What is the recommended treatment for a patient with Hepatitis C (HCV) and compensated liver disease?

Treatment of Hepatitis C with Compensated Liver Disease

All patients with chronic Hepatitis C and compensated liver disease (Child-Pugh A cirrhosis or no cirrhosis) should be treated with direct-acting antiviral (DAA) therapy, with sofosbuvir/velpatasvir for 12 weeks being the preferred pangenotypic regimen regardless of genotype or prior treatment history. 1, 2

Who Must Be Treated

• All treatment-naïve and treatment-experienced patients with compensated chronic liver disease related to HCV must be considered for therapy if they are willing to be treated and have no contraindications 3

• Treatment should be initiated without delay in patients with significant fibrosis (METAVIR F2 or F3) or compensated cirrhosis (METAVIR F4) 3

• Patients with clinically significant extrahepatic manifestations (symptomatic vasculitis, HCV-related cryoglobulinemia, immune complex nephropathy) require urgent treatment 3

First-Line Treatment Regimens

Preferred Pangenotypic Options (All Genotypes)

Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks is the preferred first-line regimen for most patients with compensated liver disease, regardless of HCV genotype, treatment history, or presence of compensated cirrhosis 1, 2

Glecaprevir/pibrentasvir is an equally effective alternative:

• 8 weeks for patients without cirrhosis 1, 2, 4
• 12 weeks for patients with compensated cirrhosis 1, 2, 4

Genotype-Specific Alternatives

For Genotype 1:

• Ledipasvir/sofosbuvir 90mg/400mg once daily for 12 weeks (can be shortened to 8 weeks in treatment-naïve patients without cirrhosis if baseline HCV RNA <6 million IU/mL) 3, 2, 5
• Elbasvir/grazoprevir for 12 weeks (if no NS5A resistance-associated substitutions present) 5
• All these regimens achieve 95-98% SVR rates 2, 5

For Genotype 3:

• Sofosbuvir/velpatasvir for 12 weeks is recommended 1, 2
• Consider adding ribavirin or extending to 24 weeks for treatment-experienced patients or those with compensated cirrhosis 1, 2

For Genotype 4:

• Ledipasvir/sofosbuvir for 12 weeks 2
• Elbasvir/grazoprevir for 12 weeks 2
• Glecaprevir/pibrentasvir for 8 weeks (non-cirrhotic) or 12 weeks (compensated cirrhosis) 2

Treatment Duration Based on Cirrhosis Status

Without Cirrhosis:

• Glecaprevir/pibrentasvir: 8 weeks 1, 4
• Ledipasvir/sofosbuvir: 8-12 weeks (8 weeks only if treatment-naïve with HCV RNA <6 million IU/mL) 1, 5
• Sofosbuvir/velpatasvir: 12 weeks 1

With Compensated Cirrhosis (Child-Pugh A):

• Most regimens require 12 weeks of treatment 1, 2, 4
• IFN-free combination regimens should be strongly preferred over interferon-based therapy 3

Treatment-Experienced Patients

For patients previously treated with NS5A inhibitors:

• Glecaprevir/pibrentasvir for 16 weeks (without cirrhosis) or 16 weeks (with compensated cirrhosis) 4

For patients previously treated with NS3/4A protease inhibitors:

• Glecaprevir/pibrentasvir for 12 weeks regardless of cirrhosis status 4

For patients previously treated with peginterferon/ribavirin/sofosbuvir only:

• Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis) for genotypes 1,2,4,5,6 4
• For genotype 3: 16 weeks regardless of cirrhosis status 4

Pre-Treatment Assessment

Essential testing before initiating therapy:

• HCV genotype determination (critical for treatment selection) 1
• HCV RNA quantification using sensitive assay (lower limit <15 IU/mL) 3
• Assessment for cirrhosis using FIB-4 score, transient elastography, or other non-invasive methods 1
• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) to detect current or prior HBV infection 4
• Comprehensive medication reconciliation to identify drug-drug interactions 1

IL28B genotyping is NOT recommended as it has no role in treatment decisions with DAAs 3

Systematic HCV resistance testing prior to treatment is NOT recommended due to limited access to reliable testing and lack of consensus on interpretation 3

Contraindications and Precautions

No absolute contraindications exist for DAAs approved in the EU region 3

Critical warnings:

• Protease inhibitors (simeprevir, paritaprevir/ritonavir, grazoprevir) are contraindicated in Child-Pugh B or C decompensated cirrhosis but can be used safely in compensated cirrhosis 3
• Sofosbuvir should be used with caution in severe renal impairment (eGFR <30 mL/min/1.73 m²) 3
• Sofosbuvir is contraindicated with amiodarone if the patient cannot switch to alternative therapy 3
• Avoid P-glycoprotein inducers (rifampin, carbamazepine, phenytoin, St. John's wort) with sofosbuvir 3

Monitoring During and After Treatment

During treatment:

• HCV RNA at baseline, week 4, week 12, end of treatment 2
• Hepatic function panel to monitor liver enzymes 1

Post-treatment:

• HCV RNA at 12 weeks post-treatment (SVR12) is necessary to confirm virological cure (undetectable HCV RNA = sustained virologic response) 1, 2, 5
• Some guidelines recommend additional testing at 24 weeks post-treatment 2

Post-SVR Surveillance

Patients with cirrhosis must undergo lifelong HCC surveillance even after achieving SVR 3, 6

• The risk of HCC is substantially reduced but not eliminated after viral eradication 3
• Increased risk for HCC persists up to 10 years after HCV eradication in patients with cirrhosis or high FIB-4 score 3

Special Considerations

HIV/HCV coinfected patients:

• Use the same regimens and durations as HCV monoinfection 1, 2
• Sofosbuvir/velpatasvir achieves 92-95% SVR rates 1, 2
• Check for drug-drug interactions with antiretroviral therapy 3

Ribavirin dosing when required:

• Weight-based: 1000 mg daily (<75 kg) or 1200 mg daily (≥75 kg) 3
• Can be started at 600 mg daily and adjusted based on tolerance in decompensated patients 3
• Requires dose reduction in renal impairment (CrCl ≤50 mL/min) 1

Common Pitfalls to Avoid

• Do not use interferon-based regimens when DAA options are available—they are less effective and poorly tolerated in cirrhotic patients 3
• Do not delay treatment in patients with F2-F4 fibrosis—these patients benefit most from immediate therapy 3
• Do not discontinue HCC surveillance after SVR in cirrhotic patients—cancer risk persists 3
• Do not use protease inhibitors in decompensated cirrhosis (Child-Pugh B or C) 3