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Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.

ABSTRACT: AIM:To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review. METHODS:The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur. RESULTS:We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFN?4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine. CONCLUSION:Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.

SUBMITTER: Severson TJ

PROVIDER: S-EPMC4970479 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.

Severson Tyler J TJ Besur Siddesh S Bonkovsky Herbert L HL

World journal of gastroenterology 20160801 29

<h4>Aim</h4>To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.<h4>Methods</h4>The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this tim ...[more]

PMID: 27547017

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Project description:BACKGROUND:Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD. METHODS:We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications. RESULTS:We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight. CONCLUSIONS:Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.

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Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.

Publications

Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.

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