Hepatitis C surpasses HIV as a cause of death in the US

This article is more than 12 years old. Click here for more recent articles on this topic

Deaths in the US due to hepatitis C now exceed those caused by HIV, according to research published in the Annals of Internal Medicine.  The study showed that there is a downward trend in HIV-related mortality, but incidence of deaths due to hepatitis C is increasing.

“This analysis shows the rapidly increasing number of deaths among HCV [hepatitis C virus]-infected persons, which now surpass deaths among HIV-related persons,” write the authors.

Mortality was concentrated in the “baby boomer” generation, individuals aged between 45 to 64 years. The investigators believe this pattern “portends a large and ever-increasing health care burden.”


adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

quality adjusted life year (QALY)

Used in studies dealing with cost-effectiveness and life expectancy, this gives a higher value to a year lived with good health than a year lived with poor health, pain or disability. 



The majority of hepatitis C infections in the US are undiagnosed and a separate study published in the same journal shows that targeted hepatitis C screening of individuals in this age group would be cost-effective and could avert up to 121,000 deaths compared to current risk-based screening.

Infection with hepatitis B and hepatitis C are leading causes of chronic liver disease and liver cancer in the US. In 2007, they were listed among the 15 leading causes of death.

Investigators used information recorded on death certificates to plot trends in mortality due to hepatitis B and hepatitis C between 1999 and 2007. These trends were compared to the incidence of HIV-related deaths over the same period. Analysis was also undertaken to determine the factors associated with hepatitis-related deaths in 2007.

Approximately 21.8 million death certificates were included in the investigators’ analysis.

There was a non-significant decrease in hepatitis B-related mortality of 0.02 deaths per 100,000 person years. However, the incidence of hepatitis C-related deaths increased by a significant 0.18 per 100,000 person years (p = 0.002). This compared to a reduction in HIV-related mortality of 0.21 per 100,000 person years (p = 0.001). Indeed, in 2007 mortality associated with hepatitis C infection surpassed that from HIV infection.

Hepatitis B was documented as the underlying cause of 724 deaths (0.03%) and as the single underlying or contributing cause in 1815 deaths (0.07%; adjusted mortality rate, 0.56 deaths per 100,000 person years). 

Infection with hepatitis C virus was documented as the underlying cause of 6605 deaths (0.27%) and as the underlying or contributing cause of 15,106 deaths (0.62%; adjusted mortality rate, 4.58 deaths per 100,000 person years).

This hepatitis C-related mortality exceeded that attributed to HIV. Infection with HIV was listed as the underlying cause of death on 11,332 death certificates (0.47%), and the underlying or contributory cause in 12,734 deaths (0.52%; adjusted mortality rate, 4.16 deaths per 100,000 person years).

The investigators believe that these data grossly underestimate the true burden of hepatitis C-related mortality. “HCV infection and HCV-related chromic liver disease have remained consistently poorly ascertained and, thus, under-reported on death certificates.”

A number of co-morbid conditions were strongly related to death attributed to hepatitis B. These included chronic liver disease (AOR = 34.4; 95% CI, 31.0-38.1), co-infection with hepatitis C (AOR = 31.5; 95% CI, 28.0-35.4), HIV infection (AOR = 4.0; 95% CI, 3.2-5.1) and alcohol-related illness (AOR = 3.7; 95% CI, 3.2-4.2).

Co-morbid conditions related to hepatitis C mortality were chronic liver disease (AOR = 32.1; 95% CI, 31.0-33.3), co-infection with hepatitis B (AOR = 29.9; 95% CI, 26.5-33.6), alcohol-related illness (AOR = 4.6; 95% CI, 4.4-4.8) and HIV co-infection (AOR = 1.8; 95% CI, 1.6-2.0).

Deaths attributable to viral hepatitis infection were clustered in the “baby boomer” generation, individuals born between 1945 and 1964. In all, 59% of hepatitis B-related deaths were involved persons aged between 45 and 64 years as did 73% of deaths attributed to hepatitis C.

“Few diseases of such morbidity and mortality in the United States have received so little public attention and funding as chronic viral hepatitis,” comment the authors.

Current screening strategies are risk-based, targeting individuals with a history of injecting drug use. The investigators suggest this has been “notably unsuccessful, as few have been screened for risk and are still only tested when they have symptoms…few physicians ask about the major risk factor for HCV, injecting drug use, and few interviewees wish to admit this behavior.”

Because almost 75% of hepatitis C-related deaths involved individuals aged between 45 and 64 the researchers suggest “screening efforts that target middle-aged persons may be profitable.”

A second study published in the same edition of the Annals showed that such a strategy could be cost-affect and save tens of thousands of lives.

Researchers wanted to ascertain the effectiveness, benefits and cost of three approaches to hepatitis C screening and treatment. These were:

  • Model 1: Risk-based screening, and hepatitis C therapy including pegylated interferon and ribavirin.

  • Model 2: Age-based screening (45 to 64 years) in routine care, with hepatitis C treatment with pegylated interferon and ribavirin.

  • Model 3: Age-based testing, and hepatitis C triple hepatitis C therapy including a protease inhibitor, pegylated interferon and ribavirin.

The authors calculated that 2.4 million hepatitis C-infected individuals had a primary care consultation in 2006 and that 50% of these infections were undiagnosed.

Risk-based screening would lead to 135,000 patients receiving hepatitis C therapy, which would be successful for 53,000 patients. A total of 592,000 patients would die of liver-related causes.

Screening based on age would identify 1,070, 840 infections. An estimated 552,000 patients would receive treatment with pegylated interferon and ribavirin and 229,000 would be cured of their infection. Compared to the risk-based strategy, 82,000 deaths would be averted compared to risk-based testing. The cost of this age-based screening with standard two-drug treatment was $15,700 per QALY compared with risk-based screening.

The addition of a protease inhibitor would increase the number of patients achieving a cure to 311,000, averting 121,000 deaths compared to screening based on risk. The estimated cost was $35,700 per QALY gained. The cost of this strategy was equivalent “to cervical cancer or cholesterol screening.”

The authors therefore conclude, “birth-cohort screening seems to be a reasonable strategy to identify asymptomatic cases of HCV.”


Ly KN et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med 156: 271-78, 2012.

Rein DB et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settingds. Ann Intern Med 156: 263-60, 2012.