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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
Marco Merli, Caterina Uberti-Foppa, Hamid Hasson, Stefania Salpietro, Emanuela Messina, Patrizia Morelli, Adriano Lazzarin, Department of InfectiousDiseases, Vita-Salute University, San Raffaele ScientificInstitute, 20127 Milan, Italy
Anna Grandone, Grazia Cirillo, Emanuele Miraglia Del Giudice, Department of Pediatrics, Second University of Naples, 80131 Naples, Italy
Nicola Coppola, Carmine Minichini, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
Author contributions: Sagnelli C, Grandone A, Coppola N, Sagnelli E made substantial contributions to the conception and design, drafting the article or revising it critically for important intellectual content; and final approval of the version to be published; Merli M, Cirillo G, Salpietro S, Messina E, Morelli P, Coppola N collected the data, and final approval of the version to be published; Uberti-Foppa C, Hasson H, Miraglia Del Giudice E, Lazzarin A revised the article critically for important intellectual content, and made final approval of the version to be published; Minichini C and Starace M performed laboratory analyses.
Conflict-of-interest statement: All the authors of the manuscript declare that they have no conflict of interest in connection with this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Evangelista Sagnelli, Professor, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, 80131 Naples, Italy.
evangelistasagnelli@libero.it
Telephone: +39-81-5666719 Fax: +39-81-5666207
Received: June 21, 2016
Peer-review started: June 22, 2016
First decision: July 13, 2016
Revised: August 6, 2016
Accepted: August 23, 2016
Article in press: August 23, 2016
Published online: October 14, 2016
Processing time: 113 Days and 10.9 Hours
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 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.
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.
Core tip: The transmembrane 6 superfamily member 2 (TM6SF2) E167K variant has been identified as an independent predictor of severe liver steatosis in patients with hepatitis C virus (HCV)-related chronic hepatitis (CH) lacking human immunodeficiency virus (HIV) infection. We analyzed the impact of the TM6SF2 E167K variant on the liver histology of 167 HIV/HCV co-infected patients with CH. The TM6SF2 E167K variant was found to be an independent predictor of severe fibrosis, while an independent association with severe steatosis was demonstrated only for patients with a non-3 HCV genotype.
