1. A Systematic Review and Meta-Analysis of HCV Clearance
- Author
-
Stéphanie Bibert, Andreas Cerny, Meri Gorgievski, Thomas Berg, Jean Villard, Emeline Gauthiez, David Semela, Jacob George, Nasser Semmo, Beat Müllhaupt, Vincent Aubert, Sina Rüeger, Zoltán Kutalik, Francesco Negro, Darius Moradpour, Ines Habfast-Robertson, Raffaele Malinverni, Markus H. Heim, and Pierre-Yves Bochud
- Subjects
0301 basic medicine ,Candidate gene ,SVR ,Genotype ,Sustained Virologic Response ,Hepatitis C virus ,Single-nucleotide polymorphism ,Hepacivirus ,Human leukocyte antigen ,ddc:616.07 ,medicine.disease_cause ,Antiviral Agents ,Polymorphism, Single Nucleotide ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Receptors, KIR ,HLA Antigens ,Interferon ,Odds Ratio ,medicine ,Humans ,ddc:616 ,Hepatology ,ddc:617 ,business.industry ,Hepatitis C ,medicine.disease ,Virology ,3. Good health ,spontaneous clearance ,Phenotype ,Treatment Outcome ,030104 developmental biology ,host genetics ,Host-Pathogen Interactions ,Immunology ,030211 gastroenterology & hepatology ,ITPA ,hepatitis C ,business ,medicine.drug - 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.
- Published
- 2017