- A B.C. study measured the effect of direct-acting antiviral (DAA) treatments on death rates
- Curing hepatitis C with DAAs was linked significantly with a lower risk of death from all causes
- This included a lower risk of drug-related death, illustrating the benefits of service integration
Direct-acting antivirals (DAAs) are highly effective, safe and curative treatments for hepatitis C. The emergence of DAAs has altered the course of hepatitis C treatment efforts, showing promise for improving outcomes for those living with the infection and making the elimination of hepatitis C as a public health threat a reality. While research has shown the effectiveness of DAAs on reducing the risk of death and liver cancer for people in clinical studies, less is known about the health impact of the rollout of DAAs at the population level.
Study details
Researchers from the British Columbia Centre for Disease Control (BCCDC) looked at the effect of DAAs on the risk for different causes of death for people with chronic hepatitis C. Their study is the first to assess the effects of DAAs on types of death with a specific cause (i.e., death from liver- and drug-related causes) using a population-based cohort. Notably, past studies have not explored the impact of DAAs on deaths from drug-related causes, something that the researchers note is of critical relevance for people with hepatitis C in Canada and other countries experiencing an ongoing and worsening drug poisoning and overdose crisis.
The study draws from a large population-based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort (BC-HTC) is a large data set that draws from a variety of clinical, case, testing and administrative sources. The data set captures more than 95% of the hepatitis C testing performed in the province through the public health laboratory, as well as all hepatitis C treatments and deaths that are recorded in centralized systems. The BC-HTC has been collecting data since 1990 and includes approximately 1.7 million people.
Using this data set, the researchers examined 10,855 people who were treated with DAAs, as well as 10,855 untreated people who were matched with the treated group on the basis of their date of hepatitis C diagnosis as well as other relevant factors including sex, age, cirrhosis and other health conditions. Of those who were treated, 10,426 or approximately 96% were cured and 425 were not cured.
The researchers compared death rates among three groups:
- people who were treated with DAAs and were cured (had a sustained virological response, or SVR)
- people who were treated with DAAs and were not cured (did not have an SVR)
- people who did not receive treatment
Results
The study revealed significant decreases in the risk of death from all causes, as well as in the risk of death from liver-related causes and drug-related causes, for people who were cured of hepatitis C with DAAs.
When comparing individuals who were cured with DAAs to those who hadn’t received treatment, the researchers found:
- 81% reduction in risk of death from all causes
- 78% reduction in risk of death from liver-related causes
- 74% reduction in risk of death from drug-related causes
The researchers also explored factors that were linked to having a higher risk of death from specific causes:
- Death from liver-related causes: Factors associated with a higher risk of death from liver-related causes included cirrhosis and older age (40 years of age or more).
- Death from drug-related causes: The use of injection drugs was the strongest factor linked to death from drug-related causes. Other factors included being younger, engaging in problematic alcohol use and having an HIV and/or hepatitis B co-infection.
Implications for the future
The findings of this study are promising – they show that having access to DAA treatments and being cured can significantly reduce the overall and cause-specific risks of death for people with hepatitis C. These findings are particularly relevant for two priority groups in Canada, in whom the prevalence and incidence of hepatitis C infections are much higher.
Older adults and people with cirrhosis have a higher risk of death from liver-related causes
Hepatitis C is a virus that injures the liver over time. It can live in the body for decades without a person having symptoms or feeling sick. Over time, injury to the liver can lead to cirrhosis, liver failure and cancer. The burden of illness for hepatitis C in Canada is linked to deaths from liver-related causes.
In Canada, there is a high prevalence of hepatitis C infections among people born between 1945 and 1975, who make up an estimated 66%–75% of people living with hepatitis C nationally. This group most likely acquired infection years ago and is now being diagnosed with serious illnesses affecting the liver, such as cirrhosis, liver failure or cancer.
The researchers in this study have shown that curing hepatitis C with DAAs is associated with a reduction in the risk of death from all causes, including liver-related causes. However, the reduction in the risk of death from liver-related causes was smaller among people who were over the age of 40 and among people who had developed cirrhosis. This indicates that there is an urgent need to further scale up testing and treatment for people in this age cohort before cirrhosis can develop, to optimize the benefits of cure from DAAs.
People who inject drugs have a higher risk of death from drug-related causes
The majority of new hepatitis C infections in Canada occur among people who inject drugs. Hepatitis C is not the only challenge faced by this population – the risks associated with injection drug use for bloodborne infections (including hepatitis C and HIV) overlap with and are made worse by the ongoing drug poisoning and overdose crisis in Canada. In contrast to older adults who may have lived with hepatitis C for a long time, young people who inject drugs are more likely to die from drug-related causes than liver-related causes. As noted by the researchers, the impact of DAAs on deaths from drug-related causes has never been studied. Younger age, injection drug use and problematic alcohol use were associated with higher risk of death from drug-related causes. On a positive note, study findings showed that being treated and cured of hepatitis C was associated with reduced risk of death from drug-related causes. This indicates the importance of service integration for people who use drugs including harm reduction, addiction treatment, hepatitis C care and social support services to improve the overall well-being and survival of people who use drugs.
Information about the benefits of cure from DAAs can be used to improve outcomes for people who use drugs. The researchers note that further studies are needed to better understand the factors that contribute to this reduction in risk for death from drug-related causes, so that they may be better used to improve outcomes for people who use drugs and to optimize the benefits of being cured of hepatitis C. Further, current hepatitis C elimination goals are measured and monitored by using set targets. This includes monitoring decreases in liver-related deaths for people with hepatitis C. As the findings of this study suggest that DAAs may also decrease death from other causes, additional targets should be added to monitor improvements in this area and any future hepatitis C elimination goals.
—Shannon Elliot
Resources
The British Columbia Hepatitis Testers Cohort
Blueprint to Inform Hepatitis C Elimination Efforts in Canada
REFERENCES:
- Janjua NZ, Wong S, Abdia Y, et al. Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study. Journal of Hepatology. 2021 Nov;75(5):1049-1057.
- Samji H, Yu A, Wong S, et al. Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada. International Journal of Drug Policy. 2020 Oct 19;86:102989.
- Bartlett SR, Wong S, Yu A, et al. The impact of current opioid agonist therapy on hepatitis C virus treatment initiation among people who use drugs from in the DAA era: A population-based study. Clinical Infectious Diseases. 2021; in press.