Overall mortality from both liver-related disease and non-liver conditions — including some cancers is significantly increased in people with chronic hepatitis C virus (HCV) infection compared with uninfected individuals, according to a study published in the July 17, 2012, advance online edition of the Journal of Infectious Diseases, according to the Hepatitis C Trust, a charity for people with Hepatitis C, based in London.

Over years or decades, chronic hepatitis C can progress to serious liver disease including cirrhosis, hepatocellular carcinoma, and end-stage liver failure. But the effect of HCV infection on non-liver-related illness and death has not been extensively studied.

Mei-Hsuan Lee from Academia Sinica in Taipei, Chien-Jen Chen from the Genomic Research Center, and fellow investigators with the R.E.V.E.A.L.-HCV Study Group looked at associations between HCV infection and liver-related and non-liver deaths.

The researchers assessed the presence of hepatitis B surface antigen (HBsAg), antibodies against HCV, and serum HCV RNA viral load levels at study entry. After excluding individuals with hepatitis B or HIV co-infection, the analysis included 18,541 HCV antibody negative and 1095 HCV antibody positive people.

Information about deaths was obtained by computerized linkage to national death certificate data from 1991 to 2008.


  • Among HCV antibody positive participants, 69.4% had detectable serum HCV RNA.
  • A total of 2394 deaths occurred during an average follow-up period of 16.2 years.
  • People who were HCV antibody positive had higher mortality rates due to both liver-related and non-liver (extrahepatic) diseases compared with HCV antibody negative people.
  • In a multivariate analysis, the adjusted hazard ratio (HR) for all causes of death was 1.89, or nearly double the risk.
  • The adjusted HR for liver-related death was 12.48, or more than 12-fold higher risk.
  • The adjusted HR for extrahepatic death was a much lower but still significant 1.35.

HCV infection was associated with increased risk for several extrahepatic causes of death:

  • Thyroid cancer: adjusted HR 8.22;
  • Prostate cancer: adjusted HR 4.19;
  • Esophageal cancer: adjusted HR 4.08;
  • Kidney disease (nephritis, nephrotic syndrome, or nephrosis): adjusted HR 2.77;
  • Circulatory system diseases: adjusted HR 1.50.

HCV antibody positive people with detectable HCV RNA had significantly higher mortality from both liver-related and extrahepatic diseases than those with undetectable viral load.

Further analysis showed that people with HCV antibodies but undetectable HCV RNA had mortality rates statistically similar to those of uninfected individuals.

Based on these findings, the study authors concluded that close monitoring of people with detectable HCV antibodies or genetic material “is essential for the prediction of mortality associated with hepatitis C.”

This study indicates that even chronic hepatitis C patients with no symptoms have a higher likelihood of death, and that treatment that reduces HCV viral load may lower mortality, underling the importance of timely HCV testing and therapy.

“The findings implied that the serum HCV RNA level is an important marker for clinical decisions in the management of HCV-infected patients,” Chen said in a press release issued by the Infectious Diseases Society of America, which publishes the journal.

In an accompanying editorial, Kenrad Nelson from Johns Hopkins Bloomberg School of Public Health pointed out that overall mortality was significantly higher among HCV-infected compared with uninfected individuals even when looking at people from the same communities, thereby minimizing potential bias.

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