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 modern approach to HCV treatment has shifted dramatically from selective treatment to universal access. Treatment is recommended for all patients with chronic HCV infection, except those with limited life expectancy due to non-liver-related comorbidities. 2, 1 This represents a fundamental change from older guidelines that restricted treatment based on fibrosis stage. 2

The rationale for universal treatment includes:

• Prevention of disease progression and complications 1
• Improvement in quality of life 1
• Prevention of HCV transmission to others 1
• Cure rates exceeding 95% with modern direct-acting antivirals (DAAs) 3

Priority Populations Requiring Immediate Treatment

While all patients should be treated, certain groups require urgent prioritization due to higher risk of complications or transmission:

Advanced Liver Disease

• Patients with significant fibrosis (METAVIR F3) or any stage of cirrhosis (F4) should be prioritized for immediate treatment. 2, 1 This includes both compensated (Child-Pugh A) and decompensated cirrhosis (Child-Pugh B and C). 2
• Patients with decompensated cirrhosis should be urgently treated with interferon-free regimens. 2 These patients face the highest mortality risk without treatment. 2
• One important caveat: patients with decompensated cirrhosis and MELD score ≥18-20 who are liver transplant candidates should generally be transplanted first and treated after transplantation. 1

Clinically Significant Extrahepatic Manifestations

• Symptomatic cryoglobulinemia vasculitis requires immediate treatment. 2, 1 This can present with purpura, weakness, arthralgias, and potentially life-threatening complications including rapidly progressive glomerulonephritis, CNS involvement, or intestinal ischemia. 2
• HCV immune complex-related nephropathy should be treated urgently. 2, 1
• Non-Hodgkin B-cell lymphoma associated with HCV warrants priority treatment. 2, 1
• Debilitating fatigue, even without advanced fibrosis, is an indication for prioritized treatment. 2, 1

High-Risk Comorbidities

• HIV or HBV coinfection requires priority treatment due to accelerated disease progression. 2, 1 Notably, all patients must be tested for HBV (HBsAg and anti-HBc) before initiating HCV treatment due to risk of HBV reactivation. 4
• Patients in the pre- or post-liver transplant setting should be prioritized. 2, 1
• Non-liver solid organ or stem cell transplant recipients require priority treatment. 1
• Patients with diabetes face accelerated fibrosis progression and should be prioritized. 1

Transmission Risk Groups

Individuals at risk of transmitting HCV should be prioritized regardless of fibrosis stage: 2, 1

• Active injection drug users 2, 1
• Men who have sex with men with high-risk sexual practices 2, 1
• Women of childbearing age who wish to get pregnant 2, 1
• Hemodialysis patients 2, 1
• Incarcerated individuals 2, 1

Treatment by Fibrosis Stage

Moderate Fibrosis (F2)

Treatment is justified and recommended for patients with moderate fibrosis (METAVIR F2). 2 This represents a clear indication without debate. 2

Minimal or No Fibrosis (F0-F1)

Patients with minimal or no fibrosis (F0-F1) without extrahepatic manifestations are still eligible for treatment, though timing may be individualized. 2, 1 However, given the high cure rates, excellent safety profile of modern DAAs, and prevention of transmission, treatment should generally not be deferred. 1 The decision to defer should consider patient preference, risk of progression, comorbidities, and age. 2

Absolute Contraindications

The only absolute contraindication to HCV treatment is limited life expectancy due to non-liver-related comorbidities. 2, 1 This is a critical distinction—liver-related life expectancy issues are actually indications for treatment, not contraindications.

Additional contraindications specific to certain regimens:

• Decompensated cirrhosis is a contraindication to regimens containing NS3-4A protease inhibitors. 1
• Certain drug interactions, particularly with CYP/P-gp-inducing agents, contraindicate specific DAA regimens. 1

FDA-Approved Indications

Modern DAA regimens like glecaprevir/pibrentasvir (MAVYRET) are approved for:

• Adult and pediatric patients ≥3 years with chronic HCV genotypes 1-6 4
• Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) 4
• Treatment-naive and treatment-experienced patients (including those who failed NS5A inhibitors or NS3/4A protease inhibitors, but not both) 4

Common Pitfalls to Avoid

1. Do not defer treatment in patients with advanced fibrosis or cirrhosis waiting for "better" therapies—current regimens achieve >95% cure rates and delay increases risk of complications. 2, 1

2. Do not exclude active substance users from treatment—they are a priority population for both individual benefit and public health transmission prevention. 2, 1

3. Do not forget HBV testing before initiating HCV treatment—HBV reactivation can cause fulminant hepatitis and death. 4

4. Do not use interferon-containing regimens in decompensated cirrhosis—these patients require interferon-free DAA regimens only. 2

5. Do not assume normal ALT excludes treatment indication—older guidelines restricted treatment to elevated ALT, but current guidelines recommend universal treatment regardless of ALT levels. 2