Directly-acting Antivirals Appear Safe and Effective in Treating Hepatitis C

Highlights:

• Newer drugs called direct acting antivirals (DAA) have revolutionized the treatment of hepatitis C
• A systematic review showed that these drugs are safe as well as effective in the treatment of hepatitis C
• The addition of ribavirin improves the efficacy, but also increases the mild-to-moderate side effects

Researchers studied the role of the newer direct-acting antiviral (DAA) in the treatment of hepatitis C in terms of efficacy as well as safety. Their systematic review was published in the Annals of Internal Medicine.

Hepatitis C viral infection affects the liver, leading to the development of severe liver disease, including cirrhosis and liver cancer. It is transmitted through sexual contact, contact with blood products and from mother-to-child during childbirth. Among the 6 genotypes of the hepatitis C virus, infection with genotype 1 is the most common, followed by genotype 3. Earlier, treatment with interferon and ribavirin was not very effective and was found to be associated with side effects. The introduction of the directly-acting antiviral (DAAs) drugs like sofosbuvir, simprevir, daclatasvir, and ledipasvir has revolutionized the treatment of hepatitis C. DAAs directly act on the important steps of viral replication.

The researchers from Johns Hopkins University School of Medicine, Baltimore, University of Florida, Gainesville and University of North Carolina at Chapel Hill conducted a systematic review on studies evaluating the safety and efficacy of oral directly acting agents in the treatment of chronic HCV infection. They evaluated 42 studies on these drugs from databases MEDLINE and EMBASE since the time of their approval, up to 1^st November 2016. Each of these studies used at least 2 DAAs for a minimum duration of 8 weeks. The combinations that were studied are as follows:

For HCV 1 genotype:

• Grazoprevir-Elbasvir
• Paritaprevir-Ritonavir-Ombitasvir and Dasabuvir
• Sofosbuvir and either Simprevir, Daclatasvir, Ledipasvir or Velpatasvir

For HCV 2 genotype:

• Sofosbuvir and either Daclatasvir or Velpatasvir

For HCV 3 genotype:

• Sofosbuvir and either Daclatasvir, Ledipasvir or Velpatasvir

For HCV 4 genotype:

• Grazoprevir-Elbasvir
• Paritaprevir-Ritonavir-Ombitasvir
• Sofosbuvir and either Simprevir, Ledipasvir or Velpatasvir

For HCV genotypes 5 and 6:

• Sofosbuvir and either Ledipasvir or Velpatasvir

The researchers found that:

• The DAA combinations used for HCV genotype 1 infection showed high sustained virologic response (SVR) rates of more than 95% in patients without cirrhosis. These included patients with HIV infection. SVR refers to the absence of viral RNA in the blood at least 12 weeks after the completion of the treatment.
• Only 2 DAA regimens, Velpatasvir-Sofosbuvir and Daclatasvir-Sofosbuvir, are available for the treatment of HCV genotype 3 infection, though it is the second most common cause of HCV infection. Among these, the Velpatasvir-Sofosbuvir combination appears to be more effective in patients without cirrhosis.
• The SVR rates were slightly lower in patients with hepatic decompensation. According to current recommendations, these patients did not receive NS3 protease inhibitors like Simeprevir, Paritaprevir or Grazoprevir. They received treatment with Sofosbuvir and either Daclatasvir, Ledipasvir, or Velpatasvir. Side effects in this group of patients was higher than those in other groups.
• The addition of Ribavirin to certain DAA regimens improved the SVR rates, especially in patients with genotype 1a or 3 infection, cirrhosis, or prior treatment experience. However, ribavirin increased the incidence of mild-to-moderate adverse events like anemia, fatigue, and insomnia.
• Treatment with DAA regimens, especially with Velpatasvir-Sofosbuvir, for 12 weeks was effective in other genotypes like 2, 4, 5, or 6.
• The regimes are relatively safe with a relatively low incidence of serious adverse events and treatment discontinuation, even in patients with cirrhosis and HIV infection.

The researchers advise the readers to interpret the results of the study with caution due to some limitations in the study. There was a risk of bias in twenty three of the included studies. All except one study were funded by the industry. Patients with chronic hepatitis B infection were not included in the study. The risk of reactivation of hepatitis B, which has been noted following treatment of hepatitis C, was also not studied.

References :

1. Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS. Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review. Ann Intern Med. 21 March 2017

Source: Medindia