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The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9273Article in journal (Refereed) Published
Abstract [en]

The impact of Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant, which causes hepatocellular fat retention by altering lipoprotein secretion, on liver damage and metabolic traits in chronic hepatitis C patients is still debated. We performed a systematic review and meta-analysis to clarify this relationship. Four studies with a total of 4325 patients were included. The risk of histologically-determined advanced steatosis, fibrosis, and cirrhosis (but not of severe inflammation) were increased in carriers of the TM6SF2 variant (P < 0.05). Unlike the inconsistent association with steatosis severity, due to the confounding effect of infection by the genotype-3 hepatitis C virus, the TM6SF2 variant was robustly associated with advanced fibrosis (OR = 1.07; 95% confidence interval [CI] = 1.01-1.14) and in particular with cirrhosis (OR = 2.05; 95% CI = 1.39-3.02). Regarding metabolic features, individuals positive for the TM6SF2 variant exhibited 5.8-12.0% lower levels of circulating triglycerides and non-HDL cholesterol (P < 0.05). Carriers of the variant were leaner, but there was high heterogeneity across studies (I-2 = 97.2%). No significant association was observed between the TM6SF2 variant and insulin resistance or hepatitis C viral load (both P > 0.05). In conclusion, the TM6SF2 E167K variant promotes the development of steatosis, fibrosis and cirrhosis in patients with chronic hepatitis C. Conversely, this variant reduces circulating atherogenic lipid fractions.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 7, article id 9273
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Gastroenterology and Hepatology Clinical Medicine
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URN: urn:nbn:se:kth:diva-214502DOI: 10.1038/s41598-017-09548-9ISI: 000408440800008PubMedID: 28839198Scopus ID: 2-s2.0-85028072952OAI: oai:DiVA.org:kth-214502DiVA, id: diva2:1146256
Note

QC 20171002

Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2017-10-02Bibliographically approved

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