A systematic review and meta-analysis of HCV clearance.

Gauthiez, Emeline; Habfast-Robertson, Ines; Rüeger, Sina; Kutalik, Zoltan; Aubert, Vincent; Berg, Thomas; Cerny, Andreas; Gorgievski, Meri; George, Jacob; Heim, Markus H; Malinverni, Raffaele; Moradpour, Darius; Müllhaupt, Beat; Negro, Francesco; Semela, David; Semmo, Nasser; Villard, Jean; Bibert, Stéphanie; Bochud, Pierre-Yves (2017). A systematic review and meta-analysis of HCV clearance. Liver international, 37(10), pp. 1431-1445. Wiley 10.1111/liv.13401

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Gorgievski, Meri and Semmo, Nasser

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1478-3231

Publisher:

Wiley

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

31 Jan 2018 16:28

Last Modified:

28 May 2018 12:36

Publisher DOI:

10.1111/liv.13401

PubMed ID:

28261910

Uncontrolled Keywords:

hepatitis C host genetics spontaneous clearance sustained virological response

BORIS DOI:

10.7892/boris.109491

URI:

https://boris.unibe.ch/id/eprint/109491

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