What is the treatment plan for a patient with a high Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) result?

Treatment Plan for High HCV PCR

All patients with confirmed chronic HCV infection and high viral load should receive immediate treatment with pangenotypic direct-acting antiviral (DAA) regimens, as modern therapy achieves cure rates exceeding 95-97% regardless of baseline viral load. 1, 2, 3

Immediate Pre-Treatment Assessment Required

Before initiating therapy, obtain the following essential tests:

• HCV genotype determination to select optimal regimen duration 3
• Liver fibrosis staging using non-invasive methods (FibroScan, APRI, FIB-4) or imaging to identify cirrhosis 3
• HIV testing to assess for co-infection and potential drug-drug interactions 3
• Hepatitis B surface antigen (HBsAg) and anti-HBc to screen for HBV co-infection, as HBV reactivation can occur during HCV treatment 4
• Complete blood count, comprehensive metabolic panel including liver enzymes and renal function 1

Note that elevated liver enzymes indicate active inflammation but are not a barrier to treatment initiation—normal transaminases are not required to start therapy. 3

First-Line Treatment Regimens

For Patients WITHOUT Cirrhosis (F0-F3):

Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks (cure rate 98%) 1, 3

• Single tablet, taken with or without food 4
• Pangenotypic—effective for all HCV genotypes 1

Alternative: Glecaprevir/pibrentasvir 300mg/120mg once daily for 8 weeks 1, 3

• Three tablets taken with food 1
• Also pangenotypic 1

For Patients WITH Compensated Cirrhosis (Child-Pugh A):

Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks 1

• Same regimen as non-cirrhotic patients 1

Alternative: Glecaprevir/pibrentasvir for 12 weeks (extended from 8 weeks) 1

For Patients WITH Decompensated Cirrhosis (Child-Pugh B or C):

Sofosbuvir/velpatasvir + weight-based ribavirin for 12 weeks 1

• Ribavirin: 1000mg daily if <75kg, 1200mg daily if ≥75kg 1
• Avoid protease inhibitor-containing regimens (simeprevir, paritaprevir, grazoprevir) as they are contraindicated in decompensated cirrhosis 1

Treatment Prioritization

Patients requiring immediate treatment without delay include: 1, 3

• Advanced fibrosis (F3) or any degree of cirrhosis (F4)—highest risk for hepatic decompensation and hepatocellular carcinoma 3
• Decompensated cirrhosis 1
• Clinically significant extrahepatic manifestations (cryoglobulinemia, HCV-related nephropathy) 1
• Active injection drug users or men who have sex with men with high-risk practices (transmission risk) 1
• Women of childbearing age wishing to conceive 2
• Hemodialysis patients 2

Treatment Monitoring

On-Treatment Monitoring:

Minimal monitoring is required with modern DAAs: 1

• Week 2: HCV RNA to assess adherence 1
• Week 4: HCV RNA (optional, mainly for adherence assessment) 1
• End of treatment (Week 8-12): HCV RNA 1
• Monitor for drug-drug interactions with all concurrent medications, including over-the-counter drugs 1
• Check CBC if using ribavirin to monitor for anemia 1

Post-Treatment Assessment:

HCV RNA at 12 weeks post-treatment (SVR12) to confirm cure 1, 2, 3

• SVR12 represents permanent viral eradication in >99% of cases 2
• Optional: HCV RNA at 24 weeks post-treatment (SVR24) for recently acquired hepatitis C, as late relapses have been reported 1

Critical Safety Considerations

Absolute Contraindications:

• Amiodarone co-administration with sofosbuvir-containing regimens (risk of severe bradycardia, cardiac arrest) 4
  • If no alternative exists, requires 48-hour inpatient cardiac monitoring 4

Drug-Drug Interactions to Avoid:

Do not co-administer with: 1

• P-glycoprotein inducers (rifampin, St. John's wort)
• Moderate-to-strong CYP inducers (carbamazepine, phenytoin, phenobarbital)
• Proton pump inhibitors with certain regimens
• These reduce DAA concentrations and lead to treatment failure 1

Ribavirin Dose Adjustments (if used):

• Reduce by 200mg decrements if hemoglobin drops below 10 g/dL 1
• Stop ribavirin if hemoglobin falls below 8.5 g/dL 1

Post-SVR Surveillance

For Patients With Advanced Fibrosis (F3) or Cirrhosis (F4):

Lifelong hepatocellular carcinoma (HCC) surveillance is mandatory: 2, 3

• Abdominal ultrasound every 6 months indefinitely 2, 3
• Risk of HCC is reduced but not eliminated after achieving cure 2

For Patients Without Advanced Fibrosis (F0-F2):

• No ongoing HCC surveillance required after SVR 2
• Liver disease typically resolves completely 2

Special Populations

Renal Impairment:

• No dose adjustment needed for sofosbuvir/velpatasvir in any degree of renal impairment, including dialysis 4
• Adjust ribavirin dose per prescribing information if CrCl ≤50 mL/min 4

HIV Co-infection:

• Use same DAA regimens as HIV-negative patients 1
• Check for drug-drug interactions with antiretroviral therapy and adjust accordingly 1

Clinical Benefits of Achieving Cure

Successful treatment provides: 2, 3

• Prevention of cirrhosis progression, hepatic decompensation, and liver-related death
• Reduced (but not eliminated) risk of hepatocellular carcinoma in cirrhotic patients
• Regression of liver fibrosis in patients with established fibrosis
• Improved quality of life and removal of stigma