Causes of Death Among People with Hepatitis B and C

June 19, 2011

http://www.hivandhepatitis.com/hep_c/news/2011/0617_2011_a.html

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 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,

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.

June 19, 2011