What is the recommended evaluation and treatment plan for a patient with chronic liver disease caused by hepatitis C virus?

Management of HCV-Associated Chronic Liver Disease

All patients with chronic hepatitis C and chronic liver disease should be offered direct-acting antiviral (DAA) therapy immediately, regardless of fibrosis stage, with treatment prioritized for those with significant fibrosis (F2-F4) or cirrhosis to prevent hepatic decompensation, hepatocellular carcinoma, and death. 1, 2

Initial Evaluation

Disease Severity Assessment

• Assess fibrosis stage using non-invasive methods first: Vibration-controlled transient elastography (liver stiffness measurement) is preferred over biopsy, with LSM <8 kPa indicating minimal fibrosis and LSM ≥10 kPa indicating advanced fibrosis/cirrhosis 2
• Calculate FIB-4 score as an alternative: <1.45 suggests minimal fibrosis, >3.25 indicates advanced fibrosis/cirrhosis 2
• Obtain baseline laboratory tests: ALT, AST, bilirubin, albumin, platelet count, INR, and creatinine 1, 2
• Measure HCV RNA quantitatively using a sensitive assay (lower limit of detection <15 IU/mL) 1
• Determine HCV genotype to guide treatment selection, though pangenotypic regimens have simplified this requirement 1, 3

Hepatitis B Screening (Critical)

• Test all patients for HBsAg and anti-HBc before initiating DAA therapy to identify HBV coinfection, as HBV reactivation during HCV treatment can cause fulminant hepatitis, hepatic failure, and death 4

Hepatitis A Vaccination Status

• Determine need for hepatitis A vaccination in all HCV-positive patients 1

Hepatocellular Carcinoma Surveillance

• Perform baseline abdominal ultrasound in all patients with cirrhosis, as HCC risk is 1-4% annually once cirrhosis develops 2, 5

Treatment Recommendations

First-Line Therapy for Non-Cirrhotic and Compensated Cirrhosis (Child-Pugh A)

Pangenotypic DAA regimens achieve >95% cure rates and should be initiated without delay: 1, 2, 3, 6

• Glecaprevir/pibrentasvir (Maviret): 8 weeks for treatment-naïve patients without cirrhosis or with compensated cirrhosis 3, 6
• Sofosbuvir/velpatasvir (Epclusa): 12 weeks for all genotypes, treatment-naïve or treatment-experienced, without cirrhosis or with compensated cirrhosis 3, 6
• Ledipasvir/sofosbuvir: 12 weeks for genotype 1,4,5, or 6 without cirrhosis or with compensated cirrhosis; 24 weeks for treatment-experienced patients with compensated cirrhosis 4

Decompensated Cirrhosis (Child-Pugh B or C)

Patients with decompensated cirrhosis require urgent interferon-free DAA therapy in experienced centers: 1, 7, 2

• Ledipasvir/sofosbuvir + ribavirin: 12 weeks for genotype 1 with decompensated cirrhosis 4
• Ribavirin dosing: Start at 600 mg daily in decompensated patients, titrate to weight-based dosing (1000 mg if <75 kg, 1200 mg if ≥75 kg) divided twice daily with food 4
• Patients with MELD ≥18-20 and transplant listing: Transplant first, then treat post-transplant if waiting time <6 months; treat before transplant if waiting time >6 months 1

Post-Liver Transplant Recipients

• Ledipasvir/sofosbuvir + ribavirin: 12 weeks for genotype 1 or 4 liver transplant recipients without cirrhosis or with compensated cirrhosis 4

Priority Populations Requiring Immediate Treatment (Regardless of Fibrosis Stage)

Treatment should not be delayed in: 1

• Patients with clinically significant extrahepatic manifestations (symptomatic cryoglobulinemic vasculitis, HCV immune complex nephropathy, non-Hodgkin B-cell lymphoma)
• HIV or HBV coinfection
• Active injection drug users (counsel on reinfection risk)
• Men who have sex with men with high-risk sexual practices (counsel on reinfection risk)
• Women of childbearing age planning pregnancy
• Hemodialysis patients
• Incarcerated individuals
• Patients with debilitating fatigue

Contraindications to Treatment

Absolute contraindications (historical interferon-based regimens, now largely obsolete): 1

• Pregnancy (for ribavirin-containing regimens)
• Uncontrolled severe psychiatric illness
• Decompensated cirrhosis (for interferon-based regimens only; DAAs are indicated)

Relative contraindications requiring specialist management: 1

• Active alcohol use or injection drug use (defer treatment until abstinent ≥6 months for interferon-based regimens; DAAs can be used with caution)
• Severe cytopenias
• Autoimmune disease
• Major depression

Treatment not recommended: 1

• Limited life expectancy from non-liver-related comorbidities

Monitoring During Treatment

• HCV RNA at week 4 (optional for adherence assessment) and at end of treatment 2
• Liver function tests and complete blood count every 4 weeks during treatment, more frequently if using ribavirin 2
• Monitor for drug-drug interactions using www.hep-druginteractions.org 1

Post-Treatment Follow-Up

Confirming Cure

• Measure HCV RNA at 12 weeks post-treatment (SVR12): Undetectable HCV RNA confirms cure in >99% of patients 7, 2, 6

Long-Term Management Based on Fibrosis Stage

Patients without cirrhosis (LSM <8 kPa or FIB-4 <1.45) and no cofactors:

• Discharge to primary care after confirming SVR12 2

Patients with advanced fibrosis (F3) or cirrhosis (F4):

• Continue specialized hepatology care indefinitely 2, 5
• HCC surveillance with abdominal ultrasound every 6 months for life, as HCC risk persists despite viral cure 7, 2, 5
• Laboratory monitoring (ALT, AST, bilirubin, albumin, platelets, INR) every 6-12 months 2
• Endoscopic variceal screening if cirrhosis with portal hypertension 2

Patients with persistent cofactors (alcohol use, metabolic dysfunction-associated steatotic liver disease, obesity):

• Require ongoing specialized follow-up to manage residual liver disease risk 2, 5

Critical Pitfalls to Avoid

• Do not defer treatment in patients with significant fibrosis (F2-F4): Disease progression, HCC development, and mortality risk mandate immediate treatment 1, 2
• Do not use interferon-based regimens in decompensated cirrhosis: Interferon is absolutely contraindicated and can precipitate hepatic failure 1, 7
• Do not discontinue HCC surveillance after SVR in cirrhotic patients: HCC risk persists at 0.5-1% annually despite viral cure 7, 2, 5
• Do not overlook HBV screening: Failure to test for HBV before DAA initiation risks fatal HBV reactivation 4
• Do not exclude active substance users from treatment: Modern DAAs are safe and effective in this population, and treatment reduces transmission risk 1