What is the recommended treatment for hepatitis C?

Recommended Treatment for Hepatitis C

All patients with chronic hepatitis C should be treated with pangenotypic direct-acting antiviral (DAA) regimens: either sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status. 1, 2

First-Line Treatment Regimens

Sofosbuvir/velpatasvir is the preferred pangenotypic regimen, achieving 98% SVR rates across all genotypes (1-6), administered as a single tablet once daily for 12 weeks. 1, 2 This regimen works regardless of prior treatment history or HIV coinfection status. 3, 2

Glecaprevir/pibrentasvir is an equally effective alternative, dosed as 3 tablets once daily with food:

• 8 weeks for patients without cirrhosis 1, 2
• 12 weeks for patients with compensated cirrhosis (Child-Pugh A) 1, 2

Treatment Selection by Clinical Scenario

Patients Without Cirrhosis or With Compensated Cirrhosis

• Sofosbuvir/velpatasvir for 12 weeks (all genotypes, treatment-naïve or experienced) 3, 1
• Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) 3, 1

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

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1, 4
• Ribavirin starting dose is 600mg daily, titrated up to 1000mg (<75kg) or 1200mg (≥75kg) in divided doses with food 4

Liver Transplant Recipients

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks (genotypes 1 or 4, pre- or post-transplant) 2, 4

HIV/HCV Coinfection

• Use the same regimens as HCV mono-infected patients with identical expected outcomes 2
• Check for drug-drug interactions with antiretroviral therapy 3, 4

Acute Hepatitis C

For recently acquired hepatitis C, treat with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for 8 weeks. 3 The 12-week duration showed 95% SVR versus 79% with 6 weeks, leading to early termination of shorter duration trials. 3

Pre-Treatment Assessment Requirements

Mandatory testing before initiating DAAs includes:

• HCV RNA quantitative testing with a sensitive assay (lower limit of detection <15 IU/mL) 3, 1
• HCV genotype and subtype determination 3, 1
• Hepatitis B testing (HBsAg and anti-HBc) to screen for HBV reactivation risk 4
• Fibrosis staging assessment 1, 2
• Comprehensive drug-drug interaction screening for all concurrent medications 3, 1

Treatment Monitoring Protocol

HCV RNA monitoring schedule:

• Baseline measurement 3, 2
• SVR12 (12 weeks post-treatment) is the primary measure of cure, achieved in >99% of patients who reach this endpoint 3, 2
• SVR24 (24 weeks post-treatment) should also be checked because late relapses have been reported 3

Given the high SVR rates (>95%) with modern pangenotypic regimens, checking SVR is dispensable except in patients with high-risk behaviors and those at risk of reinfection. 3

Critical Drug-Drug Interactions

Absolute contraindications include:

• P-glycoprotein (P-gp) inducers (rifampin, carbamazepine, phenytoin, St. John's wort) significantly decrease sofosbuvir concentrations and may lead to treatment failure 3, 2
• Moderate-to-strong CYP inducers reduce DAA efficacy 2

Check all medications including over-the-counter preparations and recreational drugs. 3 Consider temporarily stopping non-essential drugs like statins during the 8-12 week treatment period. 3

Treatment Prioritization

Immediate treatment priority for:

• Advanced fibrosis (≥F3) or any cirrhosis 3, 2
• Pre- and post-liver transplant patients 2
• Severe extrahepatic manifestations 2
• Hepatocellular carcinoma 2

Expected Outcomes and Long-Term Management

Modern DAA regimens achieve SVR rates exceeding 95% in most patient populations. 1, 2 Successful HCV eradication (achieving SVR) results in:

• Improvement in liver histology 1, 2
• Decreased risk of cirrhotic complications 1, 2
• Reduced occurrence of hepatocellular carcinoma 1, 2
• Improved survival rates 1, 2
• Resolution of extrahepatic manifestations 1, 2

Patients with advanced fibrosis (F3) or cirrhosis require lifelong HCC surveillance every 6 months even after achieving SVR, as they remain at risk for complications though at significantly reduced rates. 3, 1

Common Pitfalls and Caveats

Baseline resistance-associated substitutions (RASs) may affect treatment response and require adjustment of treatment duration or addition of ribavirin for certain regimens. 1 However, pangenotypic regimens like sofosbuvir/velpatasvir maintain high efficacy regardless of baseline resistance patterns. 3

HBV reactivation is a critical concern: Some cases have resulted in fulminant hepatitis, hepatic failure, and death in HCV/HBV coinfected patients receiving DAAs without HBV antiviral therapy. 4 Monitor for hepatitis flare during and after HCV treatment, and initiate HBV management as clinically indicated. 4

Patients with severe renal impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease: No dose recommendation exists for sofosbuvir due to higher exposures (up to 20-fold) of metabolites. 3 However, glecaprevir/pibrentasvir can be used safely in this population. 1

Treatment discontinuation rates are extremely low (<1%) due to the excellent tolerability of modern DAA regimens. 3 The most common adverse events are mild: fatigue, headache, nausea, and insomnia. 3 Regimens containing ribavirin have higher rates of mild-to-moderate adverse events, particularly anemia. 3