title: Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.
abstract: Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.
authors.affiliation: Centre for Population Health, Burnet Institute, Melbourne, Vic., Australia.|School of Population Health and Preventive Medicine, Monash University, Melbourne, Vic., Australia.|Department of Infectious Diseases, The Alfred Hospital, Melbourne, Vic., Australia.
authors.forename: J S
authors.initials: JS
authors.lastname: Doyle
authors.affiliation: Hannover Medical School, Hannover, Germany.|Hep-Net Study House: German Network of Competence on Viral Hepatitis, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Deterding
authors.affiliation: Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Grebely
authors.affiliation: Hannover Medical School, Hannover, Germany.|Hep-Net Study House: German Network of Competence on Viral Hepatitis, Hannover, Germany.|German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Centre for Population Health, Burnet Institute, Melbourne, Vic., Australia.|School of Population Health and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
authors.forename: R
authors.initials: R
authors.lastname: Sacks-Davis
authors.affiliation: Centre for Population Health, Burnet Institute, Melbourne, Vic., Australia.
authors.forename: T
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Matthews
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Rice
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Morris
authors.affiliation: Tufts Medical School, Boston, MA, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: McGovern
authors.affiliation: Harvard Medical School, Boston, MA, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: CRCHUM, Université de Montréal, Montreal, QC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: Lloyd
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Page
authors.affiliation: Hannover Medical School, Hannover, Germany.|Hep-Net Study House: German Network of Competence on Viral Hepatitis, Hannover, Germany.|German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany.
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Centre for Population Health, Burnet Institute, Melbourne, Vic., Australia.|School of Population Health and Preventive Medicine, Monash University, Melbourne, Vic., Australia.|Department of Infectious Diseases, The Alfred Hospital, Melbourne, Vic., Australia.
authors.forename: M E
authors.initials: ME
authors.lastname: Hellard
authors.affiliation: Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: G J
authors.initials: GJ
authors.lastname: Dore
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001315:Australia; D002170:Canada; D060085:Coinfection / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D015658:HIV Infections / Q000150:complications / Q000821:virology; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C579163:IFNL4 protein, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: acute infection; hepatitis C virus; recently acquired infection; virological response