What is the treatment indication for a patient with a confirmed diagnosis of hepatitis C virus (HCV)?

Treatment Indication for Hepatitis C

All patients with confirmed chronic hepatitis C virus (HCV) infection should be considered for antiviral treatment, regardless of disease stage or fibrosis level, unless they have absolute contraindications or limited life expectancy from non-liver-related conditions. 1

Who Should Be Treated

Universal Treatment Eligibility

• Every adult and pediatric patient (≥3 years old) with chronic HCV infection and detectable HCV RNA is a treatment candidate 2, 1
• Treatment should not be delayed or deferred based on fibrosis stage alone, as early treatment prevents disease progression, reduces transmission risk, and improves quality of life 1, 3
• The goal is HCV eradication (sustained virologic response, or SVR) to prevent liver cirrhosis, hepatocellular carcinoma, and mortality 2

Priority Populations Requiring Immediate Treatment

Highest Priority (Treat Urgently):

• Patients with advanced fibrosis (METAVIR F3) or any stage of cirrhosis (F4), including compensated cirrhosis (Child-Pugh A) 2, 1
• Patients with decompensated cirrhosis (Child-Pugh B or C) using interferon-free regimens 2, 1, 4
• Patients with clinically significant extrahepatic manifestations, including symptomatic cryoglobulinemic vasculitis, HCV-related nephropathy, or B-cell non-Hodgkin lymphoma 2, 1
• Liver transplant recipients or candidates 1, 4

High Priority:

• Patients with moderate fibrosis (METAVIR F2) 2, 5
• HIV or HBV coinfected patients 2, 1
• Individuals at risk of transmitting HCV: active injection drug users, men who have sex with men with high-risk practices, women of childbearing age planning pregnancy, hemodialysis patients, incarcerated individuals 2, 1
• Patients with debilitating fatigue regardless of fibrosis stage 2, 1
• Patients with comorbidities accelerating disease progression: diabetes, obesity, other organ transplant recipients 1

Standard Priority:

• Patients with minimal or no fibrosis (F0-F1) without extrahepatic manifestations remain eligible for treatment, though timing may be individualized based on patient preference, age, and availability of newer therapies 2, 1

Absolute Contraindications to Treatment

General Contraindications

• Limited life expectancy from non-liver-related comorbid conditions that cannot be remediated by HCV treatment or transplantation 2, 1
• Current pregnancy (for ribavirin-containing regimens) 2
• Known hypersensitivity to the specific direct-acting antiviral agents being considered 2

Regimen-Specific Contraindications

• Decompensated cirrhosis is a contraindication to NS3-4A protease inhibitor-containing regimens 1
• Severe renal impairment (eGFR <30 mL/min/1.73 m²) requires caution with sofosbuvir-based regimens, though treatment is possible with close monitoring 2, 6
• Significant drug-drug interactions with CYP/P-glycoprotein-inducing agents may contraindicate certain DAA regimens 2, 1

Historical Contraindications (No Longer Applicable with Modern DAAs)

The following were contraindications to peginterferon/ribavirin therapy but are not contraindications to modern interferon-free direct-acting antiviral regimens:

• Uncontrolled psychiatric illness or autoimmune disease 2
• Solid organ transplantation (except liver) 2
• Advanced age 2

Required Pre-Treatment Assessment

Confirmatory Testing

• HCV RNA quantitative assay must be positive to confirm active infection (anti-HCV antibody alone is insufficient) 2
• HCV genotype and subtype determination (essential for regimen selection) 2

Disease Severity Evaluation

• Fibrosis staging using non-invasive methods (FIB-4 score, transient elastography, or serum biomarkers) 2, 1, 5
• For cirrhotic patients: Child-Pugh score calculation, assessment for portal hypertension, and ultrasound to exclude hepatocellular carcinoma 2, 1

Coinfection Screening

• All patients must be tested for hepatitis B (HBsAg and anti-HBc) before starting HCV treatment due to risk of HBV reactivation 4
• HIV testing in at-risk populations 2, 1

Drug Interaction Assessment

• Comprehensive medication reconciliation including over-the-counter drugs and supplements 2, 1
• Evaluation of potential drug-drug interactions using validated resources 2, 1

Treatment Goals and Outcomes

Primary Goal

• Sustained virologic response (SVR): undetectable HCV RNA at 12 weeks after treatment completion 2, 7
• SVR represents virologic cure in >99% of patients 2

Clinical Benefits of Achieving SVR

• Significant reduction in all-cause mortality across all fibrosis stages 3, 7
• Prevention or regression of hepatic fibrosis in >90% of patients 2
• Decreased incidence of hepatocellular carcinoma and hepatic decompensation 2, 3, 8
• Improvement in extrahepatic manifestations 3, 7
• Enhanced quality of life, cognitive function, and work productivity 7

Common Pitfalls to Avoid

• Do not defer treatment based solely on mild fibrosis, as long-term studies demonstrate mortality benefits even in non-cirrhotic patients who achieve SVR 3
• Do not overlook HBV screening, as HBV reactivation during HCV treatment can cause fulminant hepatitis and death 4
• Do not assume cirrhotic patients are cured of all risk after SVR—they require continued surveillance for hepatocellular carcinoma with ultrasound every 6 months and endoscopic screening for varices 5, 7
• Do not delay treatment in patients with decompensated cirrhosis with MELD <18-20, as they can benefit from pre-transplant treatment with interferon-free regimens 1