What are the indications for Hepatitis C Virus (HCV) treatment?

Indications for Hepatitis C Virus (HCV) Treatment

All patients with chronic HCV infection should be offered treatment without delay, regardless of disease stage or fibrosis level. 1

Universal Treatment Recommendation

The current paradigm has shifted from selective treatment to universal treatment for all patients with chronic HCV infection. 2, 1 This approach is based on the ability of modern direct-acting antivirals to prevent complications, improve quality of life, and prevent transmission. 1

Priority Groups Requiring Immediate Treatment

Highest Priority (Urgent Treatment Required)

• Decompensated cirrhosis (Child-Pugh B and C): These patients require urgent treatment with interferon-free regimens. 2, 1 However, patients with MELD scores ≥18-20 who are liver transplant candidates should generally be transplanted first and treated after transplantation. 1

• Advanced fibrosis or cirrhosis (METAVIR F3-F4): Treatment should be prioritized and not deferred in these patients due to high risk of progression to liver-related complications. 2, 3

High Priority (Treatment Should Be Prioritized)

Regardless of fibrosis stage, the following groups should receive priority treatment: 2

• Clinically significant extrahepatic manifestations: 2, 1

  • Symptomatic vasculitis associated with HCV-related mixed cryoglobulinemia 2
  • HCV immune complex-related nephropathy 2
  • Non-Hodgkin B-cell lymphoma 2

• Coinfections: 2, 1

  • HIV coinfection 2
  • HBV coinfection 2

• Transplant-related: 2, 1

  • Pre- or post-liver transplant setting 2
  • Non-liver solid organ or stem cell transplant recipients 1

• Transmission risk groups: 2, 1

  • Active injection drug users 2
  • Men who have sex with men with high-risk sexual practices 2
  • Women of childbearing age who wish to get pregnant 2
  • Hemodialysis patients 2
  • Incarcerated individuals 2

• Other high-risk conditions: 2, 1

  • Debilitating fatigue 2
  • Diabetes 1
  • Rapid disease progression risk due to comorbidities 1

Standard Priority

• Moderate fibrosis (METAVIR F2): Treatment is justified in these patients. 2

• Minimal or no fibrosis (METAVIR F0-F1): These patients are still eligible for treatment, though timing may be individualized based on patient preference, age, and comorbidities. 2, 1 The decision to defer should consider the risk of disease progression and availability of new therapies. 2

Absolute Contraindications to Treatment

Treatment is not recommended in the following circumstances: 2, 1

• Limited life expectancy due to non-liver-related comorbidities 2, 1
• Decompensated cirrhosis is a contraindication specifically to regimens containing NS3-4A protease inhibitors 1
• Significant drug interactions, particularly with CYP/P-gp-inducing agents 1

FDA-Approved Indications

Current FDA-approved direct-acting antivirals are indicated for: 4, 5

• All HCV genotypes (1-6) in adult and pediatric patients ≥3 years old 4
• Without cirrhosis or with compensated cirrhosis (Child-Pugh A) 4, 5
• Treatment-experienced patients who previously failed regimens containing NS5A inhibitors or NS3/4A protease inhibitors (but not both) 4

Pre-Treatment Assessment Requirements

Before initiating treatment, the following assessments are mandatory: 1, 4

• HBV testing: All patients must be tested for HBsAg and anti-HBc before starting HCV treatment due to risk of HBV reactivation. 1, 4
• Liver disease severity: Using non-invasive methods such as liver stiffness measurement and fibrosis biomarker panels 1, 3
• Portal hypertension assessment in cirrhotic patients 1
• Renal function, diabetes status, and obesity evaluation 1

Common Pitfalls to Avoid

• Do not defer treatment in patients with advanced fibrosis or cirrhosis waiting for "better" therapies—current regimens achieve >90% cure rates and prevent life-threatening complications. 6
• Do not overlook extrahepatic manifestations such as cryoglobulinemia, which are independent indications for treatment regardless of liver disease stage. 2
• Do not forget HBV screening—failure to test can result in fulminant hepatitis from HBV reactivation during or after HCV treatment. 4
• Do not assume cirrhotic patients are cured of HCC risk after achieving sustained virologic response—they require continued HCC surveillance. 2, 1