What is the first-line treatment for reactive Hepatitis C (Hep C) management?

First-Line Treatment for Reactive Hepatitis C

The first-line treatment for reactive hepatitis C is a pangenotypic direct-acting antiviral (DAA) regimen consisting of either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks, depending on cirrhosis status and treatment history. 1

Treatment Recommendations Based on HCV Genotype

Genotype 1 Infection

• For patients with genotype 1 infection (both 1a and 1b), recommended first-line options include:
  • Sofosbuvir/velpatasvir for 12 weeks 2, 1
  • Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) 1
  • Sofosbuvir/ledipasvir for 12 weeks (8 weeks may be considered in treatment-naïve patients without cirrhosis if baseline HCV RNA is <6 million IU/ml) 2

Genotypes 2 and 3 Infection

• For genotype 2 infection:
  • Sofosbuvir/velpatasvir for 12 weeks 2, 1
  • Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) 1
• For genotype 3 infection:
  • Sofosbuvir/velpatasvir for 12 weeks 2, 1
  • Sofosbuvir/daclatasvir for 12 weeks 2

Genotypes 4,5, and 6 Infection

• For genotypes 4,5, and 6:
  • Sofosbuvir/velpatasvir for 12 weeks 2, 1
  • Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) 1

Special Considerations

Patients with Cirrhosis

• For patients with compensated cirrhosis (Child-Pugh A):
  • Same regimens as non-cirrhotic patients, but treatment duration may need to be extended to 12 weeks for glecaprevir/pibrentasvir 1, 3
• For patients with decompensated cirrhosis (Child-Pugh B or C):
  • Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2, 3
  • Ribavirin dosing: 1,000 mg/day for patients <75 kg and 1,200 mg/day for those ≥75 kg, divided twice daily 3

HIV Co-infection

• The same HCV treatment regimens can be used in HIV-coinfected patients as in patients without HIV infection, with dose adjustments needed in case of interactions with antiretroviral drugs 1
• The dose of daclatasvir must be adjusted to 30 mg in HIV-coinfected patients receiving ritonavir- or cobicistat-boosted atazanavir or cobicistat-boosted elvitegravir, and to 90 mg in HIV-coinfected patients receiving efavirenz 2

Monitoring During Treatment

• Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment 3
• Monitor HCV RNA levels at baseline, weeks 4 and 12 during treatment, at the end of treatment, and 12 weeks after completion to assess sustained virologic response (SVR) 2
• For patients with cirrhosis, continue monitoring for hepatocellular carcinoma with ultrasound every 6 months, even after achieving SVR 1

Treatment Efficacy

• Modern DAA regimens achieve SVR rates exceeding 95% in most patient populations 4, 5
• The combination of sofosbuvir/velpatasvir has shown SVR rates of 98% in genotype 1 infection and similarly high rates in other genotypes 2
• Treatment success is defined as achieving sustained virologic response (SVR), which means undetectable HCV RNA 12 weeks after treatment completion 1

Common Pitfalls and Caveats

• HBV reactivation can occur in HCV/HBV co-infected patients during or after DAA therapy; monitor for hepatitis flare and initiate appropriate HBV treatment if indicated 3
• Resistance-associated substitutions (RASs) may affect treatment outcomes, particularly for NS5A inhibitors in certain patient groups (genotype 1a or 3, cirrhosis, prior non-responders) 6
• Drug-drug interactions must be carefully evaluated before initiating DAA therapy, particularly in patients on multiple medications 2
• The older peginterferon-based regimens are no longer recommended as first-line therapy due to lower efficacy rates and significant side effects 4, 5