What are the next steps for an elderly male with a reactive Hepatitis C (HCV) antibody test?

Next Steps for Elderly Male with Reactive HCV Antibody

The immediate next step is to order HCV RNA testing to confirm current infection, as a reactive HCV antibody test alone cannot distinguish between active infection, past resolved infection, or false positivity. 1

Confirmatory Testing Algorithm

Order HCV RNA (Nucleic Acid Test)

• HCV RNA testing is the definitive test to confirm current infection and must be performed on all patients with reactive HCV antibody 1
• Use an FDA-approved qualitative or quantitative HCV RNA assay with detection sensitivity ≤25 IU/mL 1, 2
• Ideally, this should be reflexed automatically from the same blood sample used for antibody testing to avoid delays and loss to follow-up 1, 2, 3

Interpretation of HCV RNA Results

If HCV RNA is Detected (Positive):

• This confirms current active HCV infection requiring treatment 1, 2
• Proceed immediately to:
  • Quantitative HCV RNA testing (if qualitative test was done initially) 1
  • HCV genotyping/subgenotyping (genotype 1a/1b determination) prior to treatment 1
  • Assessment of liver disease severity and fibrosis staging 1
  • Screen for hepatitis B (HBsAg and anti-HBc) before initiating HCV treatment, as HBV reactivation can occur with HCV direct-acting antivirals 4, 5

If HCV RNA is Not Detected (Negative):

• This indicates either past resolved infection or false positive antibody test 1, 6
• No further testing is required in most cases 6
• Reassure the patient they are not currently infected and not infectious 6
• Note that 15-25% of older adults (>45 years) who acquire HCV spontaneously clear the infection 1, 6

Fibrosis Assessment (If HCV RNA Positive)

Non-invasive fibrosis assessment is essential before treatment decisions:

• Calculate FIB-4 score: age (years) × AST (IU/L) / [platelet count (10⁹/L) × √ALT (IU/L)] 1
  • FIB-4 <1.45: negative predictive value of 90% for advanced fibrosis 1
  • FIB-4 >3.25: positive predictive value of 65% for advanced fibrosis 1
• Calculate APRI: (AST/upper limit of normal) × 100 / platelet count (10⁹/L) 1
  • APRI >1.5: suggests significant fibrosis 1
  • APRI >2: suggests cirrhosis 1
• If advanced fibrosis is suspected, consider transient elastography (FibroScan) or additional testing 1, 7

Special Considerations for Elderly Patients

Important caveats in this population:

• If there was potential HCV exposure within the past 6 months, repeat HCV RNA testing even if initially negative, as acute infection may show transient RNA negativity 1, 6
• If the patient is immunocompromised, HCV RNA testing is particularly important as antibody development may be delayed or absent 1, 2
• Review for clinical signs of liver disease (jaundice, ascites, hepatomegaly, spider angiomata, elevated transaminases) 6

Treatment Considerations (If Active Infection Confirmed)

Modern treatment is highly effective and well-tolerated:

• Pangenotypic direct-acting antivirals are first-line for non-cirrhotic or compensated cirrhosis (Child-Pugh A) patients 7, 8
• Treatment options include sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks 7
• Patients with cirrhosis, comorbidities, or HIV/HBV coinfection should be referred to hepatology 7
• The goal is sustained virologic response (SVR), which prevents complications including cirrhosis, hepatocellular carcinoma, and death 1

Common Pitfalls to Avoid

• Never rely on antibody testing alone to diagnose active HCV infection—RNA testing is mandatory 1, 2
• Do not delay RNA testing waiting for genotype results; genotyping should only be done after confirming active infection 1, 7
• Do not assume positive antibody means active infection—many elderly patients have cleared the virus spontaneously 1, 6
• Always screen for hepatitis B before starting HCV treatment to prevent potentially fatal HBV reactivation 4, 5