Causes of Death Among People with Hepatitis B and C

alt

Deaths due to most liver-related causes dropped among people with hepatitis B, and people with hepatitis C were less likely to die of drug-related causes, but mortality due to hepatocellular carcinoma remained stable, according to a large Australian study. Coinfection with HIV increased mortality significantly.

Over time chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection can progress to advanced liver disease, including life-threatening liver failure and hepatocellular carcinoma (HCC), a form of liver cancer. These viruses are often transmitted through shared drug injection equipment and people with hepatitis B and C are therefore also at elevated risk for death due to drug-related causes such as overdose.

In a retrospective study described in the May 11, 2011, Journal of Hepatology, Scott Walter and colleagues analyzed specific causes of death among a population-based cohort of people with hepatitis B or C to examine trends in mortality and identify areas of excess risk.

The study authors looked at medical records of people with hepatitis B or C in New South Wales, Australia, between 1992 and 2006. New South Wales is the most populous state in Australia, including almost one-third of the country's population.

Using data from the state's Notifiable Diseases Database, the researchers determined trends in mortality among people with HBV monoinfection, HCV monoinfection, HBV/HCV coinfection, HIV/HBV coinfection, HIV/HCV coinfection, and HIV/HBV/HCV triple infection. Australia law mandates reporting of HIV, HBV, and HCV diagnoses, allowing the opportunity to conduct an accurate population-based assessment of people living with these diseases.

A previous population-based study found large increases in rates of death among people with hepatitis B and an alarmingly jump in mortality among people with hepatitis C. The high HCV-related mortality was largely attributed to deaths due to drug-related causes, outnumbering deaths caused by liver disease. In the current study, the researchers extended their previous work to examine recent trends in HBV- and HCV-related deaths, including the impact of coinfection.

The study looked at medical records of 128,726 patients:

The cohort included 60% men and 40% women; 90% of people with HIV were men, and 72% of those coinfected with HBV/HCV were men. All patients had been diagnosed with viral hepatitis between 1994 and 2002. If an individual died within 6 months of diagnosis, he or she was excluded from the analysis (1367 people).

Results

In their discussion of their analysis, the researchers described the supply and purity of opiates that contributed to drug-related deaths, specifically the shortage and higher price of heroin in late 2000 and early 2001. The decrease in the supply of heroin and its high price has been credited with fewer drug-related deaths during that period. However, the researchers noted, "[O]ur study found that rather than return to pre-2001 levels, rates of drug-related deaths have remained low in 2002 to 2006."

"Wider reaching interventions such as the needle and syringe exchange programs (NSPs) and harm reduction campaigns delivered through the NSPs may also have contributed to the maintenance of improved drug-related mortality since 2001 among those infected with HCV," they continued.

In addition, they wrote, "The moderate decline in non-HCC liver disease mortality among people with HBV monoinfection and the decline in age-specific rates of liver-related death with younger cohorts suggest that improved HBV antiviral therapy may have reduced the risk of death from decompensated cirrhosis."

The authors suggested that the availability of antiviral drugs for the treatment of hepatitis B may also have contributed to a decrease in hepatocellular carcinoma, although this did not reach statistical significance. "The study identified a positive trend in non-HCC liver-related deaths among those infected with HBV, consistent with improvements in HBV treatment and uptake."

Unfortunately, pegylated interferon was only licensed in Australia in 2006, so most people with hepatitis C were either not on treatment or on thrice-weekly conventional interferon plus ribavirin. Lack of the latest state-of-the-art treatment -- which now includes direct-acting antiviral agents as well as pegylated interferon/ribavirin -- may have contributed to the high rate of death among people with HCV.

Investigator affiliations: National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia; New South Wales Department of Health, Sydney, Australia; Storr Liver Unit, Westmead Hospital and Westmead Millennium Institute, University of Sydney, Sydney, Australia; Australian Government Department of Health and Ageing; NSW Cancer Council STREP Grant (SRP08-03).

6/17/11

Reference
S Walter, H Thein, J Amin, et al. Trends in mortality after diagnosis of hepatitis B or C infection: 1992-2006. Journal of Hepatology 54(5):879-886 (abstract). May 2011.