A systematic review and meta‐analysis of HCV clearance

Gauthiez, Emeline and Habfast-Robertson, Ines and Rüeger, Sina and Kutalik, Zoltan and Aubert, Vincent and Berg, Thomas and Cerny, Andreas and Gorgievski, Meri and George, Jacob and Heim, Markus H. and Malinverni, Raffaele and Moradpour, Darius and Müllhaupt, Beat and Negro, Francesco and Semela, David and Semmo, Nasser and Villard, Jean and Bibert, Stéphanie and Bochud, Pierre-Yves and Swiss Hepatitis C. Cohort Study, . (2017) A systematic review and meta‐analysis of HCV clearance. Liver International, 37 (10). pp. 1431-1445.

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Official URL: https://edoc.unibas.ch/69559/

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hepatologie > Hepatologie (Heim)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hepatologie > Hepatologie (Heim)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Feb 2019 17:43
Deposited On:26 Feb 2019 17:43

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