Publikation

A systematic review and meta-analysis of HCV clearance

Wissenschaftlicher Artikel/Review - 30.03.2017

Bereiche
PubMed
DOI

Zitation
Gauthiez E, Moradpour D, Mullhaupt B, Negro F, Semela D, Semmo N, Villard J, Bibert S, Bochud P, Malinverni R, Heim M, Habfast-Robertson I, Rüeger S, Kutalik Z, Aubert V, Berg T, Cerny A, Gorgievski M, George J, Swiss Hepatitis C Cohort Study. A systematic review and meta-analysis of HCV clearance. Liver Int 2017; 37:1431-1445.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Liver Int 2017; 37
Veröffentlichungsdatum
30.03.2017
eISSN (Online)
1478-3231
Seiten
1431-1445
Kurzbeschreibung/Zielsetzung

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.