Hepatitis C Ups All-Cause Death Rate, SVR Reduces Mortality

People with chronic hepatitis C virus (HCV) infection have more than twice the risk of death due to all causes, but sustained response to interferon-based therapy cuts the risk, according to 2 recently published studies.

Mortality

Over years or decades, chronic hepatitis C can progress to advanced cirrhosis, liver cancer, and end-stage liver disease.

As described in the July 15, 2011, issue of Clinical Infectious Diseases, researchers from the University of Maryland and Duke University evaluated all cause, liver-related, and non-liver-related mortality among people with HCV in a large U.S. general population study.

The analysis included 9378 people who participated in the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative prospective cohort study of adults aged 17-59 years. The researchers used data from the NHANES Linked Mortality File, looking at people whose HCV status was assessed from 1988 through 1994, with mortality followed through 2006.

Results

• A total of 614 deaths were recorded over a median follow-up period of about 15 years.
• Among 203 people with chronic hepatitis C, there were 44 deaths, including 9 attributed to liver-related causes.
• The remaining 35 deaths were due to HIV, diabetes, heart disease, cancer, and other causes.
• After adjusting for other risk factors, people with chronic HCV infection had a 2.4 times higher all-cause mortality rate.
• People with HCV had a 26.5 times higher rate of death due to liver-related causes.
• For non-liver-related causes, the mortality rate remained 1.79 times higher among people with HCV, but this did not reach statistical significance.
• Extrapolating from the sample population, the researchers estimated that 2.46 million U.S. adults with chronic hepatitis C experienced an estimated 31,163 deaths from all causes and 9569 liver-related deaths per year
• An estimated 57.8% of all deaths and 96.2% of liver-related deaths in this group were attributable to HCV.

"Chronic HCV all-cause mortality is more than twice that of HCV-negative individuals," the investigators concluded. "This suggests that those with chronic HCV infection are at a higher risk of death even after accounting for liver-related morbidity and should be closely monitored."

"This should reinforce the importance of preventive measures, particularly among individuals at-risk for acquiring the disease, as well as early diagnosis, and improving access to care for those already infected, even in the absence of liver disease," lead author Samer El-Kamary said in a press release issued by the Infectious Diseases Society of America.

"While a hepatitis C infection itself may not be the cause of death, patients with the disease may be at a higher risk of dying due to other high-risk behaviors that may have also caused the infection," he continued. "Furthermore, it is possible that other co-morbidities like diabetes and cardiovascular disease could get worse if there is an underlying hepatitis C infection."

"Given the low cost for hepatitis C tests, perhaps it would be advisable to consider more liberal early screening of patients if there is any suspicion of infection so they can be referred for treatment as early as possible," El-Kamary recommended.

Sustained Response

If having hepatitis C increases the risk of death, successful treatment may reduce mortality, as El-Kamary suggests.

In a study reported in the June 2011 issue of Clinical Gastroenterology and Hepatology, Lisa Backus and colleagues looked at the impact of sustained virological response, or a cure, on all-cause mortality.

The study included all patients at U.S. Department of Veterans Affairs (VA) facilities who were infected with HCV genotypes 1 (n=12,166), 2 (n=2904), or 3 (n=1794), started treatment with pegylated interferon plus ribavirin between January 2001 and June 2007, and had available post-treatment HCV RNA test results to assess SVR (continued undetectable viral load 6 months after completion of therapy).

People with HIV coinfection or liver cancer were excluded. Other co-morbidities, however, were common overall. The researchers used mortality data from VA and non-VA sources available through 2009.

Results

• SVR rates of were 35%, 72%, and 62%, for patients with HCV genotypes 1, 2, and 3, respectively.
• During a median follow-up period of about 4 years, 1119 genotype 1 patients, 220 genotype 2 patients, and 196 genotype 3 patients died.
• In a genotype-specific multivariate analysis controlling for demographic factors, co-morbidities, and laboratory and treatment characteristics, SVR was significantly associated with reduced mortality risk for each genotype:

o      Genotype 1: hazard ratio 0.70;

o      Genotype 2: hazard ratio 0.64;

o      Genotype 3: hazard ratio 0.51.

Based on these findings, the study authors concluded, "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 co-morbidities."

"These findings extend the prior observations that SVR reduced liver-related mortality and show an all-cause mortality reduction for each of 3 common genotypes," they elaborated in their discussion. "Moreover, these findings strongly support an important and clinically significant benefit of HCV antiviral treatment irrespective of the HCV genotype, patient age, and co-morbidities."

Investigator affiliations:

El-Kamary study: Department of Epidemiology and Public Health, Department of Pediatric, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD; Division of Infectious Diseases, Department of Pediatrics, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC.

Backus study: Center for Quality Management in Public Health, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.

7/15/11

References

SS El-Kamary, R Jhaveri, and MD Shardell. All-Cause, Liver-Related, and Non-Liver-Related Mortality Among HCV-Infected Individuals in the General US Population. Clinical Infectious Diseases 53(2):150-157 (abstract). July 15, 2011.

LI Backus, DB Boothroyd, BR Phillips, et al. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clinical Gastroenterology and Hepatology 9(6):509-516.e1 (abstract). June 2011. 

Other Source

Infectious Diseases Society of America. Analysis Finds Mortality from All Causes Higher Among Hepatitis C-Infected. Press release. July 10, 2011.

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