CATIE News

• B.C. researchers compared health outcomes among people with and without hepatitis C
• On average, people diagnosed with hepatitis C died about 18 years prematurely
• Curing hepatitis C reduced liver-related deaths, but not overdose-related deaths

Exposure to hepatitis C virus (HCV) can lead to this virus infecting the liver. HCV causes persistent inflammation within the liver that slowly degrades this vital organ. If undiagnosed and untreated, HCV-related inflammation results in healthy liver cells being replaced with useless scar tissue in a process called fibrosis. Over time, fibrosis injures more liver tissue. As the amount of scar tissue accumulates, the liver is less able to function and complications ensue, including severe fatigue, internal bleeding, serious abdominal infections, kidney injury and liver failure. The presence of scar tissue within the liver increases the risk for liver cancer.

A team of scientists at the British Columbia Centre for Disease Control (BCCDC) and other scientists at the University of British Columbia have been conducting extensive research with people who have HCV and others who are at high risk for this infection. The latest analysis from this research is in press in the International Journal of Drug Policy. The scientists found that people with HCV are at significantly increased risk of death compared to people who do not have HCV. Furthermore, on average, people with HCV tend to die at a much younger age than people without this virus. Many people in this study died from causes related to complications arising from injecting street drugs.

Treatment for HCV, consisting of direct-acting antivirals (DAAs), is available in Canada. In clinical trials, DAAs are highly effective, with cure rates of 95% or greater. Therefore, getting tested and treated for HCV are important steps to better liver health and overall wellbeing. However, curing people of HCV does not mean that the issues underpinning their use of injection street drugs are somehow gone. Curing HCV should be seen as merely one of several steps that aim to improve the overall health and resiliency of vulnerable populations.

Study details

The team of scientists has been involved in a long-term study called the BC Hepatitis Testers Cohort. This study has collected health-related information from 1.3 million people who have undergone testing for HCV, hepatitis B virus and HIV since 1992. Scientists affiliated with the study are able to access several databases to link each participant in the study to information about medical visits, hospitalizations, prescriptions for medicines, cases of cancer and deaths.

For the present analysis, researchers focused mainly on data collected from people who had a test for HCV antibodies or a test for the genetic material of HCV (RNA) between April 1992 and December 2015. The scientists continued to collect information to the end of 2018, including information on any deaths that took place among participants.

The team classified people into two HCV infection categories, as follows:

• existing HCV infections – people whose first HCV test in the study was positive
• new HCV infections – people who had previously tested HCV negative one or more times in the study but subsequently tested positive

The team grouped the deaths that occurred as follows:

• liver related – including from symptoms of severe liver injury (cirrhosis), liver cancer, other complications of HCV and hepatitis-causing viruses, as well as liver disease related to alcohol or other causes
• acquisition related – including from injection drug use, HIV-related causes and all other causes of death

The scientists divided the study population into the following main groups:

• HCV positive – 5.3%
• HCV negative – 94.7%

Results

As of December 31, 2018, the distribution of deaths in the two main groups was as follows:

• HCV-positive people – 28% died
• HCV-negative people – 10% died

This difference meant that HCV-positive people had a nearly three-fold increased risk of death compared to HCV-negative people.

Age at death

On average, the age at which people in each of the main groups died was as follows:

• HCV-positive people – 56.4 years
• HCV-negative people – 75.5 years

Thus, many HCV-positive people died almost 20 years prematurely.

HCV-positive people who died were likely to have the following features:

• male
• a history of injecting street drugs
• problematic use of alcohol
• co-infected with HIV
• a great degree of material and social deprivation

HCV-negative people were more likely to die from age-related causes, such as cancers affecting organ-systems other than the liver and cardiovascular disease, compared to HCV-positive people.

HCV treatment

The scientists found that there were 16,821 people in the study who tested positive for HCV RNA and who received DAAs. Overall, they found that participants who took treatment and who were cured of HCV had only slightly reduced survival compared to HCV-negative people. People who took HCV treatment but who were not cured were much less likely to survive than people who were cured. The scientists suggested that this poor survival was likely because most of the people whose treatment failed “had late-stage liver disease, which was more difficult to cure, and other underlying co-morbidities associated with high mortality.”

Changes in death rates

After adjusting their calculations for a person’s age, the scientists found the following trends in the following groups:

Liver-related deaths

• 1992–2002 – increasing rates of death
• 2002–2009 – stable rates of death
• 2014–2018 – a “sharp decline” that coincided with the availability of DAAs

Injection-related deaths

• 1992–2000 – increasing rates of death
• 2001–2013 – gradually declining rates of death
• 2014–2018 – a dramatic increase in rates of death (the scientists noted that this increase coincided with “the increase in fentanyl and fentanyl-analogue-related overdose deaths”)

The scientists stated that people who were HCV negative and who injected street drugs had a dramatically increased risk of death starting in 2004.

Recognizing related issues

The B.C. scientists expect that more HCV-positive people will be cured in the years ahead as that province rolls out testing and treatment efforts. As a result, deaths from HCV-related liver disease are expected to decrease. However, the scientists noted that a study in the U.S. has found that deaths from severe liver injury arising from excess intake of alcohol are increasing, particularly among people aged 25 to 34 years with HCV. It is possible that alcohol-related liver disease could become more of an issue in the future in people with HCV in Canada. A recent study by scientists in France has found that excess alcohol (in addition to tobacco and body weight) were issues that affected the health of people with HCV and HIV. A study from Australia found that while deaths due to HCV-related liver disease are declining in the current era, liver problems are on the rise due to excess alcohol intake.

Another major issue is the increase in deaths related to opioid overdoses that is currently underway in North America. According to the scientists, B.C. is disproportionally affected by this crisis, as are males who inject drugs. They further stated that 80% of fentanyl overdoses that occurred in B.C. between 2014 and 2018 were in men.

Moving forward

The current BCCDC study is an important one, as it shows that much work is needed to help people who are at risk for HCV, who have HCV or who have been cured of HCV. Public health and other authorities need to enhance efforts to address issues that underpin a person’s initiation of injection drug use.

Interventions could include at least the following:

• enhanced harm reduction services
• opioid substitution therapy
• low-barrier access to a range of mental health services to deal with the emotional and psychological injury that arises from trauma faced by many people who inject street drugs

Vulnerable young people need psychological support so that they do not turn to and become dependent on substances. There are likely additional interventions that can be deployed to help populations affected by HCV (and the opioid overdose crisis). This crisis is an opportunity to help work with Canada’s vulnerable communities and make them safer and stronger.

Resources

Opioids – Health Canada

Hepatitis C – CATIE

—Sean R. Hosein

REFERENCES:

1. Krajden M, Cook DA, Wong S, et al. What is killing people with hepatitis C virus infection? Analysis of a population-based cohort in Canada. International Journal of Drug Policy. 2019; in press.
2. Alavi M, Law MG, Valerio H, et al. Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia. Journal of Hepatology. 2019; in press.
3. Picard A. Opioid Crisis: Listen to the big city mayors. The Globe and Mail. 29 May 2017. Available at: https://www.theglobeandmail.com/opinion/opioid-crisis-listen-to-the-big-city-mayors/article35146407/
4. Picard A. Where is Canada’s plan to eliminate hepatitis C? The Globe and Mail. 9 July 2019. Subscription required.
5. Santos ME, Protopopescu C, Sogni P, et al. HCV-related mortality among HIV/HCV co-infected patients: The importance of behaviours in the HCV cure era (ANR CO13 HEPAVIH Cohort). AIDS and Behavior. 2019; in press.
6. Innes H, McAuley A, Alavi M, et al. The contribution of health risk behaviors to excess mortality in American adults with chronic hepatitis C: A population cohort-study. Hepatology. 2018 Jan;67(1):97-107.
7. Irvin R, Chander G, Falade-Nwulia O, et al. Overlapping epidemics of alcohol and illicit drug use among HCV-infected persons who inject drugs. Addictive Behaviours. 2019 Sep;96:56-61.