Introduction
Hepatitis C virus (HCV) infection is a major public health challenge for Australia. Acute infection progresses to chronic disease in up to 75% of cases, and these people are at risk of progressive liver fibrosis leading to cirrhosis, liver failure and hepatocellular carcinoma (HCC). Around 20%–30% of people with chronic HCV infection will develop cirrhosis, generally after 20–30 years of infection.
The problem
Despite one of the highest HCV diagnosis rates in the world, treatment uptake in Australia remains low (2000–4000 people/year, or 1%–2% of the infected population). The introduction of new direct-acting antiviral agents (DAA) regimens is a major advance for HCV therapy. Their high efficacy, short duration and excellent tolerability mean that most people will now be suitable for treatment and that most people who start treatment will be cured. The PBS listing allows the new HCV medicines to be prescribed by gastroenterologists, hepatologists or infectious diseases physicians who are experienced in treating chronic HCV infection, as well as GPs who are eligible to prescribe under the PBS in consultation with one of these specialists.
Pre-referral work up
Current HCV infection should be confirmed by a polymerase chain reaction (PCR) assay for HCV RNA. Approximately 25% of acute HCV infections will clear spontaneously within 6 months; these individuals continue to be HCV antibody- positive but do not have detectable HCV RNA in plasma. Criteria for PBS eligibility require evidence of chronic infection documented by repeated HCV antibody positivity and HCV RNA positivity. There are seven different HCV genotypes (1–7). The common genotypes in Australia are genotype 1 (50%–55%) and genotype 3 (35%–40%). As approved treatment regimens for HCV infection are genotype-specific, HCV genotyping is necessary before treatment initiation.
Direct-acting antiviral agents
Direct-acting antiviral agents that target multiple steps in the HCV replication life cycle have been developed and are highly effective, safe and require a short treatment duration. Virtually all patients are suitable for direct-acting antiviral therapy, including those previously intolerant of or ineligible for interferon therapy. The approved direct-acting antiviral agents are: sofosbuvir (Sovaldi), ledipasvir/sofosbuvir (Harvoni) and daclatasvir (Daklinza) and can successfully cure hepatitis C in over 90 per cent of cases. Treatment can take as little as 8-12 weeks, without many of the serious side-effects associated with older, interferon based regimens.
Genotype 1
Sofosbuvir plus ledipasvir is a coformulated, once-daily, single-pill regimen. The recommended treatment duration is 12 weeks. Rates of cure are ≥ 95%.
Sofosbuvir plus daclatasvir therapy is recommended for 12 weeks in people with no cirrhosis who are treatment-naïve. Rates of cure are ≥ 95%.
Genotype 2
The interferon-free treatment is sofosbuvir plus ribavirin for 12 weeks with a rate of cure ≥ 90%.
Genotype 3
Genotype 3 HCV is harder to cure using direct-acting antiviral therapy, particularly in people with cirrhosis and prior non-responders to pegylated interferon plus ribavirin. The interferon-free treatment regimens available include sofosbuvir plus daclatasvir for 12 or 24 weeks, and sofosbuvir plus ribavirin for 24 weeks. Rates of cure ≥ 85%.
Genotypes 4-6
The treatment regimen available is the combination of sofosbuvir plus pegylated interferon and ribavirin for 12 weeks. There are no interferon free regimes available at this time, but they may come in the near future. Rates of cure ≥ 90%.
Summary
The above information is just a brief summary of the major new treatment options with complexity added to the regimes due to previous treatment with interferon based treatments and the degree of liver damage. From a general practice perspective, the new treatments options have low side effects, shorter duration of treatment and high cure rates, meaning that all Australians living with HCV should be referred to specialists with an interest in liver disease patients for assessment and treatment.
References:
Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis C virus infection: a consensus statement 2016. Melbourne: Gastroenterological Society of Australia, 2016.
AUTHOR | Dr Anthony Rode
Dr Anthony Rode (MBBS Hons, PhD, FRACGP) graduated with Honours from the University of Melbourne and completed a hepatology PhD through the Dept of Medicine at The Royal Melbourne Hospital. He has published gut and liver disease research internationally and has extensive experience in treating Hepatitis C through working in public chronic liver disease and hepatitis clinics. He is the co-founder of Melbourne GI and Endoscopy.
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