A systematic review and meta‐analysis of HCV clearance

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 DQB1*02, DQB1*03, DRB1*04 and DRB1*11. In the meta‐analysis of 16 studies of KIR genes and their HLA‐ligands, KIR2DS3 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 (EIF2AK2, IFNAR2, ITPA, MBL2, MX1, OASL, SPP1, TGFB1, TNK2) with response to interferon‐based therapy. Meta‐analysis of 141 studies confirmed the association of IFNL3/4 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.

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

“…however, a meta-analysis suggested that KIR2DS3 was a protective factor associated with both HCV spontaneous clearance and treatment-induced clearance (Gauthiez et al, 2017 (Naiyer et al, 2017). In present study, we did not find any associations between KIR2DL1, KIR2DL3, KIR2DS1 and their HLA-C1 ligands.…”

“…In 2015, De Re, V., et al . (De Re et al, ; Gauthiez et al, ) and Fitzmaurice et al (Fitzmaurice et al, ) reported that KIR2DS3 was a risk factor associated with CHC in Italians, as well as in Irish women and Swiss people; however, a meta‐analysis suggested that KIR2DS3 was a protective factor associated with both HCV spontaneous clearance and treatment‐induced clearance (Gauthiez et al, ). Kusnierczyk et al reported that KIR2DS2 may contribute to the susceptibility to CHC in Polish Caucasians (Kusnierczyk et al, ), while Sung, et al suggested it might be associated with HCV clearance in the Korean population (Sung et al, ).…”

Influence of HLA‐B18 on liver fibrosis progression in a cohort of HIV/HCV coinfected individuals

“…Moreover, after the discovery in 2008 of the strong association between the hypersensitivity to Abacavir and HLA‐B57, usually HIV‐infected patients get tested for HLA haplotypes before starting therapy with Abacavir. Research show that either HLA class I and HLA class II seem also implicated in HCV infection outcome . In fact, HLA haplotypes influence the development of an effective CD8+ and NK cells response.…”

“…Research show that either HLA class I and HLA class II seem also implicated in HCV infection outcome. 12 In fact, HLA haplotypes influence the development of an effective CD8+ and NK cells response. It can be hypothesized that CD8+ and NK cells binding of intracellular HCV-related antigen, expressed on the surface of cells in association with HLA class I proteins, is determinant to rise an effective immune response against the HCV-infected liver cells.…”

Host-Related Predictors of Persistence of Hepatitis C Virus Infection

“…A major feature of HCV is the interindividual variability in the ability to clear the virus, either spontaneously or after treatment [13]. Knowledge of the variation between population subgroups in terms of the prevalence of spontaneous clearance could inform policy decisions on the use of direct-acting antivirals [8].…”