What is the recommended antiviral regimen for a patient with hepatitis C, genotype 1a (HCV genotype 1a) and compensated cirrhosis?

From the Guidelines

For patients with hepatitis C virus genotype 1a and compensated cirrhosis, the recommended antiviral regimen is sofosbuvir/ledipasvir for 12 weeks with daily weight-based ribavirin. This recommendation is based on the EASL guidelines 1 which suggest that treatment-experienced, DAA-naïve patients infected with genotype 1a with or without compensated cirrhosis should be treated with the fixed-dose combination of sofosbuvir and ledipasvir for 12 weeks with daily weight-based ribavirin.

Some key points to consider when treating these patients include:

• The presence of NS5A resistance-associated substitutions (RASs) at baseline, which may impact the choice of treatment regimen 1
• The importance of baseline laboratory testing, including complete blood count, liver function tests, renal function assessment, and HCV viral load quantification
• The need for monitoring for side effects during treatment, although these medications are generally well-tolerated
• The high cure rates exceeding 95% associated with these regimens, which target specific proteins essential for HCV replication, including NS3/4A protease, NS5A, and NS5B polymerase.

It's worth noting that other treatment options, such as glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, may also be effective for patients with genotype 1a and compensated cirrhosis, as suggested by the 2017 KASL clinical practice guidelines 1. However, the most recent and highest quality evidence supports the use of sofosbuvir/ledipasvir with ribavirin for 12 weeks in this patient population.

From the FDA Drug Label

MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1,2,3,4,5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of: Adult patients with genotype 1,2,3 or 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen.

The recommended antiviral regimen for a patient with hepatitis C, genotype 1a and compensated cirrhosis may include:

• Glecaprevir (MAVYRET), as it is indicated for the treatment of adult patients with HCV genotype 1 infection with compensated cirrhosis 2
• Sofosbuvir (SOVALDI), as it is indicated for the treatment of adult patients with genotype 1 chronic HCV infection with compensated cirrhosis as a component of a combination antiviral treatment regimen 3 Key points:
• The patient has compensated cirrhosis, which is a condition where the liver is damaged but still functioning.
• The patient has HCV genotype 1a, which is a specific strain of the hepatitis C virus.
• The recommended regimen may involve a combination of antiviral medications.

From the Research

Antiviral Regimen for Hepatitis C, Genotype 1a with Compensated Cirrhosis

• The recommended antiviral regimen for a patient with hepatitis C, genotype 1a (HCV genotype 1a) and compensated cirrhosis is glecaprevir plus pibrentasvir for 12 weeks, as shown in a study published in The Lancet. Infectious diseases 4.
• Another option is sofosbuvir/velpatasvir for 12 weeks, which has been shown to be highly effective and safe for treating patients with HCV genotypes 1-6 and compensated cirrhosis or advanced fibrosis, as reported in Liver international : official journal of the International Association for the Study of the Liver 5.
• Ledipasvir and sofosbuvir is also an effective treatment option for patients with genotype 1 HCV and compensated cirrhosis, with a sustained virological response rate of 96%, as demonstrated in a study published in Hepatology (Baltimore, Md.) 6.
• Real-world evidence from a large cohort of 5552 patients also supports the use of sofosbuvir/velpatasvir as a simple and effective treatment for HCV, with high sustained virological response rates in diverse patient populations, including those with compensated cirrhosis 7.
• A phase 3 trial conducted in Asia also demonstrated the efficacy and safety of sofosbuvir-velpatasvir for treatment of chronic HCV infection in patients with genotypes 1-6, including those with compensated cirrhosis 8.

Key Findings

• Glecaprevir plus pibrentasvir for 12 weeks achieved a sustained virological response rate of 99% in patients with HCV genotype 1a and compensated cirrhosis 4.
• Sofosbuvir/velpatasvir for 12 weeks achieved a sustained virological response rate of 98% in patients with HCV genotypes 1-6 and compensated cirrhosis or advanced fibrosis 5.
• Ledipasvir and sofosbuvir achieved a sustained virological response rate of 96% in patients with genotype 1 HCV and compensated cirrhosis 6.
• Sofosbuvir/velpatasvir achieved a sustained virological response rate of 98.9% in a large cohort of 5552 patients, including those with compensated cirrhosis 7.
• Sofosbuvir-velpatasvir achieved a sustained virological response rate of 97% in Asian patients with chronic HCV infection, including those with compensated cirrhosis 8.