What are the initial tests and treatment options for a hepatitis panel workup, including hepatitis A (Hep A), hepatitis B (Hep B), hepatitis C (Hep C), and hepatitis D (Hep D) infections?

Comprehensive Hepatitis Panel Workup

A complete hepatitis panel workup should include testing for hepatitis A, B, C, and D viruses, with specific serologic markers to determine acute versus chronic infection status, and viral load testing when indicated for treatment decisions. 1

Initial Hepatitis Serologic Testing

Hepatitis B Testing

• HBsAg (Hepatitis B surface antigen): Indicates current HBV infection (acute or chronic) 1
• Anti-HBs (Hepatitis B surface antibody): Indicates immunity from vaccination or recovery from past infection 1
• Anti-HBc total (Hepatitis B core total antibodies): Indicates previous or ongoing HBV infection 1
• Anti-HBc IgM: Indicates acute or recent HBV infection (positive for approximately 6 months) 1, 2
• HBeAg (Hepatitis B e antigen): Marker of high viral replication 1
• Anti-HBe (Hepatitis B e antibody): Usually indicates lower viral replication 1
• HBV DNA quantitative (viral load): Assesses level of viral replication; essential for treatment decisions 1

Hepatitis C Testing

• Anti-HCV antibody: Initial screening test for HCV infection 1
• HCV RNA quantitative (viral load): Confirms active infection if antibody is positive 1

Hepatitis A Testing

• Anti-HAV IgG: Indicates past infection or vaccination 3
• Anti-HAV IgM: Indicates acute HAV infection 3

Hepatitis D Testing (for HBsAg-positive patients)

• Anti-HDV total antibodies: Screening test for HDV coinfection or superinfection 1
• Anti-HDV IgM: Indicates acute HDV infection 1
• HDV RNA: Confirms active HDV replication 1, 4

Additional Laboratory Testing

• Liver function tests: ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, prothrombin time/INR 1
• Complete blood count: Assess for thrombocytopenia (marker of portal hypertension) 1
• Renal function tests: BUN, creatinine 1
• Alpha-fetoprotein (AFP): Screening for hepatocellular carcinoma in chronic hepatitis patients 1
• HIV testing: Recommended due to shared risk factors and impact on management 1

Interpretation of Hepatitis B Serologic Patterns

Acute HBV Infection

• Positive: HBsAg and IgM anti-HBc
• Negative: Anti-HBs 1

Chronic HBV Infection

• Positive: HBsAg for >6 months, total anti-HBc
• Negative: IgM anti-HBc (usually)
• Variable: HBeAg, anti-HBe, HBV DNA levels 1

Past HBV Infection (Resolved)

• Positive: Anti-HBs and total anti-HBc
• Negative: HBsAg 1

Vaccine-Induced Immunity

• Positive: Anti-HBs only
• Negative: HBsAg and anti-HBc 1

Treatment Considerations

Hepatitis B Treatment

• Antiviral therapy indications: Based on HBV DNA levels, ALT levels, and liver disease severity 1
• First-line agents: Nucleos(t)ide analogues with high barrier to resistance 4
• Treatment goals: HBV DNA suppression, ALT normalization, HBeAg seroconversion, and ideally HBsAg loss 1, 4

Hepatitis C Treatment

• Direct-acting antivirals (DAAs): Recommended for all patients with chronic HCV infection 1
• Pre-treatment testing: HBV testing required before starting HCV treatment due to risk of HBV reactivation 5, 6
• Treatment duration: Typically 8-12 weeks based on genotype, prior treatment, and cirrhosis status 1

Hepatitis D Treatment

• Treatment options: Limited compared to HBV and HCV, but new therapies are emerging 4
• Pegylated interferon: Traditional therapy with limited efficacy 4
• Bulevirtide: Recently approved therapy for chronic HDV 4

Special Considerations

HBV Reactivation Risk

• Screen for HBV before immunosuppressive therapy: Test HBsAg and anti-HBc 1
• Antiviral prophylaxis: Required for high-risk patients (HBsAg-positive) and some moderate-risk patients (HBsAg-negative, anti-HBc-positive) receiving immunosuppressive therapy 1

Vaccination Recommendations

• Hepatitis A vaccination: Recommended for all patients with chronic liver disease who lack immunity 1, 3, 7
• Hepatitis B vaccination: Recommended for non-immune patients with chronic liver disease 1, 3, 7
• Early vaccination: Important as response rates decline with advancing liver disease 3, 7

Coinfection Management

• HBV/HCV coinfection: Test for HBV before HCV treatment; monitor for HBV reactivation during and after HCV therapy 1, 5
• HBV/HDV coinfection: More severe disease progression; requires specialized management 1, 4
• HIV coinfection: Requires coordinated care with HIV specialists; affects treatment decisions 1

Common Pitfalls to Avoid

• Missing the "window period": During acute HBV infection, there may be a period when HBsAg has disappeared but anti-HBs is not yet detectable; IgM anti-HBc is crucial for diagnosis during this period 1, 2
• Misinterpreting isolated anti-HBc: May indicate occult HBV infection, resolved infection with waned antibodies, or false-positive result; requires careful evaluation 1
• Failing to screen for HBV before HCV treatment: Can lead to HBV reactivation with potentially severe consequences 5
• Inadequate monitoring of patients with chronic viral hepatitis: Regular monitoring for disease progression and hepatocellular carcinoma is essential 1