title: 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: OBJECTIVE
  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 ± 2.0vs2.3 ± 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.
  
  
  CONCLUSIONS
  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.
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Caterina
authors: C
authors: Sagnelli
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Marco
authors: M
authors: Merli
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Caterina
authors: C
authors: Uberti-Foppa
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Hamid
authors: H
authors: Hasson
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Anna
authors: A
authors: Grandone
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Grazia
authors: G
authors: Cirillo
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Stefania
authors: S
authors: Salpietro
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Carmine
authors: C
authors: Minichini
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Mario
authors: M
authors: Starace
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Emanuela
authors: E
authors: Messina
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Patrizia
authors: P
authors: Morelli
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Emanuele
authors: E
authors: Miraglia Del Giudice
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Adriano
authors: A
authors: Lazzarin
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Nicola
authors: N
authors: Coppola
authors: Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery, F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy.
authors: Evangelista
authors: E
authors: Sagnelli
mesh_terms: D000328:Adult; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D060085:Coinfection; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D008565:Membrane Proteins; C419195:TM6SF2 protein, human
keywords: Human immunodeficiency virus/hepatitis C virus co-infection; Liver biopsy; Liver histology; Liver steatosis; TM6SF2