What is the recommended antiviral regimen for an adult with chronic hepatitis C infection and decompensated cirrhosis (Child‑Pugh B or C)?

Treatment for Hepatitis C with Decompensated Liver Disease

The treatment of choice for adults with chronic hepatitis C and decompensated cirrhosis (Child-Pugh B or C) is sofosbuvir/velpatasvir for 12 weeks with weight-based ribavirin (1,000 mg if <75 kg or 1,200 mg if ≥75 kg). 1

Critical Contraindications

Protease inhibitor-containing regimens are absolutely contraindicated in patients with decompensated (Child-Pugh B or C) cirrhosis due to substantially higher drug exposure and risk of severe toxicity. 1 This includes regimens containing voxilaprevir, glecaprevir/pibrentasvir, simeprevir, or paritaprevir. 2

Recommended Treatment Regimens

First-Line Therapy

• Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks is the preferred regimen for all genotypes in decompensated cirrhosis 1
• Ribavirin dosing: 1,000 mg daily if <75 kg; 1,200 mg daily if ≥75 kg 1
• Ribavirin can be initiated at 600 mg daily and titrated based on tolerance 1

Alternative for Ribavirin Intolerance

• Sofosbuvir/velpatasvir without ribavirin for 24 weeks can be used in patients with contraindications to ribavirin or poor tolerance 1
• Other NS5A inhibitor combinations (sofosbuvir/ledipasvir or sofosbuvir/daclatasvir) are also acceptable alternatives for 24 weeks without ribavirin 1

Genotype-Specific Considerations

Genotype 3 (Most Challenging)

• Requires 24 weeks of sofosbuvir/velpatasvir (or sofosbuvir/daclatasvir) plus ribavirin due to lower response rates 1
• In the ASTRAL-4 study, genotype 3 patients achieved only 50% SVR with 12 weeks without ribavirin, but 85% SVR with 12 weeks plus ribavirin 1

Genotypes 1,2,4,5,6

• 12 weeks of sofosbuvir/velpatasvir plus ribavirin is sufficient 1
• ASTRAL-4 demonstrated SVR rates of 88-100% for most genotypes with this regimen 1

Clinical Management Requirements

Treatment Setting

Patients with decompensated cirrhosis must be treated in experienced centers with easy access to liver transplantation. 1 Close monitoring during therapy is mandatory, with readiness to stop treatment if worsening decompensation occurs. 1

Pre-Treatment Testing

• Test all patients for hepatitis B (HBsAg and anti-HBc) before initiating therapy due to risk of HBV reactivation 2
• Assess Child-Pugh score and MELD score at baseline 1

Monitoring During Treatment

• Frequent clinical and laboratory assessment is necessary throughout treatment 1
• Monitor for signs of hepatic decompensation including worsening ascites, encephalopathy, or variceal bleeding 1
• Watch for HBV reactivation in coinfected patients 2

Expected Outcomes

Virologic Response

• Overall SVR12 rates in decompensated cirrhosis exceed 80-95% with appropriate regimens 1, 3
• Response rates are lower than in compensated cirrhosis but still highly effective 3

Clinical Improvement

• Approximately 50-60% of patients show improvement in MELD score and Child-Pugh class after achieving SVR 1, 4
• In one real-world study, 61.8% of Child-Pugh B patients improved to Child-Pugh A after treatment 4
• Patients with baseline MELD <15 have 51% chance of improved MELD score; those with MELD ≥15 have 81% chance of improvement 1

Transplant Considerations

Pre-Transplant Treatment Strategy

• Patients with MELD score <18-20 can be treated prior to transplantation 1
• Treatment should be initiated early to complete full course before potential transplantation 1
• Patients with MELD ≥18-20 should generally be transplanted first without antiviral treatment, unless waiting time exceeds 6 months 1

Delisting Potential

• Approximately 18-31% of treated patients may be delisted from transplant waiting lists due to clinical improvement 1, 3
• Patients with lower baseline MELD scores have higher chances of delisting 1
• No patients with baseline MELD >20 were delisted in reported studies 1

Common Pitfalls and Caveats

Risk Factors for Poor Outcomes

• Serum albumin <3.5 g/dL, MELD >14, or genotype 3 infection increase risk of further decompensation during therapy 3
• Previous decompensation at 1 month of treatment predicts persistent decompensation at follow-up 4

Ribavirin Management

• Hematological complications are common due to portal hypertension and splenomegaly 5
• Growth factors (erythropoietin or G-CSF) may be needed to manage cytopenias 5
• Starting ribavirin at lower dose (600 mg) with gradual titration improves tolerance 1

Post-SVR Surveillance

• Despite achieving SVR, patients with cirrhosis remain at risk for hepatocellular carcinoma and require continued surveillance with ultrasound every 6 months 5
• Ongoing monitoring for cirrhosis-related complications is necessary even after viral clearance 5