What is the recommended treatment regimen for a patient with chronic hepatitis C?

Management of Chronic Hepatitis C

First-Line Treatment Recommendations

For most patients with chronic hepatitis C, sofosbuvir/velpatasvir for 12 weeks is the preferred pangenotypic regimen regardless of genotype, treatment history, or presence of compensated cirrhosis 1, 2, 3.

Alternative first-line options include:

• Glecaprevir/pibrentasvir: 8 weeks for non-cirrhotic patients, 12 weeks for compensated cirrhosis 1, 2, 3
• Ledipasvir/sofosbuvir: 12 weeks for genotypes 1,4,5, or 6 (can shorten to 8 weeks in treatment-naïve, non-cirrhotic patients with baseline HCV RNA <6 million IU/mL) 1, 2, 4

Genotype-Specific Considerations

Genotype 1

• All pangenotypic regimens achieve 95-98% SVR rates 1
• Ledipasvir/sofosbuvir for 12 weeks is highly effective (99% SVR in treatment-naïve patients) 4, 5
• For treatment-experienced patients with compensated cirrhosis, extend ledipasvir/sofosbuvir to 24 weeks 4

Genotype 2

• Sofosbuvir plus ribavirin for 12 weeks in non-cirrhotic patients 3, 6
• Extend to 16 weeks for cirrhotic patients 3

Genotype 3

• Sofosbuvir/velpatasvir for 12 weeks is recommended 1
• For treatment-experienced or cirrhotic patients, add ribavirin or extend to 24 weeks 1
• Alternative: Daclatasvir plus sofosbuvir for 12 weeks (non-cirrhotic) or 24 weeks with ribavirin (cirrhotic) 7, 3

Genotype 4

• Ledipasvir/sofosbuvir for 12 weeks 7, 1, 4
• Elbasvir/grazoprevir for 12 weeks 7
• Glecaprevir/pibrentasvir: 8 weeks (non-cirrhotic) or 12 weeks (cirrhotic) 7
• Ombitasvir/paritaprevir/ritonavir plus ribavirin for 12 weeks 7

Treatment Duration Based on Cirrhosis Status

Non-Cirrhotic Patients

• Glecaprevir/pibrentasvir: 8 weeks 7, 1, 2
• Ledipasvir/sofosbuvir: 8-12 weeks (8 weeks only if treatment-naïve with HCV RNA <6 million IU/mL) 1, 4
• Sofosbuvir/velpatasvir: 12 weeks 1

Compensated Cirrhosis (Child-Pugh A)

• Most regimens require 12 weeks 7, 1, 2
• Glecaprevir/pibrentasvir: 12 weeks 7, 1
• Treatment-experienced patients with cirrhosis on ledipasvir/sofosbuvir: extend to 24 weeks or add ribavirin for 12 weeks 4

Decompensated Cirrhosis (Child-Pugh B or C)

• Ledipasvir/sofosbuvir plus ribavirin for 12 weeks 1, 4
• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1
• Avoid glecaprevir/pibrentasvir in decompensated cirrhosis 1
• In patients with decompensated cirrhosis, start ribavirin at 600 mg daily and titrate up based on tolerance 4

Special Populations

Liver Transplant Recipients

• Ledipasvir/sofosbuvir plus ribavirin for 12 weeks for genotypes 1 or 4 without cirrhosis or with compensated cirrhosis 4
• High SVR rates (96-98%) achieved in transplant recipients without cirrhosis or with compensated cirrhosis 8

HIV/HCV Coinfection

• Use the same regimens and durations as HCV monoinfection 1, 2
• Sofosbuvir/velpatasvir achieves 92-95% SVR rates 1
• Check for drug-drug interactions with antiretroviral therapy 4

Treatment-Experienced Patients

• For genotype 1 with compensated cirrhosis: ledipasvir/sofosbuvir for 24 weeks or add ribavirin for 12 weeks 4
• For genotype 4: ombitasvir/paritaprevir/ritonavir plus ribavirin for 12 weeks 7
• Glecaprevir/pibrentasvir: 16 weeks for non-cirrhotic, 12 weeks for cirrhotic 7

Pre-Treatment Assessment

Critical pre-treatment testing includes:

• HBV screening (HBsAg and anti-HBc) is mandatory before initiating any DAA therapy 6, 4
• HCV genotype and viral load determination 3
• Assessment for cirrhosis using FIB-4 score, transient elastography, or other non-invasive methods 3
• Comprehensive medication reconciliation to identify drug-drug interactions 3

Important Drug Interactions

• P-glycoprotein inducers (rifampin, St. John's wort) significantly reduce sofosbuvir and ledipasvir levels 4
• Proton pump inhibitors can reduce ledipasvir absorption; separate dosing or use H2 antagonists 4
• Amiodarone with sofosbuvir-containing regimens can cause serious bradycardia 6

Monitoring During and After Treatment

• No routine laboratory monitoring is required during treatment for most patients 3
• HCV RNA at 12 weeks post-treatment to confirm SVR12 (undetectable HCV RNA = virological cure) 1, 2, 3
• Hepatic function panel to assess for normalization of liver enzymes after treatment 3
• For HBV/HCV coinfected patients, monitor for HBV reactivation during and after HCV treatment 6, 4

Critical Warnings and Pitfalls

HBV Reactivation

• HBV reactivation has resulted in fulminant hepatitis, hepatic failure, and death in HCV/HBV coinfected patients treated with DAAs 6, 4
• Initiate HBV antiviral therapy as clinically indicated before or during HCV treatment 6, 4

Ribavirin Considerations

• Weight-based dosing: 1000 mg (<75 kg) or 1200 mg (≥75 kg) daily in divided doses 7, 4
• In decompensated cirrhosis, start at 600 mg daily and titrate up 4
• Requires dose reduction in renal impairment (CrCl ≤50 mL/min) 6

Treatment Selection Caveats

• For genotype 1a, check for Q80K substitution if considering simeprevir-based regimens (58% SVR with Q80K present vs 84% without) 7
• Baseline NS5A resistance-associated substitutions do not significantly impair SVR with sofosbuvir/velpatasvir 9
• In treatment-naïve patients without cirrhosis considering 8-week ledipasvir/sofosbuvir, use caution in F3 fibrosis (higher relapse rates: 11/215 vs 3/216 for 12 weeks) 7