title: Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.
abstract: The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ∼20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive literature search in MEDLINE and EMBASE for 'genotype 4' was conducted in November 2013. Abstracts from American Association for the Study of Liver Diseases, Asian Pacific Study of the Liver, Digestive Disease Week, and European Association for the Study of the Liver in 2012/2013 were reviewed. Inclusion criteria were original studies with at least 25 treatment-naive HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were coinfection with HIV, hepatitis B virus, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (P<0.05) and I statistic (>50%). We included 51 studies (11 102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% [95% confidence interval (CI): 50-55%] (Q-statistic=269.20, P<0.05; I=81.43). On subgroup analyses, SVR was significantly associated with lower viral load, odds ratio (OR) 3.05 (CI: 1.80-5.17, P<0.001); mild fibrosis, OR 3.17 (CI: 2.19-4.59, P<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI: 2.87-7.69, P<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI: 2.31-11.73, P<0.001). HCV-4 patients treated with PEG IFN+RBV may expect SVR rates of ∼50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.
authors.affiliation: aSchool of Medicine at the University of California, San Diego bDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California cDepartment of Internal Medicine, Rush University Medical Center, Chicago, Illinois dSchool of Medicine at Stony Brook University, Stony Brook, New York, USA.
authors.forename: Brittany E
authors.initials: BE
authors.lastname: Yee
authors.forename: Nghia H
authors.initials: NH
authors.lastname: Nguyen
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Philip
authors.initials: P
authors.lastname: Vutien
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Wong
authors.forename: Glen A
authors.initials: GA
authors.lastname: Lutchman
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology; D011110:Polymorphism, Genetic; D012107:Research Design; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons