What is the recommended treatment for Hepatitis C (HCV)?

Treatment of Hepatitis C

First-Line Pangenotypic Regimens

For chronic hepatitis C infection, use either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks (depending on cirrhosis status), as these pangenotypic direct-acting antiviral regimens achieve cure rates exceeding 95% across all genotypes with excellent safety profiles. 1, 2

Treatment-Naïve Patients Without Cirrhosis

• Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks 3, 4
• Glecaprevir/pibrentasvir 300mg/120mg (three tablets) once daily for 8 weeks 3, 5
• Both regimens are taken with food and require no genotype testing 3, 1

Treatment-Naïve Patients With Compensated Cirrhosis (Child-Pugh A)

• Sofosbuvir/velpatasvir once daily for 12 weeks 3, 4
• Glecaprevir/pibrentasvir once daily for 8 weeks 3, 5

Treatment-Experienced Patients Without Cirrhosis

• Sofosbuvir/velpatasvir once daily for 12 weeks 3
• Glecaprevir/pibrentasvir once daily for 8 weeks 3, 5
• "Treatment-experienced" refers to prior pegylated interferon/ribavirin, sofosbuvir/ribavirin, or pegylated interferon/ribavirin/sofosbuvir regimens 3

Treatment-Experienced Patients With Compensated Cirrhosis

• Sofosbuvir/velpatasvir once daily for 12 weeks 3
• Glecaprevir/pibrentasvir once daily for 12 weeks (note the extended duration compared to non-cirrhotic patients) 3, 5

Pre-Treatment Assessment Requirements

Before initiating therapy, only three assessments are essential:

• Confirm HCV viremia by detecting HCV RNA or HCV core antigen 3
• Screen for hepatitis B by measuring HBsAg and anti-HBc, as HBV reactivation can cause fulminant hepatitis and death in coinfected patients 5, 4
• Assess for cirrhosis using non-invasive markers (FIB-4 or APRI scores) to determine treatment duration 3
• Check drug-drug interactions carefully, particularly with antiretrovirals, proton pump inhibitors, and other medications 3, 2

Genotype testing is not required when using pangenotypic regimens, though it remains useful in settings where available to optimize outcomes, particularly for genotype 3a patients with cirrhosis 3

Special Populations

Decompensated Cirrhosis (Child-Pugh B or C)

• Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 2, 4
• Ribavirin dosing: 1,000 mg daily (if <75 kg) or 1,200 mg daily (if ≥75 kg), divided twice daily with food 4

HIV-HCV Coinfection

• Use the same HCV regimens as HIV-negative patients 1, 2
• Adjust antiretroviral doses if drug-drug interactions exist 1
• No difference in efficacy compared to HCV monoinfection 3

Prior DAA Treatment Failure

For patients who failed NS5A inhibitor-based regimens (ledipasvir, velpatasvir, ombitasvir, elbasvir, daclatasvir):

• Genotype 1a: Sofosbuvir + ritonavir-boosted paritaprevir + ombitasvir + dasabuvir with ribavirin for 24 weeks 3
• Genotype 1b or 4 without cirrhosis: Same regimen for 12 weeks with ribavirin 3
• Alternative: Sofosbuvir + grazoprevir + elbasvir with ribavirin 3

For patients who failed NS3/4A protease inhibitor regimens without prior NS5A exposure:

• Glecaprevir/pibrentasvir for 12 weeks (no cirrhosis or compensated cirrhosis) 5

For patients who failed sofosbuvir-based regimens without NS5A or protease inhibitor exposure:

• Any first-line pangenotypic regimen can be used 3

Genotype-Specific Considerations When Genotyping Available

Genotype 3 With Compensated Cirrhosis

• Sofosbuvir/velpatasvir achieves lower SVR rates in this population compared to other genotypes 3
• Consider 12-week treatment with close monitoring, as efficacious retreatment exists if needed 3

Genotype 1a With Q80K Polymorphism

• Avoid sofosbuvir/simeprevir combination as this polymorphism reduces efficacy 2
• Use sofosbuvir/velpatasvir or glecaprevir/pibrentasvir instead 2

Post-Treatment Monitoring

Sustained Virologic Response Assessment

• Measure HCV RNA at 12 weeks post-treatment (SVR12) to confirm cure 2
• SVR testing can be omitted in adherent patients without high-risk behaviors, given the >95% cure rates with modern regimens 3
• Continue annual HCV RNA testing in patients with ongoing risk factors for reinfection (people who inject drugs, men who have sex with men) 3

Hepatocellular Carcinoma Surveillance

• For all patients with cirrhosis, continue ultrasound surveillance every 6 months indefinitely, even after achieving SVR 1, 2
• SVR reduces but does not eliminate HCC risk in cirrhotic patients 1

Critical Pitfalls to Avoid

Hepatitis B reactivation: Failure to screen for HBV before treatment can result in fulminant hepatitis and death; always measure HBsAg and anti-HBc 5, 4

Drug-drug interactions: Proton pump inhibitors can significantly reduce absorption of ledipasvir and velpatasvir; antiretrovirals may require dose adjustments 2

Underdosing cirrhotic patients: Treatment-experienced patients with compensated cirrhosis require 12 weeks of glecaprevir/pibrentasvir, not 8 weeks 5

Inadequate ribavirin dosing in decompensated cirrhosis: Weight-based dosing is essential; underdosing compromises efficacy 4

Premature discontinuation of HCC surveillance: Cirrhotic patients remain at risk for HCC after SVR and require lifelong surveillance 1, 2