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

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.

• Authors: 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
• Journal: JAMA (JAMA) Vol. 308 Issue 24 Pg. 2584-93 (Dec 26 2012) ISSN: 1538-3598 [Electronic] United States
• PMID: 23268517 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferons

Topics

• Adult
• Antiviral Agents (therapeutic use)
• Canada (epidemiology)
• Cause of Death
• Europe (epidemiology)
• Female
• Follow-Up Studies
• Hepatitis C, Chronic (complications, drug therapy, mortality, virology)
• Humans
• Interferons (therapeutic use)
• Liver Cirrhosis (complications, virology)
• Liver Failure (complications, virology)
• Male
• Middle Aged
• Viremia