HCV Drug Treatment - New Frontiers

What is Hepatitis C Virus (HCV) Infection?

Hepatitis C is an inflammation of the liver caused by a virus. It is primarily spread through blood and blood products, infected needles and from a pregnant mother to baby. Hepatitis C virus (HCV) can result in acute and consequently long-term infection of the liver.

While some of the symptoms include fever, fatigue, nausea, loss of appetite, abdominal pain or jaundice-like condition, HCV is often asymptomatic and can go undetected. When left undiagnosed or untreated for a long time, HCV can lead to chronic liver disease (CLD) or hepatocellular carcinoma (liver cancer).

Traditional HCV Treatment

Traditionally, HCV was treated with a combination of weekly pegylated interferon injections and ribavirin tablets (twice daily) for a period of anywhere between 6 and 12 months. However, traditional interferon therapy does not work for every patient and the virus often resurfaces within 12-24 months. Besides being expensive (3-6 lakhs for the course of treatment), pegylated interferon with ribavirin combination has serious side effects often causing bone marrow depression, resulting in severe anemia and lowering of white blood cells and platelets. Patients often experience cardiac complications like palpitations and breathlessness.

Peg interferon is also used in the treatment of Hepatitis B (HBV) and HIV infection, which means it is not specific to HCV. Since it is used for multiple infections, there is a risk that the HCV virus may become resistant to the drug.

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Latest in Line Drugs for HCV Treatment in India

The introduction of the new drug molecule Sofosbuvir by Gilead Pharma in early 2014 (US and EU markets) was a game changer in HCV treatment. Sofosbuvir is the drug used for all genotypes of HCV from 1 to 6. This is a targeted drug (direct acting agent – DAA) that works by blocking the polymerase enzyme, which the virus uses to reproduce. Sofosbuvir not only kills the virus effectively but also blocks its reproduction. In 2015, Gilead entered into agreement with a number of companies in India to sub-license the production of generic sofosbuvir, which was made available to the Indian markets in March 2015.

Till February 2016, sofosbuvir (400mg a day) was being used in combination with ribavirin (twice daily) for genotype 2 and 3, and with peg interferon + ribavirin combination for genotype 1 and 4. Genotype 2 and 3 are fairly easy to treat while genotype 1 and 4 are the hardest. The treatment was hard for most patients as using ribavirin again meant blood-related side effects like anemia, leukopenia (lowering of white blood cells) and thrombocytopenia (lowering of platelets). Often, patients with chronic liver disease experienced bleeding from the digestive tract. Ribavirin is also not an option for those with bleeding disorders like hemophilia.

The entry of other drugs to be used with sofosbuvir in February 2016 has proven to be another big landmark in HCV treatment and totally eliminating the need for peg interferon and ribavirin. These drugs include ledipasvir, telaprevir and daclatasvir. This marks the beginning of interferon and ribavirin-free HCV treatment regime thus improving results dramatically and avoiding side effects. Currently, the regime includes 400 mg of sofosbuvir + 60 mg of the new drug which is selected depending on the genotype. This is taken once a day usually in the morning after breakfast. In the case of combination with telaprevir, the dosage varies depending on the RNA quantitative results and liver decompensation rates.

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Ledipasvir, telaprevir and daclatasvir are the first-ever approved HCV NS5A replication complex inhibitors, which implies that they dismantle and destroy the protein used by virus to replicate. Sofosbuvir + HCV NS5A replication complex inhibitors will prove to be life-saver for many Indian patients. This combo is proven to be with minimal side effects with US and EU results indicating nearly 90% SVR (sustained virological response) rates.

Sofosbuvir and its combination with ledipasvir, and another investigational drug velpatasvir have been licensed to the following companies to be produced generically:

• Aurobindo Pharma
• Biocon
• Cadila Healthcare
• Cipla
• Dr. Reddy’s Lab
• Hetero Labs
• Laurus Labs
• Mylan Laboratories
• Natco Pharma
• Ranbaxy Laboratories
• Sequent Scientific
• Strides Arco Labs
• Torrent Pharma

Table of Sofosbuvir + HCV NS5A Replication Complex Inhibitors

Sofosbuvir + HCV NS5A Replication Complex Inhibitors	Genotype Indicated
Sofosbuvir + Ledipasvir	1 & 4
Sofosbuvir + Telaprevir	1
Sofosbuvir + Daclatasvir	Pangenotype 1-4

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These combinations have worked significantly even in patients with other co-infections like HBV and HIV.

Sofosbuvir + HCV NS5A replication complex inhibitor is generally recommended for a minimum period of 3 months in patients without chronic liver disease and 6 months in patients with chronic liver disease. An RNA quantitative test is done after 1 month, 3 months and 6 months of treatment to detect the presence of the virus and the viral load in the blood.

The total cost of treatment for 6 months is approximately 1.2 lakhs with the drugs costing anywhere between 15,000 and 17,000 per month. Talk to your physician or gastroenterologist about starting your HCV treatment with a combination that works best for your genotype. You may need to do a genotyping first followed by other lab tests and imaging like liver function test, prothrombin or clotting time, complete blood counts and ultrasound of the abdomen. In some cases of suspected chronic liver disease, your doctor may ask to do an endoscopy.

The arrival of sofosbuvir and HCV NS5A replication complex inhibitor have given a new ray of hope for a HCV-free life with improvement of life quality for many patients in India and across the globe.