Published online Oct 14, 2016. doi: 10.3748/wjg.v22.i38.8509
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
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.
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.