What is the recommended treatment for hepatitis C genotype 1a?

Treatment of Hepatitis C Genotype 1a

For treatment of hepatitis C genotype 1a, the recommended first-line therapy is either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks in patients without cirrhosis and for 8-12 weeks in those with compensated cirrhosis. 1

First-Line Treatment Options for HCV Genotype 1a

Treatment-Naïve Patients

Without Cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks 1
• Glecaprevir/pibrentasvir for 8 weeks 1, 2

With Compensated (Child-Pugh A) Cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks 1
• Glecaprevir/pibrentasvir for 8 weeks 1

Treatment-Experienced Patients

Without Cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks 1
• Glecaprevir/pibrentasvir for 8 weeks 1

With Compensated (Child-Pugh A) Cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks 1
• Glecaprevir/pibrentasvir for 12 weeks 1

Efficacy of Recommended Regimens

Both recommended regimens demonstrate excellent efficacy in clinical trials:

• Sofosbuvir/velpatasvir achieved 100% SVR12 (sustained virologic response at 12 weeks post-treatment) in previously treated HCV genotype 1a patients 1
• Glecaprevir/pibrentasvir achieved 99% SVR12 in HCV genotype 1a infected patients with compensated cirrhosis 1
• In an integrated analysis of treatment-naïve patients, 8 weeks of glecaprevir/pibrentasvir achieved an overall SVR12 rate of 97.6% across all genotypes 2

Special Considerations

Resistance-Associated Substitutions (RASs)

• For patients with NS5A RASs, treatment decisions may need to be modified 1
• When using elbasvir/grazoprevir (an alternative regimen), patients without NS5A RASs should receive 12 weeks of treatment, while those with NS5A RASs may require 16 weeks plus ribavirin 1

Prior DAA Treatment Failure

• For patients who failed previous NS5A inhibitor-containing regimens, sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is recommended 3
• For patients who failed sofosbuvir-based treatment without an NS5A inhibitor, 16 weeks of glecaprevir/pibrentasvir has shown >90% SVR12 rates 4

Alternative Regimens for HCV Genotype 1a

If the first-line options are not suitable, these alternatives may be considered:

• Ledipasvir/sofosbuvir for 12 weeks (can be shortened to 8 weeks in treatment-naïve patients without cirrhosis and with baseline HCV RNA <6,000 IU/mL) 1
• Elbasvir/grazoprevir for 12 weeks (without NS5A RASs) or 16 weeks with ribavirin (with NS5A RASs) 1
• Ombitasvir/paritaprevir/ritonavir plus dasabuvir and ribavirin for 12 weeks (without cirrhosis) or 24 weeks (with compensated cirrhosis) 1

Monitoring and Follow-up

• Assessment of SVR12 (HCV RNA testing 12 weeks after completion of treatment) is recommended to confirm cure 5
• For patients with cirrhosis, continued monitoring for hepatocellular carcinoma with ultrasound every 6 months is recommended, even after achieving SVR 6, 5

Common Pitfalls and Caveats

• Drug-drug interactions must be carefully evaluated before initiating direct-acting antiviral therapy 1, 5
• The Q80K polymorphism in NS3 can affect treatment response with certain regimens (particularly sofosbuvir plus simeprevir) 1
• Patients with decompensated cirrhosis require special consideration and may need ribavirin-containing regimens 5
• HIV co-infected patients can receive the same HCV treatment regimens, but dose adjustments may be needed due to interactions with antiretroviral drugs 6, 5

The treatment landscape for HCV has evolved significantly with these highly effective direct-acting antiviral regimens, offering cure rates exceeding 95% with short treatment durations and excellent safety profiles.