Hepatitis C Treatment Guidelines

First-Line Treatment Recommendations

The American Association for the Study of Liver Diseases recommends initiating treatment with a pangenotypic direct-acting antiviral (DAA) regimen, such as sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks, for chronic hepatitis C infection 1, 2, 3
Pangenotypic regimens achieve sustained virologic response (SVR) rates exceeding 95-98% across all genotypes 1, 3

For treatment-naïve patients without cirrhosis, sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8 weeks are recommended, with SVR rates >95% 1, 2, 3
For treatment-naïve patients with compensated cirrhosis (Child-Pugh A), glecaprevir/pibrentasvir for 12 weeks is recommended 3

For genotype 1a (treatment-naïve, no cirrhosis), ledipasvir 90mg/sofosbuvir 400mg once daily for 12 weeks or paritaprevir/ritonavir/ombitasvir plus dasabuvir with ribavirin for 12 weeks are recommended 4, 5
For genotype 1a with cirrhosis, extend treatment to 24 weeks for ledipasvir/sofosbuvir 4
For genotype 1b, ledipasvir 90mg/sofosbuvir 400mg for 12 weeks or paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks are recommended 4, 5
For genotype 2, sofosbuvir/velpatasvir for 12 weeks without ribavirin or sofosbuvir plus weight-based ribavirin for 12 weeks (16 weeks if cirrhosis) are recommended 1, 4
For genotype 3, sofosbuvir/velpatasvir for 12 weeks (treatment-naïve without cirrhosis) or add ribavirin for 12 weeks if treatment-experienced or cirrhotic are recommended 1, 4

For HIV/HCV coinfected patients, use the same HCV treatment regimens as HCV mono-infected patients, with screening for drug-drug interactions with antiretroviral therapy 1, 2, 3
For liver transplant recipients, sofosbuvir/velpatasvir plus ribavirin for 12 weeks (pre- or post-transplant) or sofosbuvir/velpatasvir for 12 weeks without ribavirin for compensated cirrhosis (Child-Pugh A) are recommended 1, 3

Mandatory testing includes HCV RNA quantitative testing, HCV genotype and subtype determination, fibrosis staging, and comprehensive drug-drug interaction screening 3
Treatment prioritization is recommended for advanced fibrosis (≥F3) or any cirrhosis, pre- and post-liver transplant patients, severe extrahepatic manifestations, hepatocellular carcinoma, and active injection drug users 3, 4

HCV RNA levels should be monitored at baseline, weeks 4 and 12 during treatment, end of treatment, and 12 weeks post-treatment 3
SVR12 (undetectable HCV RNA 12 weeks after treatment completion) is the primary measure of cure, achieved in >99% of patients 3
For cirrhotic patients, continue hepatocellular carcinoma surveillance with ultrasound every 6 months even after achieving SVR 1, 2

Absolute contraindications include P-glycoprotein (P-gp) inducers and moderate-to-strong CYP3A4 inducers 3
Important interactions include ledipasvir/sofosbuvir with proton pump inhibitors and paritaprevir/ritonavir/ombitasvir plus dasabuvir with salmeterol and CYP3A4 substrates 5
Carefully evaluate all concomitant medications before initiating DAA therapy 1

Test for Q80K variant if using sofosbuvir plus simeprevir in cirrhotic patients, and use alternative regimen if Q80K positive 1, 5
Cirrhosis status determines treatment duration, with glecaprevir/pibrentasvir recommended for 8 weeks without cirrhosis and 12 weeks with compensated cirrhosis 4