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  • Scientists in B.C. mapped the flow of patients from hepatitis C diagnosis to cure
  • At each stage of the cascade, some patients did not progress to the next step towards cure
  • Out of patients who had completed genotype testing, only 61% started treatment

Exposure to hepatitis C virus (HCV) can lead to this virus infecting the liver. Chronic HCV infection causes persistent inflammation within the liver that slowly degrades this vital organ. If HCV is undiagnosed and untreated, the liver becomes chronically inflamed. In turn, chronic inflammation causes healthy liver cells to be replaced with useless scar tissue in a process called fibrosis. 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.

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Treatment then and now

Treatment for chronic HCV infection once consisted of regular injections of interferon-alpha for between 24 and 48 weeks. This treatment was modestly effective at curing HCV, but it came at the cost of highly unpleasant side effects. However, over the past six years in Canada and other high-income countries, all-oral medicines gradually became available for HCV treatment. These medicines, called direct-acting antivirals (DAA), have revolutionized HCV treatment due to their potency, with cure rates of 95% or greater. In some cases, people can be cured after eight consecutive weeks of treatment. DAAs are generally well tolerated.

About the cascade of care

Scientists who study health systems refer to the flow of people with HCV infection through the process of diagnosis, care and treatment as “the cascade of care,” “the cascade of HCV care” or, simply, “the cascade.” Analysing the cascade of HCV care is important because it can help to identify barriers to care and whether people are receiving care and treatment in a timely manner.

A team of scientists at the British Columbia Centre for Disease Control (BCCDC) and the University of British Columbia collaborated on a study to analyse the cascade of HCV care in that province. In an article to be published in the medical journal Liver International, the scientists report that while progress in the diagnosis and treatment of HCV has been made in recent years, gaps in the cascade still exist. The largest gap they identified was in the initiation of HCV treatment. The scientists suggested solutions to decrease the size of this and other gaps in the cascade.

Study details

The scientists accessed several databases for their work. In particular, they used health-related information collected from the BC Hepatitis Testers Cohort. The scientists stated that this cohort includes all people in the province who “ever tested for HCV or HIV, or were diagnosed with hepatitis B virus (HBV), HCV, HIV or active TB in B.C. between 1990 and 2015, linked with data on medical visits, hospitalizations, cancers, prescription drugs and deaths. The laboratory testing, prescription and mortality data was updated up to December 31, 2018.”

These data were used to estimate the flow of people moving through the following different steps of the cascade:

  • tested for HCV antibodies (this can tell if a person has been exposed to the virus)
  • tested for current (active) HCV infection – RNA testing
  • found RNA positive; confirmed current HCV infection
  • the strain (genotype) of HCV was assessed
  • initiated treatment
  • cured

Results

Tested for HCV antibodies

The scientists estimated that there were about 61,127 people who have been exposed to HCV in B.C. Of these people, 87% (53,441) had been diagnosed with exposure to HCV. The presence of the antibody only reveals that a person has been exposed to the virus; it cannot indicate how long ago such exposure occurred or if the infection is active.

Testing for current HCV infection

To find out if HCV is currently causing infection, people can have a sample of their blood tested for the presence of HCV’s genetic material (RNA). Out of 53,441 people who had tested positive for HCV antibodies, 83% (44,507) had their blood samples undergo RNA testing. Of these people, 72% (32,031) tested positive for HCV RNA—they had active HCV infection.

Genotyping

Historically, identifying the strain, or genotype, of HCV that a person had was an important factor in determining which regimen they received because some genotypes did not respond well to interferon and first-generation DAAs. Today, healthcare providers and patients can choose from several regimens that are effective for all strains of HCV, so genotyping is not as important. Genotyping may still have a place for scientists monitoring trends in virology (that is, which strains are currently common and whether new strains are entering a city or region). Of the 32,031 people with current HCV infection, 90% (28,716) had their virus genotyped.

Initiation of treatment

Of the 28,716 people whose HCV was genotyped, 61% (17,441) initiated HCV treatment.

Cured

Of the 17,441 people who initiated treatment, 90% (15,672) were subsequently cured of HCV.

Bridging the gaps

The scientists made it clear that while much progress has been made in recent years with the HCV cascade of care, gaps still remain with RNA testing, particularly among people whom they describe as having “historical risk factors.” This term encompasses people who used to inject street drugs but no longer do so. The scientists stated that “this group of people may be difficult to re-engage in HCV-related care, particularly if they are ‘hardly reached’ by other health care services.” One potential strategy to help minimize interruptions in the cascade is to use what the scientists called “reflex testing,” which refers to automatically testing blood samples that test positive for HCV antibodies for RNA. This prevents the need for people having to return to a clinic for RNA testing. The scientists stated that reflex testing is being pilot tested in B.C.

Another possible solution to streamlining the path to treatment is to do away with the need for genotype testing. The scientists suggested that the availability of “new pan-genotypic DAA regimens may remove the need for HCV genotype testing prior to treatment initiation,” particularly for people with the following profile:

  • have not previously been treated for HCV
  • do not have serious liver injury (cirrhosis)

Focus on specific populations

The B.C. scientists stated that “additional strategies to enhance treatment uptake among people who currently or previously inject drugs, particularly younger people and those who live in more materially deprived areas, should be explored. The 2018 cascade suggests that these groups have lower treatment uptake, compared to the overall cohort.”

The scientists advanced the following additional steps that could be taken to help remove gaps in the cascade of HCV care:

  • broadening the DAA prescriber base to include general practitioners and addiction medicine specialists
  • providing or enhancing peer support and patient navigation services
  • having HCV treatment services in the same locations as community-based facilities used by people who inject drugs (such as harm reduction centres, supervised injection sites, opioid substitution clinics, places that provide services for street-involved people)

Bear in mind

Like all studies, the present analysis was imperfect. However, by integrating health-related information from several databases, the scientists were able to get a good assessment of the state of the HCV care cascade in B.C. The scientists stated that their analysis could be used to refine “programs and policies in B.C. to optimize the HCV response within the context of a vastly changed treatment landscape.”

The World Health Organization has set targets so that the elimination of HCV as a public health threat can be achieved by the year 2030. The scientists stated:

“To achieve viral hepatitis elimination goals, B.C. needs to work across multiple levels of the healthcare system to define the supports required to link into care those who remain unassessed, expand capacity to assess and treat in a variety of settings, and ensure appropriate access to harm reduction services to prevent new HCV infections or re-infection after treatment.”

The present analysis of the HCV cascade of care in B.C. has an important role to play in helping this province move forward in curing more people of this virus.

Resources

FDA—Rare cases of liver injury with some hepatitis C treatmentsCATIE News

Trends in deaths among people with hepatitis C virus in British ColumbiaCATIE News

The cascade of hepatitis C virus care in AlbertaCATIE News

Hepatitis CCATIE

—Sean R. Hosein

REFERENCES:

  1. Bartlett SR, Yu A, Chapinal N, et al. The population level care cascade for hepatitis C in British Columbia, Canada as of 2018: Impact of direct acting antivirals. Liver International. 2019; in press.
  2. Sokol R, Fisher E. Peer support for the hardly reached: A systematic review. American Journal of Public Health. 2016 Jul;106(7):e1-8.