What is the initial evaluation of hepatitis C?

Initial Evaluation of Hepatitis C

The initial evaluation of hepatitis C should begin with anti-HCV antibody testing as the first-line diagnostic test, followed by HCV RNA testing to confirm active infection if antibody testing is positive. 1, 2

Diagnostic Testing Algorithm

Step 1: Screening Test

• Anti-HCV antibody testing using an FDA-approved enzyme immunoassay (EIA) is the recommended initial screening test for HCV infection 1, 2
• In cases of suspected acute hepatitis C or in immunocompromised patients, HCV RNA testing should be included in the initial evaluation alongside antibody testing 1

Step 2: Confirmation of Active Infection

• If anti-HCV antibodies are detected, HCV RNA testing should be performed using a sensitive molecular method with a lower limit of detection <15 IU/ml 1, 2
• A positive anti-HCV test with positive HCV RNA indicates current (active) HCV infection requiring medical evaluation 2
• A positive anti-HCV test with negative HCV RNA indicates either past resolved infection or false positive antibody test 2
• Anti-HCV positive, HCV RNA negative individuals should be retested for HCV RNA 3 months later to confirm true convalescence 1

Step 3: Additional Testing After Confirmed HCV Infection

• Quantitative HCV RNA testing should be performed prior to treatment initiation to establish baseline viral load 2
• HCV genotype testing is necessary to determine the appropriate treatment regimen and duration, as well as to predict likelihood of response 2
• Assessment of liver fibrosis is essential to determine the urgency of treatment, using either liver biopsy or non-invasive testing 3

Laboratory Evaluation

• Complete blood count with platelets to assess for thrombocytopenia, which may suggest advanced liver disease 4
• Liver function tests including ALT, AST, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time/INR 4
• Hepatitis B serology (HBsAg, anti-HBs, anti-HBc) to rule out co-infection 1, 4
• HIV testing, as co-infection affects treatment decisions 1
• Assessment of renal function with blood urea nitrogen and creatinine 1

Clinical Assessment

• Evaluate for risk factors for HCV acquisition: history of injection drug use, blood transfusion prior to 1992, unsafe injection practices, occupational exposures, and other high-risk behaviors 4
• Assess for symptoms of liver disease: fatigue, jaundice, abdominal pain, nausea, dark urine, or clay-colored stools 4
• Physical examination should focus on signs of chronic liver disease or cirrhosis: jaundice, spider angiomata, palmar erythema, hepatomegaly, splenomegaly, ascites, or peripheral edema 4

Interpretation of Test Results

Diagnostic Scenarios

• Positive anti-HCV + Positive HCV RNA: Current active HCV infection requiring evaluation for treatment 2
• Positive anti-HCV + Negative HCV RNA: Past resolved infection or false positive; retest HCV RNA in 3 months 1
• Negative anti-HCV + Clinical suspicion of acute HCV: Test for HCV RNA, as antibodies may not be detectable in early infection 1

Common Pitfalls and Caveats

• False-negative anti-HCV results can occur during early acute infection (window period) and in severely immunocompromised patients 1
• Anti-HCV antibodies persist after viral clearance (spontaneous or treatment-induced), so antibody testing alone cannot distinguish between current and past infection 1
• Brief periods of undetectable HCV RNA may occur during acute infection, so a single negative HCV RNA test does not definitively rule out infection in suspected acute cases 1
• The diagnosis of chronic hepatitis C can only be made after 6 months of infection, as spontaneous viral clearance is rare beyond this time period 1