Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis

Adriaan J. Van Der Meer, Bart J. Veldt, Jordan J. Feld, Heiner Wedemeyer, Jean François Dufour, Frank Lammert, Andres Duarte-Rojo, E. Jenny Heathcote, Michael P. Manns, Lorenz Kuske, Stefan Zeuzem, W. Peter Hofmann, Robert J. De Knegt, Bettina E. Hansen, Harry L.A. Janssen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1275 Scopus citations

Abstract

Context: Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death. Objective: To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis. Design, Setting, and Patients: An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011. Main Outcome Measures: All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation. Results: The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P<.001). In time-dependent multivariate Cox regression analysis, SVR was associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P<.001) and reduced risk of liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02-0.19; P<.001), the latter occurring in 3 patients with SVR and 103 without SVR. The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9% (95% CI, 0.0%-4.1%) with SVR and 27.4% (95% CI, 22.0%-32.8%) without SVR (P<.001). There were 7 patients with SVR and 76 without SVR who developed HCC (10-year cumulative incidence rate, 5.1%; 95% CI, 1.3%-8.9%; vs 21.8%; 95% CI, 16.6%-27.0%; P<.001), and 4 patients with SVR and 111 without SVR experienced liver failure (10-year cumulative incidence rate, 2.1%; 95% CI, 0.0%-4.5%; vs 29.9%; 95% CI, 24.3%-35.5%; P<.001). Conclusion: Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.

Original languageEnglish (US)
Pages (from-to)2584-2593
Number of pages10
JournalJAMA
Volume308
Issue number24
DOIs
StatePublished - Dec 26 2012

ASJC Scopus subject areas

  • General Medicine

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