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Hepatitis C Cirrhosis Patients with Sustained Treatment Response Have Lower Risk of Death


Hepatitis C patients with cirrhosis who achieve sustained virological response to interferon-based therapy have a reduced risk of all-cause mortality, liver-related death or transplantation, liver cancer, and liver failure compared with non-responders, according to a study described in the December 26, 2012, issue of JAMA.

Adriaan van der Meerfrom Erasmus University Medical Center in Rotterdam and an international team of colleagues looked at the association between sustained virological response -- or continued undetectable viral load after completion of therapy (traditionally assessed 24 weeks post-treatment) -- and adverse clinical outcomes for hepatitis C patients with advanced fibrosis.

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver fibrosis, cirrhosis (scarring), hepatocellular carcinoma (HCC, a form of liver cancer), liver transplantation, and liver-related death. An estimated 25% of the approximately 3.5 million people in the U.S. with chronic hepatitis C (some prevalence estimates reach 4 million) have cirrhosis, and the proportion is expected to increase to 45% by 2030, the study authors noted as background. Treatment with interferon-based therapy can get rid of the virus, but its long-term effects on liver health are not fully understood.

This retrospective analysis included 530 chronic hepatitis C patients at 5 large tertiary care hospitals in Canada and Europe who started interferon-based therapy between 1990 and 2003; follow-up was completed between January 2010 and October 2011. They were treated with conventional interferon monotherapy, conventional interferon plus ribavirin, or pegylated interferon plus ribavirin in roughly equal proportions.

Most participants (70%) were men and the median age was 48 years. All had Ishak fibrosis scores of 4 (27%), 5 (19%), or 6 (54%), indicating advanced fibrosis or cirrhosis. The median follow-up period was just over 8 years (ranging from 6 to 11 years).


  • 192 study participants (36%) achieved sustained virological response at 24 weeks post-treatment (SVR24).
  • 13 patients who achieved SVR and 100 people without SVR died due to any cause.
  • Of the deaths among non-responders, 70% were due to liver-related causes, 15% to non-liver-related causes, and 15% to unknown causes.
  • 10-year cumulative all-cause mortality rates were 8.9% for the SVR group compared with 26.0% for those without SVR, a statistically significant difference (P < 0.001).
  • 3 patients with SVR and 103 people without SVR either died due to liver-related causes or underwent liver transplantation.
  • 10-year cumulative rates of liver-related death or transplantation (combined) was 1.9% for the SVR group versus 27.4% for non-responders, again a significant difference (P < 0.001).
  • 7 participants with SVR and 76 people without SVR developed HCC.
  • 10-year cumulative incidence rates for liver cancer were 5.1% vs 21.8%, respectively, again significant (P < 0.001).
  • 4 patients with SVR and 111 people without SVR experienced liver failure.
  • 10-year cumulative incidence rates for liver failure were 2.1% vs 29.9%, also significant (P < 0.001).
  • In a time-dependent multivariate analysis, SVR was associated with:

o   Lower risk of all-cause mortality: hazard ratio (HR) 0.26, or a 74% reduction;

o   Lower risk of liver-related death or transplantation: HR 0.06, or a 94% reduction.

  • Other baseline factors significantly associated with all-cause mortality included older age, HCV genotype 3, diabetes, and history of heavy alcohol use.

Based on these findings, the researchers concluded, "Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality."

"In our international, multicenter, long-term follow-up study, SVR was associated with prolonged overall survival," they elaborated in their discussion. "The risk of all-cause mortality was almost 4-fold lower in patients with SVR compared with patients without SVR."

"Our study with a long follow-up duration demonstrated a lower risk for all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis who achieved SVR," they added. "In addition, we were able to further establish and quantify the risk reduction of HCC, liver failure, and liver-related mortality or liver transplantation in patients with SVR."

The authors noted that their study may have selected for a relatively healthy group of cirrhotic patients, since interferon-based treatment has traditionally been considered contraindicated for people with severe liver damage. New direct-acting antiviral agents enable higher cure rates with a shorter duration of therapy, and some have shown promise for patients with cirrhosis.



AJ van der Meer, BJ Veldt, JJ Feld, et al. Association between Sustained Virological Response and All-cause Mortality among Patients with Chronic Hepatitis C and Advanced Liver Fibrosis. JAMA 308(24):2584-2593. December 26, 2012.

Other Source

American Medical Association. Sustained Virological Response Associated With Improved Survival For Certain Patients With Chronic Hepatitis C Virus Infection. Media advisory. December 25, 2012.