title: Hepatitis C treatment failure is associated with increased risk of hepatocellular carcinoma.
abstract: Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV) reduces risk of hepatocellular carcinoma (HCC), but there is little information regarding how treatment failure (TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study (CHeCS-an observational study based in four large US health systems, with up to 7 years of follow-up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582 (43%) of these achieved sustained virological response (SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50-2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all-cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48, CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause mortality (aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93 for TF patients).
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Loralee B
authors.initials: LB
authors.lastname: Rupp
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Holmberg
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moorman
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Spradling
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Eyasu H
authors.initials: EH
authors.lastname: Teshale
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Yueren
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Center for Health Research, Geisinger Health System, Danville, PA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Boscarino
authors.affiliation: Center for Health Research, Kaiser Permanente-Northwest, Portland, OR, Portland.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schmidt
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Lois E
authors.initials: LE
authors.lastname: Lamerato
authors.affiliation: Center for Health Research, Kaiser Permanente-Hawai'i, Waipahu, HI, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Trinacty
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Sheri
authors.initials: S
authors.lastname: Trudeau
authors.affiliation: Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D005006:Ethnicity; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D017211:Treatment Failure; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents
keywords: antiviral treatment; sustained virological response; treatment failure