What are the diagnostic steps and treatment options for Hepatitis B (HBV) infection?

Hepatitis B Diagnosis

Screen all at-risk individuals with HBsAg, and if positive, confirm chronic infection with total anti-HBc (absence of IgM anti-HBc) and HBV DNA measurement—persistence of HBsAg beyond 6 months or de novo detection with compatible clinical factors establishes chronic hepatitis B. 1

Initial Screening Approach

• Screen high-risk populations including foreign-born individuals from areas with HBV prevalence ≥2%, persons who inject drugs, men who have sex with men, household/sexual contacts of HBsAg-positive persons, HIV-positive individuals, pregnant women, and those requiring immunosuppressive therapy 1
• Order HBsAg as the primary screening test—a positive result indicates active HBV infection (acute or chronic) 1
• All HBsAg-positive persons are infectious and capable of transmitting HBV via blood/serum or sexual contact 1

Distinguishing Acute from Chronic Infection

Acute Hepatitis B

• Positive HBsAg plus positive IgM anti-HBc (without total anti-HBc alone) confirms acute infection 1
• Isolated IgM anti-HBc may appear during the "window period" between HBsAg disappearance and anti-HBs development, particularly in severe/fulminant hepatitis 1, 2
• Follow these patients with repeat HBsAg, anti-HBc, and anti-HBs testing in 3-6 months to confirm recovery 1, 2

Chronic Hepatitis B

• Persistence of HBsAg beyond 6 months after acute hepatitis B establishes chronic infection 1
• De novo HBsAg detection with compatible clinical/epidemiologic factors is sufficient for diagnosis without waiting 6 months 1
• Positive total anti-HBc without IgM anti-HBc distinguishes chronic from acute infection 1
• Absence of IgM anti-HBc confirms chronic rather than acute disease 1

Comprehensive Initial Evaluation After Diagnosis

Essential Serological Tests

• HBsAg and anti-HBs: Distinguish active infection from immunity 1, 2
• Total anti-HBc and IgM anti-HBc: Differentiate acute, chronic, or resolved infection 1, 2
• HBeAg and anti-HBe: Essential for determining phase of chronic infection and replication status 1
• HBV DNA quantification: Essential for diagnosis, establishing infection phase, treatment decisions, and monitoring 1

Disease Severity Assessment

• Obtain AST, ALT, GGT, alkaline phosphatase, bilirubin, albumin, gamma globulins, complete blood count, and prothrombin time to assess liver disease severity 1
• Perform abdominal ultrasound in all patients at initial evaluation 1
• Consider transient elastography instead of liver biopsy for assessing fibrosis extent, though results may be confounded by severe inflammation with high ALT 1
• Liver biopsy is recommended but not mandatory in patients with intermittent or persistent ALT elevations to evaluate inflammation and fibrosis 1

Additional Testing

• HBV genotype: Not necessary initially but useful for interferon therapy selection and HCC risk assessment 1
• Serum HBsAg quantification: Useful particularly in HBeAg-negative chronic infection and for interferon-treated patients 1
• Screen for coinfections: Test for HDV, HCV, and HIV in at-risk individuals 1
• Test for anti-HAV antibodies: Vaccinate if negative 1
• Exclude other liver diseases: Rule out alcoholic, autoimmune, and metabolic liver disease 1

Special Serological Patterns

Resolved Infection

• Negative HBsAg, positive anti-HBs, and positive total anti-HBc (or anti-HBc alone) indicates resolved infection 1, 2
• Positive anti-HBs without anti-HBc indicates vaccine-induced immunity rather than past infection 1, 2

Isolated Anti-HBc

• Predominantly IgG anti-HBc alone usually indicates prior infection with spontaneous recovery 1
• May indicate occult hepatitis B, especially in immunocompromised patients with unexplained ALT elevation 1, 2
• Measure HBV DNA to diagnose occult hepatitis B in this scenario 1, 2
• Repeat testing in 3-6 months for patients with indeterminate results 2

Hepatocellular Carcinoma Screening

• Perform baseline ultrasound at initial encounter in all HBsAg-positive persons aged 20 years and older 1
• Screen all patients regardless of age, as younger patients can develop HCC despite peak risk after age 40 1
• Delayed HCC diagnosis limits therapeutic options and worsens prognosis 1

Critical Clinical Actions

Linkage to Care

• Refer all HBsAg-positive persons to a specialist or experienced primary care provider for hepatitis B management 1
• Specialists provide more complete evaluation and appropriate antiviral treatment compared to general primary care 1

Contact Management

• Test all first-degree relatives and sexual partners for HBsAg, anti-HBs, and anti-HBc 1
• Vaccinate all negative contacts immediately 1

Patient Counseling

• Counsel on transmission prevention and alcohol abstinence 1
• Recommend complete alcohol abstinence as it adversely affects disease progression 1

Common Pitfalls

• False-negative anti-HBs can occur in immunocompromised patients despite true immunity 2
• The "window period" may show negative HBsAg but positive IgM anti-HBc during acute infection 2
• Aminotransferase levels are unreliable for assessing disease activity post-transplant or in chronic infection 1
• Anti-HBs levels decline over time after vaccination but most individuals retain immune memory 2
• Approximately 5% of vaccinated individuals do not develop anti-HBs after standard vaccination 1