Eliminating hepatitis C: Still some way to go, so what needs to change?

In 2016, WHO proposed eliminating hepatitis C as a public health threat by 2030, targeting an 80 per cent reduction in new chronic infections and a 65 per cent reduction in mortality from 2015 levels. In 2021, WHO revised the goals to include new targets of 80 per cent of eligible people to receive treatment and 80 per cent of total infected people to be diagnosed.

Only 14 countries are on target to reach these goals by 2030. New Zealand is well short of all targets at current rates of treatment.

There has been exceptional progress with the tools required to eliminate hepatitis C – excellent diagnostic tests and highly effective treatment – but the reality is there is a long way to go. The current diagnostic strategy is to screen with a hepatitis C virus (HCV) antibody test then confirm with a PCR test. This stepwise process introduces significant delays before treatment can be started. Many patients fail to return for follow-up at some point.

There is now highly effective treatment that is fully subsidised. Glecaprevir and pibrentasvir (Maviret) is a combined drug pill that is 98 to 99 per cent effective after an eight-week course (equally effective for all genotypes; therefore, testing for genotype or viral load is not required).

Drug interactions with Maviret are minimal but need to be checked via the New Zealand Formulary interactions checker (nzf.org.nz) or the University of Liverpool Hep Drug Interactions website (hep-druginteractions.org).

The combination is very well tolerated compared with Viekira Pak (previously funded but not suitable for all patients), which had significant side effects, mainly related to the ribavirin component.

Some assessment is still required to check for cirrhosis, for two reasons: Maviret may be contraindicated, and a longer treatment course may be required. Ideally, all patients should have a FibroScan – an accurate non-invasive test for fibrosis and cirrhosis. An aspartate aminotransferase-to-platelet ratio index (APRI) is a less accurate but useful score if the patient is considered low risk. APRI calculators can be found online and require only an AST level and a platelet count.

A PCR test should be checked 12 weeks after completing treatment. Annual HCV RNA assays or HCV core antigen assays are recommended for patients with ongoing risk factors (eg, people who inject drugs [PWID]) as previous infection does not confer immunity. The 1 to 2 per cent of people who are treatment failures require different treatment at specialist clinics. Some funding issues for retreatment have yet to be resolved.

It is estimated approximately 35 to 40 per cent of New Zealanders with chronic hepatitis C virus infection are undiagnosed

This is all good news, but there are two big problems: diagnosing all the infected individuals in New Zealand, and encouraging all infected people to be treated.

HCV infection is usually acquired as an adult, and chronic infection is the most common outcome of acute infection (which is usually asymptomatic).

It is estimated approximately 35 to 40 per cent of New Zealanders with chronic HCV infection are undiagnosed because of a lack of awareness of previous risk of exposure and lack of symptoms. Based on population screening, there were 45,000 to 50,000 individuals in New Zealand with chronic hepatitis C in 2015.

The treatment numbers are low. Modest numbers were treated with Viekira Pak, and only just over 5000 have started Maviret since this treatment was fully funded in 2019 – this brings the number still infected and needing treatment down to approximately 40,000 in 2022. Overall, only 20 per cent of the original cohort have been treated to date.

After an initial spike in treatment in 2019, low numbers of patients have been treated with Maviret over the last two years – the decline actually happened before the COVID-19 pandemic, although this has not helped. Currently, only 50 cases per month are starting treatment – well short of the target of 2200 people per year who need to be treated to achieve WHO targets.

Hepatitis C is responsible for more than 200 deaths per annum and is now the leading indication for liver transplantation in New Zealand. The incidence of hepatitis C-related hepatocellular carcinoma (HCC) remains at 80 to 90 cases per year. The rate of HCC looks likely to increase in New Zealand but may fall after 2030.

New infections are decreasing globally, although there are major differences between countries. The prevalence of hepatitis C is also gradually decreasing – some countries, such as Egypt, have made remarkable progress in treating the majority of its infected people.

Remarkably, the incidence of hepatitis C is likely to continue to increase in the USA because of lack of harmreduction strategies and the opioid (fentanyl) epidemic.

Currently, the main strategy is opportunistic screening based on risk factors.

Testing all patients with unexplained elevation of alanine aminotransferase beyond three months is essential. Anyone with a history of intravenous drug use, even if they have normal liver function tests, needs to have an HCV antibody test then confirmatory PCR test. Screening of the general population (average risk) will find one case in 100–200 individuals, but 50 to 80 per cent of PWID are infected.

Active case finding is starting within prisons and drug dependency clinics. A laboratory look-back programme has identified many thousands of New Zealanders with chronic HCV infection who have no record of treatment.

Almost all new HCV infections are in PWID. Prevention can be very successful by improving access for PWID to needle and syringe exchange programmes, opioid substitution treatment and community rehabilitation programmes. Identifying infected individuals within this population will rapidly reduce new infections. Reinfections do occur in the PWID population, but this problem can obviously be diminished by reducing the pool of infected PWID.

Current testing and treatment strategies are not going to achieve the WHO targets and are simply not good enough. There needs to be a wider testing programme and a national registry. Primary care continues to have an important role in performing opportunistic screening. However, the key target groups are not being reached.

Increasingly, it is clear that community clinics closely associated with needle exchange programmes are more likely to attract a vulnerable and disengaged population. Community clinics need to establish trust with the PWID population, and this includes peer workers and nurses who can gain confidence in those who attend and explain the need for testing and treatment. Peer workers who have completed treatment greatly encourage compliance.

The current model of diagnosis and treatment has too many inherent delays and potential for loss of follow-up at each step. Home-based antibody testing (pinprick or buccal swab) has been shown to be better than laboratory venipuncture testing. However, the future will be point-of-care (first contact) rapid diagnosis, ideally with a rapid PCR test so treatment can be initiated at the first visit.

The current uptake of testing in prison is low. Point-of-care PCR testing in prisons has, in other countries, led to dramatic increases in uptake and initiation of treatment.

Point-of-care PCR testing will be possible in the near future. PCR machines that are no longer needed for COVID-19 PCR testing could be used (Cepheid GeneXpert machines). Australia is leading the way by setting up 85 community sites to test 50,000 to 60,000 people (2021 to 2024) at opioid substitution clinics, prisons, mental health services, homelessness services and Aboriginal health organisations.

Increasing access to FibroScans at community clinics does improve efficiency in the treatment pathway. Those patients identified with cirrhosis can be treated appropriately or referred to secondary care clinics. They can also be identified as requiring long-term surveillance for HCC. Individuals aged under 35 have a very low risk of cirrhosis and could be treated without further assessment.

Treatment prescribing needs to be widened to include nurses and pharmacists, otherwise many people are lost to follow-up after referral to GPs. Several different models of care have already been initiated in New Zealand with early signs of success.

There are many current barriers to getting diagnosed and treated (stigma, mental health, homelessness). Some more innovative approaches are required. Peer-led point-of-care testing and early initiation of treatment has been shown to be successful, and this model needs to be rapidly adopted across the country.

Alan Fraser is a gastroenterologist with Auckland Gastroenterology, Mercy Endoscopy and Endoscopy Auckland, and associate professor of medicine at the University of Auckland