTRACT Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear.
To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH.
We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date.
All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents.
Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used.
When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58% versus 33%). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials.
Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.
Full-textDOI: · Available from: Reza Malekzadeh, Jan 31, 2014
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: A systematic review (SR) is a research methodology that involves a comprehensive search for and analysis of relevant studies on a specific topic. A strict and objective research process is conducted that comprises a systematic and comprehensive literature search in accordance with predetermined inclusion/exclusion criteria, and an assessment of the risk of bias of the selected literature. SRs require a multidisciplinary approach that necessitates cooperation with clinical experts, methodologists, other experts, and statisticians. A meta-analysis (MA) is a statistical method of quantitatively synthesizing data, where possible, from the primary literature selected for the SR. Review articles differ from SRs in that they lack a systematic methodology such as a literature search, selection of studies according to strict criteria, assessment of risk bias, and synthesis of the study results. The importance of evidence-based medicine (EBM) in the decision-making for public policy has recently been increasing thanks to the realization that it should be based on scientific research data. SRs and MAs are essential for EBM strategy and evidence-based clinical practice guidelines. This review addresses the current trends in SRs and MAs in the field of hepatology via a search of recently published articles in the Cochrane Library and Ovid-MEDLINE.06/2014; 20(2):137-150. DOI:10.3350/cmh.2014.20.2.137
- [Show abstract] [Hide abstract]
ABSTRACT: In this study, we aimed to investigate the effect and action mechanisms of pineapple leaf phenols (PLPs) on liver fat metabolism in high-fat diet-fed mice. Results show that PLP significantly reduced abdominal fat and liver lipid accumulation in high-fat diet-fed mice. The effects of PLP were comparable with those of FB. Furthermore, at the protein level, PLP upregulated the expression of carnitine palmitoyltransferase 1 (CPT-1), whereas FB had no effects on CPT-1 compared with the HFD controls. Regarding mRNA expression, PLP mainly promoted the expression of CPT-1, PGC1a, UCP-1, and AMPK in the mitochondria, whereas FB mostly enhanced the expression of Ech1, Acox1, Acaa1, and Ehhadh in peroxisomes. PLP seemed to enhance fat metabolism in the mitochondria, whereas FB mainly exerted the effect in peroxisomes. In addition, p-coumaric acid (CA), one of the main components from PLP, significantly inhibited fat accumulation in oleic acid-induced HepG2 cells. CA also significantly upregulated CPT-1 mRNA and protein expressions in HepG2 cells. We, firstly, found that PLP enhanced liver fat metabolism by upregulating CPT-1 expression in the mitochondria and might be promising in treatment of fatty liver diseases as alternative natural products. CA may be one of the active components of PLP.Evidence-based Complementary and Alternative Medicine 08/2014; 2014:903258. DOI:10.1155/2014/903258 · 1.88 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Non-alcoholic fatty liver disease is an emerging liver disease in Western countries and the most frequent cause of incidental elevation of serum liver enzymes. Dyslipidaemia is frequently observed in patients with non-alcoholic fatty liver disease, and treatment of dyslipidaemia plays a critical role in the overall management of these patients. Moreover, coronary artery disease remains the most common cause of death. Statins are effective lipid-lowering agents, associated with a lowering the risk of cardiovascular events in several interventional randomized clinical trials. However, statins are often underused in patients with non-alcoholic fatty liver disease and many physicians are concerned about the prescription of statins to patients with unexplained persistent elevation of liver enzymes or active liver disease. Based on currently available data, statin therapy, at low-to-moderate doses, seems to be safe and has low liver toxicity. Treatment of dyslipidaemia in patients with non-alcoholic fatty liver disease is recommended and may also improve liver function tests. In these patients, the risks of not taking statins could outweigh the risks of taking the drug. Conversely, the usefulness of statins for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis is still a matter of debate and randomized clinical trials of adequate size and duration are required.Digestive and Liver Disease 09/2014; DOI:10.1016/j.dld.2014.07.170 · 2.89 Impact Factor