What is the recommended treatment and follow-up plan for hepatitis C (HCV) infection?

Hepatitis C Treatment and Follow-Up

First-Line Treatment

All patients with confirmed chronic hepatitis C should be treated with pangenotypic direct-acting antiviral (DAA) regimens that achieve cure rates exceeding 95-97%, with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks being the preferred option across all genotypes. 1, 2, 3

Recommended Pangenotypic Regimens

• Sofosbuvir/velpatasvir 400mg/100mg: Single tablet once daily for 12 weeks (98% SVR rate across all genotypes) 1, 2, 3
• Glecaprevir/pibrentasvir: Three tablets (300mg/120mg total) once daily with food for 8 weeks in patients without cirrhosis or 12 weeks with compensated cirrhosis 1, 2, 3
• Sofosbuvir/velpatasvir/voxilaprevir: Single tablet once daily with food for 12 weeks (alternative option) 1

The 2020 EASL guidelines represent a significant evolution from the 2015 recommendations, moving away from genotype-specific regimens to simplified pangenotypic approaches that eliminate the need for genotype testing in most cases 1.

Pre-Treatment Assessment

Before initiating DAA therapy, obtain the following mandatory tests 2, 3:

• HCV RNA quantitative testing (baseline viral load)
• HCV genotype determination (though less critical with pangenotypic regimens)
• Fibrosis staging using noninvasive methods (FIB-4, APRI, or transient elastography/VCTE-LSM) 1, 3
• HBsAg and anti-HBc testing to screen for hepatitis B coinfection 4
• Comprehensive drug-drug interaction screening (particularly with antiretrovirals, cardiac medications, acid-suppressing agents) 2, 3

Treatment Modifications by Clinical Scenario

Compensated Cirrhosis (Child-Pugh A)

• Use the same pangenotypic regimens as non-cirrhotic patients 1, 2
• Extend glecaprevir/pibrentasvir duration to 12 weeks 1, 2, 3
• Sofosbuvir/velpatasvir remains 12 weeks 2, 3

Decompensated Cirrhosis

• Sofosbuvir/ledipasvir with ribavirin for 12-24 weeks showed 87-89% SVR rates in patients with Child-Pugh B and C cirrhosis 1
• Treatment can improve liver function and survival in this population 1

Liver Transplant Recipients

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks (applies pre- and post-transplant) 2

HIV/HCV Coinfection

• Use identical regimens as HCV monoinfected patients with equivalent virological outcomes 1, 2
• Perform dose adjustments or alterations only for drug-drug interactions with antiretrovirals 1, 2

Treatment Prioritization

Immediate treatment priority for 2, 3:

• Advanced fibrosis (≥F3) or any cirrhosis
• Pre- and post-liver transplant patients
• Severe extrahepatic manifestations
• Hepatocellular carcinoma
• Individuals at high risk of transmission (people who inject drugs, men who have sex with men with high-risk practices, women of childbearing age, hemodialysis patients) 5

Critical Drug-Drug Interactions

Absolute contraindications include P-glycoprotein (P-gp) inducers and moderate-to-strong CYP inducers, which significantly decrease DAA concentrations and reduce efficacy. 2, 4

• Do not use: Rifampin, St. John's wort, carbamazepine, phenytoin 4
• Amiodarone warning: Coadministration with sofosbuvir-containing regimens can cause serious symptomatic bradycardia, cardiac arrest, and may require pacemaker intervention 4
  • If amiodarone cannot be avoided, require 48-hour inpatient cardiac monitoring followed by daily outpatient heart rate monitoring for at least 2 weeks 4

Monitoring Protocol

During Treatment

• HCV RNA levels: Baseline, weeks 4 and 12 during treatment, end of treatment, and 12 weeks post-treatment 2, 3
• Liver function tests: Monitor ALT, AST, GGT (expect decreases during treatment) 6
• Platelet count: Expect increases during treatment 6

Definition of Cure

• SVR12: Undetectable HCV RNA 12 weeks after treatment completion using a sensitive molecular assay 2, 5
• SVR12 represents permanent viral eradication in >99% of cases 2, 5

Post-SVR Follow-Up

Patients Without Advanced Fibrosis (F0-F2)

• No ongoing HCC surveillance required after achieving SVR 1
• Can be discharged from specialized hepatology care 1

Patients With Advanced Fibrosis or Cirrhosis (F3-F4)

Lifelong HCC surveillance is mandatory even after achieving SVR, as these patients remain at reduced but ongoing risk for hepatocellular carcinoma. 1, 3, 5

• HCC surveillance: Ultrasound every 6 months indefinitely 3, 5
• Fibrosis reassessment: Early post-SVR decreases in VCTE-LSM and FIB-4 reflect decreased necroinflammation rather than true fibrosis regression 1
• Long-term post-SVR decreases indicate actual fibrosis regression 1

Monitoring for Reinfection

• At-risk patients (active injection drug use, high-risk sexual practices) require periodic HCV RNA testing 1
• Reinfection can be retreated with the same DAA regimens with similar efficacy 1

Retreatment Strategies for DAA Failure

The small percentage (3-5%) of patients who fail initial DAA therapy require specific retreatment approaches 2, 7:

Failed Sofosbuvir Alone or Sofosbuvir + Ribavirin

• Retreat with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir with ribavirin 1, 2
• Duration: 12 weeks for F0-F2, 24 weeks for F3-F4 1, 2

Failed NS5A Inhibitor-Containing Regimen

• Use sofosbuvir with a protease inhibitor (simeprevir) plus ribavirin 1, 2
• Duration: 12 weeks for genotype 1b or 4 without cirrhosis, 24 weeks for genotype 1a or cirrhosis 2

Failed Sofosbuvir/Simeprevir

• Retreat with sofosbuvir/daclatasvir or sofosbuvir/ledipasvir for 12-24 weeks with ribavirin 1

Common Pitfalls to Avoid

• Do not defer treatment in patients with advanced fibrosis (F3-F4), as they have the most urgent need and greatest short-term benefit from viral eradication 3
• Do not discontinue HCC surveillance in cirrhotic patients after achieving SVR—the risk persists lifelong 3, 5
• Always verify drug-drug interactions before prescribing, particularly with cardiac medications and antiretrovirals 2, 3
• Test for hepatitis B coinfection before starting treatment, as HBV reactivation can cause fulminant hepatitis, hepatic failure, and death during or after HCV treatment 4
• Monitor HBV-coinfected patients for clinical and laboratory signs of hepatitis flare during and after HCV treatment 4

Expected Clinical Benefits

Achieving SVR provides 2, 5:

• Prevention of cirrhosis complications
• Prevention of hepatocellular carcinoma (though risk persists in those with established cirrhosis)
• Prevention of hepatic decompensation and death
• Improvement in liver histology
• Resolution of extrahepatic manifestations
• Improved quality of life and removal of stigma