What is the recommended treatment for a patient diagnosed with Hepatitis C (Hep C)?

Treatment of Hepatitis C

All adults with chronic hepatitis C should receive direct-acting antiviral (DAA) therapy, as these regimens cure HCV infection in >95% of patients with minimal side effects and short treatment durations of 8-12 weeks. 1, 2

First-Line Treatment Regimens

The modern approach to HCV treatment has been revolutionized by pangenotypic DAA regimens that work across all genotypes with high efficacy 2, 3:

Recommended Options

• Sofosbuvir/velpatasvir (400mg/100mg): One tablet once daily for 12 weeks 2, 4

  • Achieves 98% SVR rates across genotypes 4
  • Can be taken with or without food 5

• Glecaprevir/pibrentasvir (300mg/120mg): Three tablets once daily with food 2, 4

  • 8 weeks for patients without cirrhosis 2, 6
  • 12 weeks for patients with compensated cirrhosis or treatment-experienced patients 2

Treatment Duration by Clinical Scenario

For treatment-naïve patients without cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks OR glecaprevir/pibrentasvir for 8 weeks 2

For treatment-naïve patients with compensated cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks OR glecaprevir/pibrentasvir for 8-12 weeks 2

For treatment-experienced patients with compensated cirrhosis:

• Sofosbuvir/velpatasvir for 12 weeks OR glecaprevir/pibrentasvir for 12-16 weeks (depending on genotype) 2

Special Populations Requiring Modified Regimens

Decompensated Cirrhosis (Child-Pugh B or C)

Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 2, 5:

• Ribavirin dosing: 1000mg daily if <75kg, 1200mg daily if ≥75kg, divided in two doses with food 5
• Starting dose may be 600mg in decompensated patients, titrated up as tolerated 5
• Critical caveat: Protease inhibitor-containing regimens (like glecaprevir/pibrentasvir) are contraindicated in decompensated cirrhosis 2

Severe Renal Impairment (eGFR <30 mL/min or hemodialysis)

Glecaprevir/pibrentasvir is the treatment of choice 2:

• Sofosbuvir-based regimens should be avoided due to accumulation of metabolites 2
• Standard dosing of glecaprevir/pibrentasvir can be used safely 2

HIV-HCV Coinfection

Use the same HCV treatment regimens as HIV-negative patients 2:

• Carefully evaluate drug-drug interactions with antiretroviral therapy 2, 4
• Refer to interaction databases before prescribing 2

Liver Transplant Recipients

Sofosbuvir/velpatasvir plus ribavirin for 12 weeks for genotype 1 or 4 patients without cirrhosis or with compensated cirrhosis 5

Pre-Treatment Assessment

Mandatory Testing

Before initiating any DAA therapy, test for:

• Hepatitis B screening: HBsAg and anti-HBc 1, 5, 7

  • HBV reactivation has caused fulminant hepatitis, hepatic failure, and death in coinfected patients 5, 7
  • Patients positive for HBsAg require HBV monitoring and may need concurrent HBV treatment 1

• HCV RNA quantitative assay 6, 4

• HCV genotype/subtype 6, 4

• Assessment of liver fibrosis stage (non-invasive methods preferred) 1, 6

• HIV testing with antigen/antibody assay 1

Drug Interaction Screening

Evaluate all concurrent medications for potential interactions before starting DAAs 2, 4:

• This is particularly critical for patients on antiretrovirals, immunosuppressants, or cardiovascular medications 2

Treatment Monitoring and Follow-Up

On-Treatment Monitoring

On-treatment viral load monitoring is no longer required due to high efficacy and low breakthrough rates of current DAAs 2:

• Monitor for adverse effects, though these are minimal with modern regimens 6, 3
• For patients on ribavirin, monitor hemoglobin for anemia 1

Post-Treatment Assessment

Check HCV RNA at 12 weeks post-treatment (SVR12) to confirm cure 2, 6:

• SVR12 represents cure in >99% of patients 6, 8
• SVR12 is highly concordant with SVR24 (>97% positive predictive value) 8
• For most patients with expected high SVR rates, checking SVR is optional except in those at risk of reinfection 6

Long-Term Surveillance After SVR

Patients with cirrhosis require indefinite HCC surveillance 1, 2:

• Ultrasound every 6 months, even after achieving SVR 2, 6
• Risk of HCC is significantly reduced but not eliminated 6, 9

Patients without cirrhosis generally have excellent outcomes with resolution of liver disease 6, 10:

• Routine surveillance not required in most cases 10
• Consider monitoring in patients with ongoing risk factors (obesity, diabetes, alcohol use) 10

Benefits of Treatment

Achieving SVR provides substantial clinical benefits 1, 9:

• Reduces all-cause mortality 1, 9
• Decreases risk of cirrhosis progression and hepatic decompensation 1, 9
• Reduces HCC incidence by 2.5- to 5-fold 9
• Improves or stabilizes hepatic fibrosis 1, 9
• Resolves extrahepatic manifestations (cryoglobulinemia, glomerulonephritis) 1
• Improves quality of life and productivity 1

Treatment Priorities

Prioritize treatment for the following groups 1:

• Advanced fibrosis (F3-F4) or any stage of cirrhosis 1, 6
• Pre- and post-liver transplant patients 1
• Severe extrahepatic manifestations (cryoglobulinemia, glomerulonephritis) 1
• Patients with HCC who have completed curative therapy 1

Common Pitfalls to Avoid

• Do not withhold treatment from patients with ongoing substance use: Treatment-committed individuals with substance use achieve comparable SVR rates to those without 1
• Do not use protease inhibitors in decompensated cirrhosis: This can lead to serious adverse events 2
• Do not use sofosbuvir in severe renal impairment: Metabolite accumulation poses safety concerns 2
• Do not forget HBV screening: Failure to screen and monitor can result in fatal HBV reactivation 5, 7
• Do not discontinue HCC surveillance after SVR in cirrhotic patients: Risk persists despite viral cure 2, 6