Treatment of Hepatitis C
Direct-acting antiviral (DAA) regimens are the standard of care for hepatitis C treatment, with cure rates exceeding 97% in most patient populations. 1
Recommended Treatment Regimens
First-line options:
- Sofosbuvir/velpatasvir for 8 weeks is recommended for patients with recently acquired hepatitis C 2
- Glecaprevir/pibrentasvir for 8 weeks is an alternative first-line option for recently acquired hepatitis C 2
- For chronic hepatitis C, treatment should be selected based on genotype, prior treatment history, and presence of cirrhosis 2, 3
Genotype-specific recommendations:
- Genotype 1 or 4: Sofosbuvir plus peginterferon alfa plus ribavirin for 12 weeks in treatment-naïve patients without cirrhosis or with compensated cirrhosis 4
- Genotype 2: Sofosbuvir plus ribavirin for 12 weeks in treatment-naïve and treatment-experienced patients without cirrhosis or with compensated cirrhosis 4
- Genotype 3: Sofosbuvir plus ribavirin for 24 weeks in treatment-naïve and treatment-experienced patients without cirrhosis or with compensated cirrhosis 4
Pre-Treatment Assessment
- HCV RNA quantitative assay and genotyping/subgenotyping should be performed prior to initiating antiviral treatment 2, 3
- Assessment of liver disease severity is essential before starting treatment to guide therapy decisions and predict prognosis 2
- Testing for HBV coinfection (HBsAg and anti-HBc) is required before starting HCV treatment due to risk of HBV reactivation 4
- Evaluation for potential drug-drug interactions with all concurrent medications is necessary 2
Treatment Monitoring
- HCV RNA or HCV core antigen detection should be performed at 12 weeks post-treatment (SVR12) to assess treatment success 2
- For most patients on DAA regimens with expected high SVR rates, checking SVR is optional except in patients at risk of reinfection 2
- Monitoring for adverse effects is important, though newer DAA regimens have significantly fewer side effects than older interferon-based therapies 2, 5
- Patients with cirrhosis require more intensive monitoring during treatment 3, 1
Special Populations
Patients with cirrhosis:
- Treatment should be initiated as soon as possible in patients with advanced fibrosis (F3-F4) 2
- Patients with decompensated cirrhosis require specialized care and may need adjusted treatment regimens 3
- After achieving SVR, patients with cirrhosis still require ongoing surveillance for hepatocellular carcinoma 1
Patients with renal impairment:
- Dosage recommendations cannot be made for patients with severe renal impairment or end-stage renal disease on standard sofosbuvir-based regimens 4
- Alternative regimens may be needed for patients with advanced kidney disease 6
HIV coinfection:
- Treatment follows the same principles as HCV monoinfection but requires careful attention to potential drug interactions with antiretroviral therapy 4, 7
Post-Treatment Follow-up
- Patients who achieve SVR have a greater than 99% chance of being cured of HCV infection 1
- Patients without advanced fibrosis who achieve SVR generally have excellent outcomes with resolution of liver disease 1
- Patients with cirrhosis who achieve SVR require continued surveillance for hepatocellular carcinoma every 6 months 3, 1
- The risk of hepatocellular carcinoma and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who achieve SVR 1
Common Pitfalls and Caveats
- Failure to screen for HBV coinfection before starting HCV treatment can lead to HBV reactivation 4
- Drug-drug interactions are common with DAA regimens and require careful medication review 2, 6
- Resistance-associated substitutions may develop in patients who fail DAA therapy, particularly with NS5A inhibitors, which can persist for years 8
- Sofosbuvir plus ribavirin alone is less effective than other DAA combinations and should be avoided when alternatives are available 5
- Renal function should be monitored during treatment as acute kidney injury has been reported in some patients on DAA therapy 5