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TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype.

ABSTRACT: To evaluate the impact of the Glu167Lys (E167K) transmembrane 6 superfamily member 2 (TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients.The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K (rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males (73.6%), the median age was 40.7 years and the immunological condition good (median CD4+ cells/mm3 = 505.5).The 17 patients with the TM6SF2 E167K variant, compared with the 150 with TM6SF2-E/E, showed higher AST (P = 0.02) and alanine aminotransferase (P = 0.02) and higher fibrosis score (3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCV-genotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167K in non-3 HCV genotypes. No association between the TM6SF2 E167K variant and severe liver necroinflammation was observed.In HIV/HCV coinfection the TM6SF2 E167K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.

SUBMITTER: Sagnelli C

PROVIDER: S-EPMC5064032 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype.

Sagnelli Caterina C Merli Marco M Uberti-Foppa Caterina C Hasson Hamid H Grandone Anna A Cirillo Grazia G Salpietro Stefania S Minichini Carmine C Starace Mario M Messina Emanuela E Morelli Patrizia P Miraglia Del Giudice Emanuele E Lazzarin Adriano A Coppola Nicola N Sagnelli Evangelista E

World journal of gastroenterology 20161001 38

<h4>Aim</h4>To evaluate the impact of the Glu167Lys (E167K) transmembrane 6 superfamily member 2 (TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients.<h4>Methods</h4>The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner ...[more]

PMID: 27784963

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Project description:Hepatic steatosis (HS) is common in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, but the independent contributions of HCV and HIV to HS are unclear. Magnetic resonance imaging and spectroscopy were used to measure visceral adipose tissue (VAT) and liver fat fraction (LFF) (total lipids/[total lipids + water]) in 356 adults: 57 with HCV monoinfection, 70 with HIV/HCV coinfection, 122 with HIV monoinfection, and 107 with neither infection. Participants who were infected with HCV genotype 3 were excluded because of the genotype's reported steatogenic effects. For prevalence estimates, HS was defined as LFF ≥ 0.05. We estimated the association of HIV and HCV status with LFF using multivariable linear regression, adjusting for demographics, lifestyle, and metabolic factors including the homeostasis model assessment estimate of insulin resistance (HOMA-IR) and liver fibrosis defined using the aspartate aminotransferase-to-platelet ratio index (APRI). The prevalence of HS was highest in the uninfected (33%) and HIV-monoinfected (28%), followed by the HCV-monoinfected (19%) and HIV/HCV-coinfected (11%) (P = 0.003 across groups). Compared with uninfected participants-and after adjusting for demographics, lifestyle, and metabolic factors-HIV monoinfection, HCV monoinfection, and HIV/HCV coinfection were associated with 19% (95% confidence interval [CI], -39% to 6%), 38% (95% CI, -55% to -12%), and 42% (95% CI, -59% to -18%) lower LFF, respectively. HCV monoinfection and HIV/HCV coinfection remained strongly associated with lower LFF after further adjusting for APRI, and results were unchanged after excluding subjects with suspected cirrhosis. Among the entire cohort, Hispanic ethnicity, male sex, VAT, and HOMA-IR were independently associated with greater LFF.ConclusionContrary to expectations, HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjusting for demographics, lifestyle, metabolic factors, and hepatic fibrosis. Our findings suggest that non-genotype 3 HCV infection may be protective against HS. The mechanisms by which this occurs and the impact of HCV treatment on HS requires further investigation. (Hepatology 2017;65:853-863).

Dataset Information

TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype.

Publications

TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype.

Similar Datasets

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