What is the recommended treatment for a patient with Hepatitis C Virus (HCV) infection?

Hepatitis C Treatment

All patients with chronic hepatitis C infection should be treated with pangenotypic direct-acting antiviral (DAA) regimens, with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks as the preferred first-line option across all genotypes, achieving 98% cure rates. 1, 2

Pre-Treatment Assessment Requirements

Before initiating DAA therapy, you must obtain:

• HCV RNA quantitative testing to confirm active infection 1, 2
• HCV genotype and subtype determination (though pangenotypic regimens eliminate genotype-specific treatment decisions) 1, 3
• Fibrosis staging using non-invasive methods (FibroScan, APRI, FIB-4) or liver biopsy if uncertainty exists 1, 2
• Hepatitis B testing (HBsAg and anti-HBc) - this is mandatory as HBV reactivation can cause fulminant hepatitis and death during DAA therapy 4, 5, 6
• Comprehensive drug-drug interaction screening - absolute contraindications include P-glycoprotein inducers and moderate-to-strong CYP inducers 1

First-Line Treatment Algorithm

For Patients Without Cirrhosis or With Compensated Cirrhosis (Child-Pugh A):

Option 1 (Preferred): Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks 1, 2, 4

• Single tablet formulation
• 98% SVR rates across all genotypes (1-6) 1, 2
• Can be taken with or without food 4

Option 2 (Alternative): Glecaprevir/pibrentasvir 1, 2

• 8 weeks for patients without cirrhosis 1, 2
• 12 weeks for patients with compensated cirrhosis 1, 2
• Must be taken with food 2

For Patients With Decompensated Cirrhosis (Child-Pugh B or C):

Sofosbuvir/velpatasvir PLUS ribavirin for 12 weeks 1, 4

• Ribavirin dosing: 1,000 mg daily if <75 kg; 1,200 mg daily if ≥75 kg, divided twice daily with food 4
• Start ribavirin at 600 mg daily and adjust based on tolerance 1
• Do NOT use protease inhibitor-containing regimens (glecaprevir/pibrentasvir) in decompensated cirrhosis 1
• SVR rates of 87-89% in Child-Pugh B and C patients 2

Treatment Prioritization - Who Needs Immediate Treatment

The following patients require immediate treatment initiation rather than deferral 1, 2:

• Advanced fibrosis (≥F3) or any degree of cirrhosis
• Pre- and post-liver transplant recipients
• Severe extrahepatic manifestations (symptomatic cryoglobulinemia, HCV immune complex nephropathy)
• Hepatocellular carcinoma
• Individuals at high risk of HCV transmission

Important caveat: Even patients with minimal or no fibrosis (F0-F2) should be scheduled for treatment rather than deferred, though timing may be more flexible 2

Special Populations

HIV/HCV Coinfection:

Use the same DAA regimens as HCV mono-infected patients with identical expected outcomes 1, 3

Critical drug-drug interactions to avoid: 7

• Sofosbuvir/ledipasvir should NOT be used with tenofovir/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or elvitegravir/cobicistat (or use with caution and frequent renal monitoring)
• Paritaprevir/ombitasvir/dasabuvir should NOT be used with efavirenz, etravirine, nevirapine, or elvitegravir/cobicistat

Liver Transplant Recipients:

Sofosbuvir/velpatasvir plus ribavirin for 12 weeks for both pre- and post-transplant settings 1

Patients on Anticonvulsants:

First-generation anticonvulsants (phenytoin, carbamazepine, phenobarbital) are potent CYP inducers and theoretically contraindicated 1. However, real-world data shows SVR can still be achieved despite this interaction 8. If coadministration cannot be avoided, proceed with treatment but monitor closely.

Monitoring Protocol

During Treatment: 1

• HCV RNA at baseline, weeks 4 and 12, and end of treatment
• Liver function tests
• For cirrhotic patients: close monitoring for side effects and decompensation

Post-Treatment: 1, 2

• HCV RNA at 12 weeks post-treatment (SVR12) - this defines cure
• SVR12 (undetectable HCV RNA 12 weeks after treatment completion) is achieved in >99% of patients who reach this endpoint and represents viral eradication 1, 2

Retreatment for DAA Failure

If patient failed sofosbuvir alone or sofosbuvir plus ribavirin: 1

• Retreat with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir with ribavirin
• Duration: 12 weeks for F0-F2; 24 weeks for F3-F4

If patient failed NS5A inhibitor-containing regimen: 1

• Use sofosbuvir with a protease inhibitor (grazoprevir/elbasvir or simeprevir) plus ribavirin
• Duration: 12 weeks for genotype 1b or 4 without cirrhosis; 24 weeks for genotype 1a or with cirrhosis

Post-SVR Surveillance

Lifelong HCC surveillance is mandatory for patients with advanced fibrosis or cirrhosis (F3-F4) even after achieving SVR 2

• Ultrasound every 6 months indefinitely 2
• Fibrosis reassessment 2
• Monitor for reinfection in at-risk patients (people who inject drugs, men who have sex with men) 2

Expected Clinical Benefits of Achieving SVR

Viral eradication provides: 1, 2

• 70-90% reduction in liver-related mortality
• 70-90% reduction in overall mortality
• 75-90% reduction in HCC incidence
• Prevention of hepatic decompensation
• Improvement in liver histology
• Resolution of extrahepatic manifestations
• Improved quality of life

Critical Safety Warning

Hepatitis B reactivation can occur during DAA therapy and has resulted in fulminant hepatitis, hepatic failure, and death 4, 5, 6. This occurs because DAAs rapidly suppress HCV, removing viral interference that was suppressing HBV replication. Monitor HCV/HBV coinfected patients for hepatitis flare during and after treatment, and initiate HBV antiviral therapy as clinically indicated 4, 5.