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

Caterina Sagnelli, Marco Merli, Caterina Uberti-Foppa, Hamid Hasson, Anna Grandone, Grazia Cirillo, Stefania Salpietro, Carmine Minichini, Mario Starace, Emanuela Messina, Patrizia Morelli, Emanuele Miraglia Del Giudice, Adriano Lazzarin, Nicola Coppola, Evangelista Sagnelli

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Abstract

AIM 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. METHODS 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). RESULTS 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 HCVgenotype 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. CONCLUSION 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.

Original languageEnglish
Pages (from-to)8509-8518
Number of pages10
JournalWorld Journal of Gastroenterology
Volume22
Issue number38
DOIs
Publication statusPublished - Oct 14 2016

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Hepacivirus
Liver Cirrhosis
Genotype
Fibrosis
HIV
Coinfection
Liver
Chronic Hepatitis
Alanine Transaminase
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Biopsy

Keywords

  • Human immunodeficiency virus/hepatitis C virus co-infection
  • Liver biopsy
  • Liver histology
  • Liver steatosis
  • TM6SF2

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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; Merli, Marco; Uberti-Foppa, Caterina; Hasson, Hamid; Grandone, Anna; Cirillo, Grazia; Salpietro, Stefania; Minichini, Carmine; Starace, Mario; Messina, Emanuela; Morelli, Patrizia; Del Giudice, Emanuele Miraglia; Lazzarin, Adriano; Coppola, Nicola; Sagnelli, Evangelista.

In: World Journal of Gastroenterology, Vol. 22, No. 38, 14.10.2016, p. 8509-8518.

Research output: Contribution to journalArticle

Sagnelli, C, Merli, M, Uberti-Foppa, C, Hasson, H, Grandone, A, Cirillo, G, Salpietro, S, Minichini, C, Starace, M, Messina, E, Morelli, P, Del Giudice, EM, Lazzarin, A, Coppola, N & Sagnelli, E 2016, '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', World Journal of Gastroenterology, vol. 22, no. 38, pp. 8509-8518. https://doi.org/10.3748/wjg.v22.i38.8509
Sagnelli, Caterina ; Merli, Marco ; Uberti-Foppa, Caterina ; Hasson, Hamid ; Grandone, Anna ; Cirillo, Grazia ; Salpietro, Stefania ; Minichini, Carmine ; Starace, Mario ; Messina, Emanuela ; Morelli, Patrizia ; Del Giudice, Emanuele Miraglia ; Lazzarin, Adriano ; Coppola, Nicola ; Sagnelli, Evangelista. / 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. In: World Journal of Gastroenterology. 2016 ; Vol. 22, No. 38. pp. 8509-8518.
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abstract = "AIM 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. METHODS 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). RESULTS 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 HCVgenotype 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. CONCLUSION 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.",
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T1 - 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

AU - Sagnelli, Caterina

AU - Merli, Marco

AU - Uberti-Foppa, Caterina

AU - Hasson, Hamid

AU - Grandone, Anna

AU - Cirillo, Grazia

AU - Salpietro, Stefania

AU - Minichini, Carmine

AU - Starace, Mario

AU - Messina, Emanuela

AU - Morelli, Patrizia

AU - Del Giudice, Emanuele Miraglia

AU - Lazzarin, Adriano

AU - Coppola, Nicola

AU - Sagnelli, Evangelista

PY - 2016/10/14

Y1 - 2016/10/14

N2 - AIM 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. METHODS 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). RESULTS 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 HCVgenotype 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. CONCLUSION 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.

AB - AIM 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. METHODS 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). RESULTS 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 HCVgenotype 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. CONCLUSION 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.

KW - Human immunodeficiency virus/hepatitis C virus co-infection

KW - Liver biopsy

KW - Liver histology

KW - Liver steatosis

KW - TM6SF2

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