title: Outcome of sustained virological responders with histologically advanced chronic hepatitis C.
abstract: Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n = 309) or who experienced breakthrough or relapse (BT/R; n = 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR = 0.17, 95% confidence interval [CI] = 0.06-0.46) or development of liver-related morbidity/mortality (HR = 0.15, 95% CI = 0.06-0.38) or HCC (HR = 0.19, 95% CI = 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR.
  
  
  CONCLUSIONS
  Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC.
authors.affiliation: Division of Gastroenterology, University of California Irvine, Irvine, CA, USA. timothy.morgan@va.gov
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Snow
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: De Santo
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a