Causes of Death Among People with Hepatitis B and C

SUMMARY
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.

By James Learned

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:

	82,034 people (63.7%) with HCV monoinfection;
	42,480 people (33%) with HBV monoinfection;
	3285 people (2.6%) with HBV/HCV coinfection;
	269 people (0.2%) with HIV/HBV coinfection;
	620 people (0.5%) with HIV/HCV coinfection; and
	38 people (< 0.1%) with HIV/HBV/HCV triple infection.

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

A total of 6201 people died between 1992 and 2006, with mortality rates differing widely across groups:

	HCV monoinfection: 6%;
	HBV monoinfection: 3%;
	HBV/HCV coinfection: 7%;
	HIV/HBV coinfection: 23%;
	HIV/HCV coinfection: 15%.

The leading cause of death for the HBV monoinfected group was neoplasms (tumors), most frequently HCC, followed by lung cancer and lymphoid cancer.

Cancer rates were significantly higher among people with HBV monoinfection than among those with HCV monoinfection.

People with HBV were significantly more likely to have HCC than those with HCV.

In contrast, the leading cause of death in the HCV monoinfected group was not specifically liver-related -- 72% of deaths were the result of drug overdose or suicide.

The rate of all-cause mortality was significantly higher for the HCV monoinfected group than for the HBV monoinfected group.

After taking into account age and sex, people with HCV monoinfection had a 2.5 times higher mortality rate compared with the overall population of New South Wales.

However, the number of drug-related deaths among people with HCV in 2002 was approximately half that seen prior to 2000, and rates have since remained low and stable.

Drug-related deaths of people with HCV during 2002-2006 were significantly lower than those reported during 1997-2001.

For women with HBV or HCV, the risks of death due to drug-related causes and, significantly, liver disease, was higher than it was for men.

Rates of liver-related death increased with age in both the HBV monoinfected and HCV monoinfected groups.

Among people with HBV/HCV coinfection, rates of all-cause death were considerably higher than among people with HBV or HCV monoinfection.

Compared with the overall population of New South Wales, the mortality rate for people with coinfection (HBV/HCV, HIV/HBV, or HIV/HCV) was 4 to 24 times higher.

People coinfected with HIV also had a markedly higher risk of death compared to other infected groups.

	People with HIV/HBV coinfection had a mortality rate 10 times higher than those with HBV monoinfection.
	People with HIV/HCV coinfection were at least 3 times more likely to die than their HCV monoinfected counterparts.

Most deaths among HIV/HBV and HIV/HCV coinfected people were HIV-related (70% and 61%, respectively).

People with HIV/HBV/HCV triple infection had by far the highest rate of death due to all causes.

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.