People Who Naturally Clear Hepatitis C Virus Have Lower Risk of Death than Chronic Patients

SUMMARY: People with hepatitis C virus (HCV) who spontaneously clear the infection without treatment have a low risk of death, less than 10% over 5 years, according to a Danish study published in the July 2010 Journal of Hepatology. Individuals who develop chronic hepatitis C, however, have an elevated risk of overall and liver-related mortality, including deaths due to primary liver cancer.

By Liz Highleyman

Most experts estimate that approximately one-quarter to one-third of people initially infected with HCV will naturally clear the virus without treatment thanks to an effective immune response. Among those with persistent infection, however, HCV can over years or decades cause serious liver disease including cirrhosis and hepatocellular carcinoma, a form of primary liver cancer.

Research has shown that people with chronic hepatitis C have a higher risk of liver-related death, but outcomes among people who were once infected but naturally cleared the virus have not been extensively studied.

In the present analysis, Lars Haukali Omland and fellow investigators with the DANVIR Cohort Study examined the association between chronic HCV replication and mortality among Danish patients who tested positive for HCV antibodies.

This nationwide cohort study looked at more than 6000 patients with at least 1 HCV RNA (genetic material) viral load measurement available after testing positive for HCV antibodies between 1996 and 2005. To capture long-term outcomes, eligible participants needed to be alive for at least 1 year after HCV RNA assessment.

The researchers estimated mortality rate ratios (MRRs) for overall mortality and sub-distribution hazard ratios (SDHRs) for cause-specific mortality, after controlling for patient sex, age, co-existing conditions, heavy alcohol use, injection drug use, and income.

Results

• Of the 6292 patients in the study, 37% spontaneously cleared HCV, while 63% developed chronic infection.
• Overall 5-year survival rates were 92% for participants who cleared the virus, compared with 86% for those with chronic infection.
• Chronic HCV infection was associated with higher overall mortality compared with viral clearance (MRR 1.55).
• Chronic infection was also associated with a more than a 2-fold greater risk of liver-related death (SDHR 2.42).
• In particular, chronic HCV infection greatly increased -- by more than 16-fold -- the risk of death due to primary liver cancer (SDHR 16.47). 

Based on these findings, the study authors concluded, "Patients with chronic HCV infection are at higher risk of death than patients who cleared the infection."

"The substantial association found between chronic HCV infection and death from primary liver cancer supports early initiation of antiviral treatment in chronically HCV-infected patients," they recommended.

Investigator affiliations: Department of Infectious Diseases, Rigshospitalet, Copenhagen; Department of Clinical Biochemistry, Aalborg Hospital; Department of Clinical Epidemiology, Aarhus University Hospital; Department of Clinical Immunology, Odense University Hospital; Department of Clinical Immunology and Blood Bank, Rigshospitalet, Copenhagen; Department of Clinical Immunology, Viborg Region Hospital; Department of Clinical Immunology, Hospital of Southern Jutland, Region of Southern Denmark; Department of Clinical Microbiology, Vejle Hospital; Department of Infectious Diseases, Odense University Hospital, Denmark; Department of Epidemiology, Boston University School of Public Health, Boston, MA.

8/31/10

Reference
LH Omland, H Krarup, P Jepsen, and others (DANVIR Cohort Study). Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study. Journal of Hepatology 53(1): 36-42 (Abstract). July 2010.

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