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.
‘Treatment for hepatitis C, if initiated early, is highly effective.’
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 :- 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
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