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

Treatment of Confirmed Hepatitis C Infection

Initiate treatment with a pangenotypic direct-acting antiviral (DAA) regimen: sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks is the preferred first-line therapy for this patient with confirmed HCV infection. 1, 2

Determining the Optimal Regimen

Since the HCV genotype is not specified in the lab results provided, a pangenotypic regimen is essential. The two primary options are:

• Sofosbuvir/velpatasvir (SOF/VEL): 400mg/100mg once daily for 12 weeks achieves SVR rates exceeding 95-98% across all genotypes 1, 2
• Glecaprevir/pibrentasvir: 8 weeks for non-cirrhotic patients or 12 weeks for compensated cirrhosis 1, 2

Sofosbuvir/velpatasvir is the preferred choice because it demonstrates consistent efficacy across all genotypes (1-6) with a simple 12-week duration regardless of cirrhosis status or treatment history 3. This regimen achieved 98% SVR in genotype 1 patients, 99% in genotype 2, and high rates across all other genotypes in the ASTRAL trials 3.

Pre-Treatment Requirements

Before initiating therapy, you must:

• Test for hepatitis B: Measure HBsAg and anti-HBc to identify current or prior HBV infection, as HBV reactivation can occur during HCV treatment and may result in fulminant hepatitis or death 4
• Determine HCV genotype: While pangenotypic regimens work across all genotypes, knowing the specific genotype helps optimize treatment duration and predict response 2
• Assess fibrosis stage: Determine presence or absence of cirrhosis through imaging, biopsy, or non-invasive markers 2
• Screen for drug-drug interactions: Review all concomitant medications, particularly antiretrovirals, proton pump inhibitors, and cardiac medications 2, 5

Treatment Duration and Ribavirin Considerations

For most patients:

• 12 weeks of SOF/VEL without ribavirin is sufficient for treatment-naïve and treatment-experienced patients, regardless of cirrhosis status 3, 1
• Ribavirin is NOT routinely needed with SOF/VEL for genotypes 1,2,4,5, or 6 3, 5

Special consideration for genotype 3: If the patient has genotype 3 with the NS5A Y93H resistance-associated substitution (RAS) or is treatment-experienced with cirrhosis, add weight-based ribavirin (1000mg if <75kg or 1200mg if ≥75kg daily) for 12 weeks 3. Alternatively, extend SOF/VEL to 24 weeks without ribavirin if ribavirin is contraindicated 3.

Genotype-Specific Alternatives (If Genotype Known)

For Genotype 1:

• SOF/VEL 12 weeks without ribavirin (preferred) 3
• Ledipasvir/sofosbuvir 12 weeks without ribavirin (alternative) 2
• Sofosbuvir + daclatasvir 12 weeks: treatment-naïve patients without ribavirin; treatment-experienced genotype 1a may benefit from ribavirin addition 3

For Genotype 2:

• SOF/VEL 12 weeks without ribavirin achieves 99% SVR 3, 5
• Sofosbuvir + daclatasvir 12 weeks without ribavirin (alternative) 3, 5
• Critical pitfall: Do NOT use ledipasvir/sofosbuvir for genotype 2, as ledipasvir lacks activity against this genotype 5

For Genotype 3:

• SOF/VEL 12 weeks without ribavirin for treatment-naïve patients without cirrhosis 3
• Add ribavirin or extend to 24 weeks for treatment-experienced patients or those with cirrhosis 3, 6
• Sofosbuvir + daclatasvir: 12 weeks without ribavirin for treatment-naïve non-cirrhotic patients; 24 weeks with ribavirin for cirrhotic patients 3
• Genotype 3 with cirrhosis remains the most difficult-to-treat population, with lower SVR rates (89-94%) compared to other genotypes 6, 7

Monitoring Protocol

• Baseline: HCV RNA quantitative, genotype, HBsAg, anti-HBc, CBC, CMP, fibrosis assessment 2, 4
• Week 4: HCV RNA (optional but helpful to assess early response) 2
• Week 12 (end of treatment): HCV RNA, CBC, CMP 2
• Week 24 (12 weeks post-treatment): HCV RNA to confirm SVR12—this is the primary measure of cure 2

For cirrhotic patients: Continue hepatocellular carcinoma surveillance with ultrasound every 6 months indefinitely, even after achieving SVR 1, 2

Critical Drug-Drug Interactions to Avoid

• Absolute contraindications: P-glycoprotein inducers (rifampin, St. John's wort) and moderate-to-strong CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital) significantly reduce DAA concentrations 2
• Proton pump inhibitors: Can reduce ledipasvir/sofosbuvir absorption; if using this regimen, omeprazole ≤20mg should be taken 4 hours before DAA 2
• HIV antiretrovirals: Daclatasvir requires dose adjustment to 30mg with ritonavir/cobicistat-boosted regimens or 90mg with efavirenz 3, 5

Common Pitfalls to Avoid

• Do not extend treatment to 16 or 24 weeks for genotype 2 patients receiving SOF/VEL, as 12 weeks is equally effective regardless of cirrhosis 5
• Do not use sofosbuvir + ribavirin alone for genotype 3, as this combination is suboptimal with lower SVR rates 3
• Do not use ledipasvir/sofosbuvir for genotype 3, as ledipasvir has considerably less potency against this genotype 3
• Do not forget HBV screening: Failure to test for HBV before treatment can result in life-threatening HBV reactivation 4

Expected Outcomes

With appropriate DAA therapy, expect:

• SVR12 rates >95% across all genotypes with pangenotypic regimens 1, 2
• Undetectable HCV RNA by week 4 in 75-90% of patients (rapid virologic response) 8
• Excellent tolerability: Most common adverse effects are mild fatigue and headache; serious adverse events are rare (<1%) 2, 8