Direct-Acting Antiviral Agents (DAA): The New Era of Hepatitis C Treatment in Malaysia (Frequently Asked Questions) – Dr Chieng Jin Yu

What is Hepatitis C infection?

Hepatitis C is a liver infection caused by the Hepatitis C virus (HCV). In Malaysia, an estimated 2.5% of the adult population is positive for HCV, with 59% of cases transmitted through injection methods.1

 

Can a patient with Hepatitis C infection be recognised through his/her appearance?

No, HCV infection cannot be identified through a person’s appearance, especially in the early phase.

What are the typical symptoms of Hepatitis C infection?

Hepatitis C can range from a mild illness lasting a few weeks to a serious, lifelong illness. Approximately 80% of people infected by HCV will develop a chronic infection. Out of the chronically infected population, about 10% to 20% eventually develop cirrhosis (scarring of the liver) over 20 years. If left untreated, chronic hepatitis C can cause serious health problems and even death as a result of liver failure or liver cancer.

How does Hepatitis C spread?

Today, most people become infected with HCV by sharing needles or injecting drugs. A person can also contract HCV through sexual contact with an infected person. Before 1992, Hepatitis C was also commonly spread through blood transfusions and organ transplants.

How is Hepatitis C diagnosed?

If HCV antibodies (Anti-HCV) are detected in a blood test, it means the person was exposed to the virus at some point. HCV RNA (or PCR) test should be done to see whether the person is still actively infected.

At least seven varieties have been identified in HCV infection worldwide. The predominant genotypes in Malaysia are Genotype 3 (~60%) and 1 (~35%). Genotype 3 is believed to be associated with more severe liver disease and poorer response to Direct-Acting Antiviral Agents (DAAs) compared to other HCV genotypes.

How is Hepatitis C treated?

HCV was typically treated with once-weekly injections of pegylated-interferon alpha plus twice a day dose of oral ribavirin (RBV) for 24 weeks or 48 weeks. This combination achieved sustained virological response (SVR) of 50-60%; undetectable or unquantifiable HCV RNA for 12 weeks or longer after treatment completion, which is consistent with cure of hepatitis. However, quite a significant number of patients had to stop treatment as they could not tolerate the adverse effects such as hemolytic anemia, thrombocytopenia, flu-like symptoms, and psychiatric disturbances.

So where do DAAs come in?

The development of DAAs, with very high cure rates (90-100%), has revolutionised HCV treatment. The HCV treatment guidance from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommends that all patients with chronic HCV infection be initiated on DAAs. Sadly this does not include those with limited life expectancy in which the course of disease cannot be remediated by pharmacological treatment or a liver transplant.

DAA regimes were not commonly prescribed in Malaysia as they cost up to RM300,000 per course of treatment. In 2017, the Ministry of Health (MOH) started importing the generic version of Sofosbuvir and was able to implement free HCV treatment with DAA regime in eleven government hospitals. This was further expanded to eighteen hospitals in 2018. The MOH aims to eradicate and eliminate HCV by 2030.

What is the available DAA regime in Malaysian government hospitals?

Combination therapy Daclatasvir 60 mg and Sofosbuvir 400 mg (DCV/SOF) is a once-daily oral DAA regime. Sofosbuvir is a potent pangenotypic NS5B RNA polymerase inhibitor with a high barrier to resistance. It can be used in those with kidney function eGFR >30ml/min/1.73m2. Daclatasvir exhibits its action by binding to the NS5A protein, consequently inhibiting RNA viral replication and viral assembly. Headache, nausea and fatigue are the most commonly reported adverse effects (10%).

Sometimes, ribavirin is used together with DCV/SOF, with the dose of 1000mg/day for those with body weight <75kg, and 1200mg/day for those ≥75kg. The common adverse effects of ribavirin are anaemia, flu like symptom, headache, fatigue and psychiatric disturbance.

DCV/SOF for 12 weeks is recommended in treatment-naïve non-cirrhotic patients; with or without RBV in those with compensated cirrhosis for 24 weeks; and with RBV for 12 weeks or 24 weeks without RBV if ineligible decompensated cirrhosis or after transplant.

By achieving SVR, the risks of liver failure, liver cancer and even non-liver related mortalities can be reduced. The DCV/SOF regime is reported to achieve SVR at 90% or more.

Is there a HCV vaccine available?

Unfortunately, there aren’t any vaccines against HCV for now. Research is ongoing, but HCV is highly variable among strains and rapidly mutating which makes producing an effective vaccine very difficult.

What should I do if I am at risk of HCV infection?

Contact your doctor to obtain a specific blood test to confirm the diagnosis, investigate for any liver damage, and to find out if you can be started on treatment. Hepatitis C can be cured in most cases, especially as DAA therapy becomes more accessible to patients with HCV in Malaysia. You will also need to learn how to take care of your liver and avoid spreading HCV to others.

Reference:

  1. Ruksana Raihan. Hepatitis in Malaysia: Past, Present, and Future. Euroasian J Hepatogastroenterol. 2016 Jan-Jun; 6(1): 52–55.

By Dr Chieng Jin Yu, Medical Lecturer, Consultant Gastroenterologist and Hepatologist, Universiti Putra Malaysia (UPM).

[This article belongs to The Malaysian Medical Gazette. Any republication (online or offline) without written permission from The Malaysian Medical Gazette is prohibited.]

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