What is the recommended treatment for a patient with active hepatitis C (HCV) infection?

Treatment of Active Hepatitis C Infection

All patients with active hepatitis C infection should be treated with pangenotypic direct-acting antiviral (DAA) regimens, with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks being the preferred first-line option across all genotypes, achieving cure rates exceeding 95-97%. 1, 2

Pre-Treatment Assessment

Before initiating antiviral therapy, several critical evaluations are mandatory:

• Test for hepatitis B coinfection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), as HBV reactivation can occur during HCV treatment and has resulted in fulminant hepatitis, hepatic failure, and death 3
• Obtain quantitative HCV RNA testing to establish baseline viremia, which may affect treatment duration with certain regimens 4
• Assess liver disease severity using noninvasive markers (such as transient elastography or serum biomarkers) to determine presence or absence of cirrhosis, as this influences treatment selection and duration 4
• Screen for HIV and hepatitis B coinfection, as these conditions accelerate liver fibrosis and require modified management 4
• Evaluate for drug-drug interactions with all concurrent medications, as DAAs have significant interaction potential 1

Important note: With pangenotypic regimens, HCV genotyping is no longer universally required for treatment-naive patients without cirrhosis, though it remains recommended for those with prior treatment failure 4

Recommended Treatment Regimens

First-Line Option: Sofosbuvir/Velpatasvir

For treatment-naive and treatment-experienced patients without cirrhosis or with compensated cirrhosis (Child-Pugh A):

• Sofosbuvir 400mg/velpatasvir 100mg as a single fixed-dose tablet once daily for 12 weeks 1, 2, 3
• This regimen achieves 98% SVR rates across all genotypes 1, 2
• Can be taken with or without food 3

For patients with decompensated cirrhosis (Child-Pugh B or C):

• Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 1, 2, 3
• Ribavirin dosing: 1,000 mg daily for patients <75 kg; 1,200 mg daily for patients ≥75 kg, divided twice daily with food 3

Alternative Option: Glecaprevir/Pibrentasvir

For treatment-naive patients without cirrhosis:

• Glecaprevir 300mg/pibrentasvir 120mg (three tablets) once daily with food for 8 weeks 1, 2, 5
• Achieves 97.6% SVR in intention-to-treat analysis 5

For patients with compensated cirrhosis:

• Same regimen extended to 12 weeks 1, 2

Critical caveat: Glecaprevir/pibrentasvir is contraindicated in patients with decompensated cirrhosis (Child-Pugh B or C) 6

Treatment Prioritization

Immediate treatment should be prioritized for:

• Patients with advanced fibrosis (≥F3) or any degree of cirrhosis 2, 7
• Pre- and post-liver transplant recipients 2
• Patients with severe extrahepatic manifestations 2
• Individuals at high risk of transmission (people who inject drugs, men who have sex with men with high-risk practices, women of childbearing age, hemodialysis patients) 2, 7
• Patients with hepatocellular carcinoma 2

Essential Counseling and Interventions

All patients require comprehensive education at diagnosis:

• Alcohol abstinence is mandatory, as there is no known safe level of alcohol use with chronic hepatitis C; excess alcohol accelerates fibrosis and increases hepatocellular carcinoma risk 4
• Patients with alcohol use disorder should be referred to addiction specialists, though ongoing alcohol use is not a contraindication to DAA therapy 4
• Education on preventing HCV transmission to others, emphasizing that exposure to infected blood is the primary transmission mode 4

Vaccination recommendations:

• Hepatitis A and B vaccination for all susceptible patients 4
• Pneumococcal vaccination for all patients with cirrhosis 4

Treatment Monitoring and Definition of Cure

• Monitor HCV RNA at baseline, during treatment (if clinically indicated), at end of treatment, and 12 weeks post-treatment 1
• Cure is defined as undetectable HCV RNA 12 weeks after treatment completion (SVR12), representing permanent viral eradication in >99% of cases 1, 7
• SVR12 prevents cirrhosis complications, hepatocellular carcinoma, hepatic decompensation, and death 2, 7

Post-SVR Follow-Up

Critical long-term management for patients with advanced disease:

• Patients with established cirrhosis (F4) or advanced fibrosis (F3) require lifelong hepatocellular carcinoma surveillance with ultrasound every 6 months indefinitely, even after achieving SVR, as they remain at reduced but ongoing risk 1, 2, 7
• Reassess fibrosis status post-SVR 2
• Monitor for reinfection in at-risk populations 2

Common Pitfalls and Special Considerations

Genotype-specific considerations:

• Genotype 3 is historically the most difficult to treat; avoid sofosbuvir/ledipasvir for genotype 3 as ledipasvir has considerably less potency against this genotype 4
• For genotype 3 with cirrhosis, consider extended duration or addition of ribavirin 4
• Genotype 3b patients may have suboptimal responses even with modern regimens 8

Patient-specific factors:

• Elderly patients (>75 years) may have higher rates of adverse effects requiring discontinuation 8
• Male patients and those with genotype 2 have higher dropout rates in real-world settings 8
• Baseline resistance-associated substitutions (RASs) may require treatment duration adjustment or ribavirin addition, particularly in treatment-experienced patients 1

Drug-drug interactions:

• Carefully review all concomitant medications, as DAAs are metabolized via CYP3A4 and transported by P-glycoprotein 9
• Avoid hepatotoxic drugs (acetaminophen >2g/day, certain herbal supplements) and nephrotoxic drugs (NSAIDs) in patients with cirrhosis 4

Retreatment after DAA failure:

• For patients who fail initial DAA therapy, retreatment options include sofosbuvir/velpatasvir, sofosbuvir/ledipasvir, or sofosbuvir/daclatasvir with ribavirin 2
• Genotyping is mandatory before retreatment as regimen selection and duration differ by genotype 4