CATIE News

• Researchers analyzed the clinical progress of Albertans diagnosed with hepatitis C
• Only 3.4% of patients were cured of hepatitis C within two years of diagnosis
• The study identified bottlenecks in the pathway from diagnosis to cure

Scientists estimate that about 1% of Canadians have been exposed to hepatitis C virus (HCV), which infects the liver and causes inflammation and injury in this vital organ. As the health of the liver degrades, complications ensue; these include severe fatigue, internal bleeding, serious abdominal infections, kidney injury, difficulty thinking clearly and liver failure. HCV infection is also associated with an increased risk for liver cancer.

In the past, treatment for HCV was based largely on regular injections of interferon-alpha. This treatment was not very effective and caused many debilitating side effects. However, in the past decade, pharmaceutical companies have developed oral regimens for HCV treatment, called direct-acting antivirals (DAA). These drugs are taken once daily for between eight and 12 weeks and are highly effective, with HCV cure rates of 95% or greater. Furthermore, DAAs are generally well tolerated.

The HCV cascade of care

There are many steps that need to be taken on the path to achieving a cure from HCV. A simplified version of the path through HCV diagnosis, care, treatment and cure is called the HCV cascade of care, and involves the following steps:

• a test for HCV antibodies – this indicates that a person was exposed to HCV
• a test for the genetic material of HCV (an RNA test) – this reveals the presence of active infection
• a test to reveal the strain, or genotype, of HCV that a person has
• referral to a provider who is experienced in the care and treatment of people with HCV
• the offer of HCV treatment followed by a prescription for treatment
• a blood test after treatment has been completed to confirm that HCV has been cured

Note that some outlines of the cascade may have fewer or more detailed stages than what is listed above.

Mapping the different steps of the HCV cascade of care is important because patients can fall out of the care cascade at different points and this reduces their chances of being diagnosed, treated and cured.

In Alberta

A team of researchers in Alberta recently published their analysis of the HCV cascade of care in their province. They found that at each step or stage of the cascade “opportunities for improvement were identified.” This assessment of the HCV cascade of care is important and points the way forward to increase opportunities for HCV testing, entry into care, retention in care, treatment and, ultimately, being cured. Hopefully, the Alberta analysis will stimulate other provinces and territories to perform updated assessments of their care cascades.

Study details

The researchers focused on participants who had a valid Alberta personal healthcare number (PHN) and who tested positive for HCV antibodies between January 2009 and December 2016.

The average profile of participants who entered the study was as follows:

• 64% men, 36% women
• 69% lived in Calgary or Edmonton
• 12% acquired HCV outside of Canada
• 21% were Indigenous
• 37% had past or current injection drug use
• 14% consumed excessive alcohol
• 9% lived in unstable housing
• 9% had a history of imprisonment
• 2% were co-infected with HIV
• 1% were co-infected with HBV
• common HCV genotypes: genotype 1 – 63%; genotype 2 – 11%; genotype 3 – 23%

Results

Flow through the cascade

The cascade began with 6,154 people who tested positive for HCV antibodies. This figure of 6,154 is equal to 100% of the group studied. Testing positive for HCV antibodies means that at some point these people were exposed to HCV; it does not reveal active infection. Therefore, further testing for the virus’ genetic material (RNA) was required. Each of the steps in the cascade were also called milestones by researchers.

HCV RNA testing

In the next step of the cascade, researchers found that 69% of participants who had HCV antibodies had their blood analysed for the virus’ genetic material. Of the people who underwent HCV RNA testing, 76% tested positive for the virus’ genetic material, which means that they have active HCV infection.

HCV genotype testing

In high-income countries, there are usually six main groupings, or genotypes, of HCV. It is important to know which genotype a person had so that the right combination of DAAs can be used. The Alberta researchers found that only 38% of participants in the study had a genotype test done.

Assessment by a doctor experienced with HCV

A total of 34% of study participants had their condition assessed by a doctor experienced with the care and treatment of HCV.

Prescription of HCV treatment

The researchers found that 12% of people in the study were prescribed DAAs.

Cure

Only about 3.4% of participants were cured of HCV infection within two years of being diagnosed.

Important findings

According to the researchers, they “identified substantial gaps in the HCV cascade of care in Alberta.” Furthermore, the research team added that “very few achieved [a cure] within two years of diagnosis [of HCV infection].”

The team also raised another important point: “We found that Indigenous people, women, people who are unstably housed and people with the lowest income were less likely to achieve cascade of care milestones.”

New infections

The study did not investigate the presence of undiagnosed HCV infection. However, the researchers stated that “if we conservatively estimate” that the number of participants in their study “represents 75% of HCV cases in Alberta, then there would be 8,389 new HCV infections during our study period, with only 8.5% being prescribed antiviral treatment.”

Bear in mind

The Alberta study is retrospective in design. It extracted health-related information collected for one purpose and re-analysed the data to get a sense of what was happening in the HCV cascade of care. It also had a relatively short time of follow-up. During the course of the study, the treatments that were available for HCV changed and access to DAAs initially was rationed based on the degree of liver injury in a person.

Despite these caveats, the Alberta study is very important. It has exposed gaps in HCV care in the province’s cascade. By identifying these gaps, the ministry of health and public health authorities can prioritize and deploy interventions to help people enter and stay in the cascade of care so that they can be cured. The Alberta study serves another function: It reminds other provinces and territories to conduct analyses of their HCV care cascades so that they can keep track of what is happening to people who test positive for antibodies to HCV.

—Sean R. Hosein

REFERENCES:

1. O'Neil CR, Buss E, Plitt S, et al. Achievement of hepatitis C cascade of care milestones: a population-level analysis in Alberta, Canada. Canadian Journal of Public Health. 2019; in press.
2. Thomas DL. Global elimination of hepatitis. New England Journal of Medicine. 2019 May 23;380(21):2041-2050.
3. Janjua NZ, Kuo M, Yu A, et al. The population level cascade of care for hepatitis C in British Columbia, Canada: The BC Hepatitis Testers Cohort (BC-HTC). EBioMedicine. 2016 Oct;12:189-195.
4. Young S, Wood E, Milloy MJ, et al. Hepatitis C cascade of care among people who inject drugs in Vancouver, Canada. Substance Abuse. 2018;39(4):461-468.
5. Høj SB, Jacka B, Minoyan N, et al. Conceptualising access in the direct-acting antiviral era: An integrated framework to inform research and practice in HCV care for people who inject drugs. International Journal of Drug Policy. 2019; in press.
6. Alimohammadi A, Holeksa J, Thiam A, et al. Real-world efficacy of direct-acting antiviral therapy for HCV infection affecting people who inject drugs delivered in a multidisciplinary setting. Open Forum Infectious Diseases. 2018 May 23;5(6):ofy120.
7. van Santen DK, van der Helm JJ, et al. Lack of decline in hepatitis C virus incidence among HIV-positive men who have sex with men during 1990-2014. Journal of Hepatology. 2017 Aug;67(2):255-262.
8. Kronfli N, Linthwaite B, Kouyoumdjian F, et al. Interventions to increase testing, linkage to care and treatment of hepatitis C virus (HCV) infection among people in prisons: A systematic review. International Journal of Drug Policy. 2018 Jul;57:95-103.
9. Chaillon A, Sun X, Cachay ER, et al. Primary incidence of Hepatitis C Virus infection among HIV-infected men who have sex with men in San Diego, 2000-2015. Open Forum Infectious Diseases. 2019 Apr 3;6(4):ofz160.
10. Nijmeijer BM, Sarrami-Forooshani R, Steba GS, et al. HIV-1 exposure and immune activation enhance sexual transmission of Hepatitis C virus by primary Langerhans cells. Journal of the International AIDS Society. 2019 Mar;22(3):e25268.