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

First-Line Treatment for Confirmed Hepatitis C Infection

For treatment-naïve patients with confirmed chronic HCV infection, use a pangenotypic direct-acting antiviral (DAA) regimen: either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status. 1, 2, 3

Recommended First-Line Regimens

Pangenotypic Options (All Genotypes)

• Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks is the preferred first-line option for all HCV genotypes (1-6) in both treatment-naïve and treatment-experienced patients, achieving SVR rates of 98% 1, 2, 3
• Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) is an equally effective alternative 1, 2, 3

These modern DAA regimens achieve sustained virologic response (SVR) rates exceeding 95% in most patient populations 1

Genotype-Specific Considerations (When Pangenotypic Regimens Unavailable)

Genotype 1a:

• Ledipasvir/sofosbuvir 90mg/400mg once daily for 12 weeks 4, 3
• Paritaprevir/ritonavir/ombitasvir plus dasabuvir with weight-based ribavirin for 12 weeks 4
• Sofosbuvir plus simeprevir for 12 weeks (if Q80K variant negative) 3

Genotype 1b:

• Ledipasvir/sofosbuvir for 12 weeks 3
• Paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks 3

Genotypes 2,4,5, and 6:

• Sofosbuvir/velpatasvir for 12 weeks without ribavirin 3

Genotype 3:

• Sofosbuvir/velpatasvir for 12 weeks (treatment-naïve without cirrhosis) 3
• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks (treatment-experienced or with cirrhosis) 3
• Sofosbuvir plus daclatasvir for 12 weeks is an alternative 1

Special Population Modifications

Patients with Compensated Cirrhosis

• Use the same pangenotypic regimens as non-cirrhotic patients 1, 2
• Extend glecaprevir/pibrentasvir duration to 12 weeks (from 8 weeks) 1, 2, 3
• Continue HCC surveillance with ultrasound every 6 months indefinitely, even after achieving SVR 1, 2, 3

Patients with Decompensated Cirrhosis

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1, 3
• Treatment should only be attempted in experienced centers until further safety data accumulates, particularly in patients with Child-Pugh scores >12 or MELD scores >20 4
• Interferon-containing regimens are absolutely contraindicated 4

HIV-Coinfected Patients

• Use the same HCV treatment regimens as HIV-negative patients 1, 2, 3
• Critical caveat: Carefully evaluate drug-drug interactions with antiretroviral therapy 1, 2, 3
• Daclatasvir dose adjustments required: 30mg with ritonavir/cobicistat-boosted regimens; 90mg with efavirenz 1

Pre-Treatment Assessment Requirements

Essential Testing Before Initiating Therapy

• HCV genotype and subtype determination (genotype 1a vs 1b affects treatment selection) 4
• Hepatitis B screening: Measure HBsAg and anti-HBc to detect current or prior HBV infection 5
• Fibrosis staging using noninvasive methods (transient elastography, serum biomarkers) or liver biopsy to determine treatment urgency and duration 4

Testing NOT Recommended

• IL28B genotyping has no role with modern DAA regimens 4
• HCV resistance testing should not be routinely performed prior to first-line therapy due to high SVR rates (>95%) regardless of baseline resistance variants 4

Critical Drug Interactions and Contraindications

Absolute Contraindications

• Do NOT use with P-gp inducers or moderate-to-strong CYP inducers (rifampin, St. John's wort, carbamazepine) as they significantly decrease DAA concentrations and reduce efficacy 5

Serious Drug Interaction - Amiodarone

• Coadministration with amiodarone is NOT recommended due to risk of serious symptomatic bradycardia, including fatal cardiac arrest 5
• If no alternative exists: require 48-hour inpatient cardiac monitoring, then daily heart rate monitoring for 2 weeks 5
• Patients on beta-blockers or with cardiac comorbidities are at increased risk 5

HBV Reactivation Risk

• Test all patients for HBsAg and anti-HBc before starting treatment 5
• Monitor HBV-coinfected patients for hepatitis flare during and after HCV treatment 5
• Some cases have resulted in fulminant hepatitis, hepatic failure, and death 5

Monitoring During and After Treatment

Virologic Monitoring

• Measure HCV RNA at: baseline, weeks 4 and 12 during treatment, end of treatment, and 12 weeks post-treatment 1
• SVR12 (undetectable HCV RNA 12 weeks after treatment completion) defines cure 1

Long-Term Surveillance

• Patients with cirrhosis require lifelong HCC surveillance with ultrasound every 6 months, even after achieving SVR 1, 2, 3
• Untreated patients and treatment failures should be reassessed with noninvasive fibrosis staging every 1-2 years 4

Common Pitfalls to Avoid

• Do not defer treatment in patients with advanced fibrosis (F3-F4) - these patients have the most urgent need and greatest short-term benefit from viral eradication 4
• Do not use genotype 1a-specific regimens without confirming subtype - genotype 1 that cannot be subtyped should be treated as 1a 4
• Do not forget to screen for HBV before starting DAAs - reactivation can be fatal 5
• Always verify drug-drug interactions before prescribing, particularly with antiretrovirals, cardiac medications, and acid-suppressing agents 1, 3
• Do not use older interferon-based regimens - they have been superseded by superior DAA-only regimens with higher efficacy and better tolerability 4