A systematic review and meta‐analysis of HCV HCV clearance

摘要

Abstract While hepatitis C exemplifies the role of host genetics in infectious diseases outcomes, there is no comprehensive overview of polymorphisms influencing spontaneous and/or treatment‐induced hepatitis C virus clearance. We performed a systematic review and meta‐analysis of host polymorphisms associated with these phenotypes. Literature search was conducted using combinations of keywords in three databases. Studies were reviewed and relevant data systematically extracted for subsequent meta‐analyses. Polymorphisms from candidate gene studies were tested in two cohorts of HCV ‐infected patients with available genomic data. The literature search yielded 8'294 citations, among which 262 studies were selected. In the meta‐analysis of 27 HLA studies, the most significant associations with spontaneous hepatitis C virus clearance included DQB 1*02, DQB 1*03, DRB 1*04 and DRB 1*11. In the meta‐analysis of 16 studies of KIR genes and their HLA ‐ligands, KIR 2 DS 3 was associated with both spontaneous and treatment‐induced clearance, and the HLA ‐C2 ligand with failure to spontaneously clear the virus. In a pooled analysis of 105 candidate genes and two genome‐wide association studies, we observed associations of single nucleotide polymorphisms from nine genes ( EIF 2 AK 2, IFNAR 2, ITPA , MBL 2, MX 1, OASL , SPP 1, TGFB 1, TNK 2) with response to interferon‐based therapy. Meta‐analysis of 141 studies confirmed the association of IFNL 3/4 polymorphisms with spontaneous and treatment‐induced hepatitis C virus clearance, even in previously underpowered groups, such as hepatitis C virus genotypes 2/3‐infected patients. This study may contribute to a better understanding of hepatitis C virus immunopathogenesis and highlights the complex role of host genetics in hepatitis C virus clearance.