Original article—liver, pancreas, and biliary tract
A Sustained Virologic Response Reduces Risk of All-Cause Mortality in Patients With Hepatitis C

https://doi.org/10.1016/j.cgh.2011.03.004Get rights and content

Background & Aims

The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities.

Methods

From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009.

Results

HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002).

Conclusions

An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.

Section snippets

Methods

We used data automatically extracted from the VA's electronic medical record into the Clinical Case Registry to identify veterans with HCV receiving care at any VA medical facility.16 A patient was included in the primary investigation if the following criteria were met: (1) had HCV genotype (GT) 1, 2, or 3; (2) started pegylated interferon (PEG-IFN)/ribavirin between January 20, 2001, and June 30, 2007; (3) stopped PEG-IFN/ribavirin treatment by June 30, 2008; and (4) had a HCV RNA test result

Results

We identified 22,942 patients who started and stopped treatment with PEG-IFN/ribavirin by the date criteria. Patients were excluded from the primary cohort for human immunodeficiency virus co-infection (649), hepatocellular carcinoma before treatment (64), an undetectable posttreatment HCV RNA but no test 12 weeks or more after the treatment end date (380), and no posttreatment HCV RNA test (4985). Sixty-five percent of the patients with no posttreatment HCV RNA test had a treatment duration of

Discussion

In this large US cohort of patients with HCV treated with PEG-IFN/ribavirin in routine medical practice, achieving SVR was associated with a significantly reduced risk of all-cause mortality for patients with GT1, GT2, and GT3, after adjusting for numerous baseline patient characteristics and comorbidities. Previous research has focused on liver-related mortality and thus any potential benefit of SVR on all-cause mortality, particularly in populations with substantial competing risk, has not

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    Conflicts of interest The authors disclose no conflicts.

    Funding All authors are supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Public Health and Environmental Hazards.

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