What are the diagnostic and treatment approaches for Hepatitis C (HCV)?

Diagnostic and Treatment Approaches for Hepatitis C (HCV)

The diagnosis of Hepatitis C requires initial anti-HCV antibody testing followed by confirmatory HCV RNA testing to identify active infection, while treatment should be initiated with direct-acting antivirals (DAAs) to achieve viral eradication and prevent complications of liver disease. 1

Diagnostic Algorithm for HCV

Initial Screening

• Anti-HCV antibodies are the first-line diagnostic test for HCV infection 1
• Screening strategies should be tailored to local epidemiology and risk factors 1
• Rapid diagnostic tests (RDTs) using serum, plasma, fingerstick whole blood, or oral fluid can be used as alternatives to traditional enzyme immunoassays 1
• Dried blood spots can be used when venipuncture is challenging 1

Confirmatory Testing

1. If anti-HCV antibodies are detected:

   • HCV RNA testing should be performed using a sensitive molecular method 1
   • Alternatively, HCV core antigen can be used when RNA testing is unavailable or unaffordable 1
   • HCV core antigen is slightly less sensitive than HCV RNA (lower limit of detection equivalent to 500-3000 HCV RNA IU/ml) 1

2. Special situations:

   • In suspected acute hepatitis C or immunocompromised patients, HCV RNA testing should be part of initial evaluation 1
   • Anti-HCV positive, HCV RNA negative individuals should be retested for HCV RNA 3 months later to confirm clearance 1

Reflex Testing

• Reflex testing (automatic HCV RNA testing on the same sample when anti-HCV is positive) substantially increases the proportion of patients who receive complete diagnostic evaluation 1

Treatment Approach

Goals of Therapy

• The primary goal is to cure HCV infection to prevent complications including:
  • Hepatic necroinflammation and fibrosis
  • Cirrhosis and decompensation
  • Hepatocellular carcinoma (HCC)
  • Extrahepatic manifestations
  • Death 1

Treatment Endpoint

• Sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion 1
• SVR corresponds to definitive cure in >99% of cases 1

Pre-treatment Assessment

1. Liver disease severity evaluation:

   • Clinical examination
   • Laboratory tests
   • Non-invasive fibrosis assessment (e.g., elastography)
   • Liver biopsy when indicated 1

2. Viral factors:

   • HCV RNA quantification
   • HCV genotype/subtype determination 1

Important Considerations

HBV Coinfection Risk

• Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before initiating HCV treatment 2
• HBV reactivation can occur during or after HCV treatment, potentially leading to fulminant hepatitis, liver failure, and death 2
• Monitor patients with serologic evidence of HBV for reactivation during and after HCV treatment 2

Monitoring During Treatment

• Regular assessment of treatment adherence, side effects, and drug-drug interactions
• HCV RNA testing to confirm viral suppression
• Monitoring for adverse events specific to the chosen regimen

Post-treatment Follow-up

• Confirm SVR at 12 or 24 weeks post-treatment
• Continued surveillance for HCC in patients with advanced fibrosis or cirrhosis, as risk remains despite viral clearance 1

Common Pitfalls to Avoid

1. Failing to confirm active infection with HCV RNA testing in antibody-positive patients
2. Missing HCV infection in immunocompromised patients who may have false-negative antibody tests
3. Not testing for HBV coinfection before initiating HCV treatment
4. Assuming normal liver enzymes rule out significant liver disease
5. Discontinuing HCC surveillance in cirrhotic patients who achieve SVR

By following this structured approach to diagnosis and treatment, HCV infection can be effectively identified and managed, significantly reducing morbidity and mortality associated with chronic hepatitis C.