What tests are used to diagnose hepatitis?

Diagnostic Tests for Hepatitis

The essential diagnostic workup for hepatitis includes liver function tests, specific viral markers (serological and molecular), and specialized tests based on the suspected etiology of hepatitis. 1

Initial Laboratory Testing

Liver Function Tests

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) - indicate liver cell damage
• Gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase
• Bilirubin (total and direct)
• Serum albumin and gamma globulins
• Complete blood count and prothrombin time

Imaging

• Abdominal hepatic ultrasound is recommended in all patients with suspected hepatitis 2

Viral Hepatitis Testing

Hepatitis A

• Anti-HAV IgM: Diagnostic marker for acute infection
• Anti-HAV IgG: Indicates past infection and immunity 3

Hepatitis B

• Initial panel:
  • HBsAg (hepatitis B surface antigen): First marker to appear in acute infection; persistence >6 months indicates chronic infection
  • Anti-HBc (total and IgM): IgM indicates acute infection
  • Anti-HBs: Indicates recovery and immunity 2, 4
• Additional markers:
  • HBeAg and anti-HBe: Determine phase of infection and viral replication
  • HBV DNA quantification: Essential for diagnosis, determining infection phase, treatment decisions, and monitoring 2
  • HBsAg quantification: Useful for HBeAg-negative chronic infection and patients considered for interferon treatment 2
  • HBV genotype: May guide treatment selection and provide prognostic information 2

Hepatitis C

• Initial testing:
  • Anti-HCV antibody (enzyme immunoassay)
  • Positive results require confirmation with supplemental testing 2, 5
• Confirmatory and additional tests:
  • HCV RNA testing: Confirms active infection, quantifies viral load
  • Recombinant immunoblot assay (RIBA): Resolves false-positive EIA results in low-prevalence settings 5
  • HCV genotyping: Guides treatment decisions 5

Hepatitis D

• Only tested in HBsAg-positive patients (requires HBV for replication)
• Anti-HDV IgG: Simplest method for diagnosing delta infection 3
• Anti-HDV IgM and HDV RNA: Indicate active infection 6

Hepatitis E

• Anti-HEV IgM and IgG: For acute infection diagnosis
• HEV RNA: For confirmation of active infection
• HEV antigen: May be used for both acute and chronic infection diagnosis 2

Testing for Autoimmune Hepatitis

• Autoantibodies:
  • Antinuclear antibody (ANA)
  • Smooth muscle antibody (SMA)
  • Liver-kidney microsomal antibody (anti-LKM-1) 2, 1
• Additional markers:
  • Anti-soluble liver antigen/liver pancreas (SLA/LP)
  • Anti-liver cytosol type 1 (LC-1)
  • Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 2
• Other tests:
  • Serum IgG levels (typically elevated)
  • Liver biopsy (interface hepatitis) 2

Testing for Co-infections and Co-morbidities

• Screen for co-infections: HBV/HCV, HBV/HDV, HIV 2, 1
• Test for immunity to HAV in patients with chronic liver disease 7
• Evaluate for other causes of liver disease:
  • Alcoholic liver disease
  • Metabolic liver disease with steatosis or steatohepatitis
  • Other autoimmune conditions 2

Special Considerations

• Non-invasive fibrosis assessment:

  • Transient elastography (FibroScan)
  • Serum biomarkers of liver fibrosis 2

• Liver biopsy indications:

  • Unclear etiology after initial workup
  • Suspected autoimmune hepatitis
  • Assessment of disease severity/fibrosis
  • Steroid-refractory cases 1

• Occult HBV infection testing:

  • Consider in cryptogenic liver disease, especially if anti-HBc positive
  • Before immunosuppression due to potential for hepatitis flares
  • In solid organ transplant donors whose only serological marker of HBV infection is anti-HBc 2

Pitfalls and Caveats

• Serological testing alone for HEV is not sufficiently robust; combine with HEV NAT for accurate diagnosis 2
• Transient elastography results may be confounded by severe inflammation with high ALT levels 2
• False negative HEV RNA results can occur due to genetic polymorphisms 2
• Anti-HCV antibodies may take weeks to months to develop after infection; RNA testing is needed for early diagnosis 5
• Isolated total anti-HBc may indicate occult hepatitis B, especially in immunocompromised patients 2
• Diagnostic accuracy of non-invasive methods is better at excluding than confirming advanced fibrosis or cirrhosis 2

By following this comprehensive diagnostic approach, clinicians can accurately identify the type and stage of hepatitis, which is crucial for appropriate management and treatment decisions.