What is the recommended approach for a hepatitis workup and treatment?

Recommended Approach for Hepatitis Workup and Treatment

The recommended approach for hepatitis workup should begin with comprehensive serologic testing for hepatitis A, B, C, and D viruses, followed by targeted treatment based on the specific viral etiology identified, with direct-acting antivirals for HCV and nucleos(t)ide analogues with high barrier to resistance for HBV being the first-line treatments. 1, 2

Initial Diagnostic Testing

Hepatitis B Testing

• Test for HBsAg, anti-HBs, and anti-HBc total antibodies as the initial panel for hepatitis B 1, 2
• If HBsAg is positive, additional markers including HBeAg, anti-HBe, and HBV DNA quantification should be ordered 1, 2
• Anti-HDV testing should be performed in all HBsAg-positive patients to rule out hepatitis D coinfection 1

Hepatitis C Testing

• Begin with HCV-antibody testing with reflex HCV RNA PCR testing as the initial screening for hepatitis C 1
• Confirm active infection with HCV RNA testing in antibody-positive patients 1
• Quantitative HCV-RNA testing is required prior to initiating antiviral therapy 1

Hepatitis A Testing

• Include hepatitis A antibody testing (IgM and total) to assess for acute infection or immunity 1

Additional Laboratory Testing

• Liver function tests (ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, prothrombin time/INR) 2
• Complete blood count to assess for thrombocytopenia (marker of portal hypertension) 2
• Renal function tests (BUN and creatinine) 2
• Alpha-fetoprotein (AFP) for screening for hepatocellular carcinoma in chronic hepatitis patients 2
• HIV testing due to shared risk factors and impact on management 2

Interpretation of Hepatitis B Serologic Patterns

• Acute HBV infection: positive HBsAg and IgM anti-HBc, negative anti-HBs 2
• Chronic HBV infection: positive HBsAg for >6 months, total anti-HBc, variable HBeAg, anti-HBe, and HBV DNA levels 2
• Past HBV infection (resolved): positive anti-HBs and total anti-HBc, negative HBsAg 2
• Vaccine-induced immunity: positive anti-HBs only, negative HBsAg and anti-HBc 2

Management Approach by Etiology

Hepatitis B Management

• Determine disease phase based on HBsAg, HBeAg, anti-HBe, HBV DNA, and ALT levels 1
• Base treatment decisions on HBV DNA levels, ALT levels, and liver disease severity 1, 2
• First-line agents are nucleos(t)ide analogues with high barrier to resistance (e.g., entecavir) 1, 3
• For compensated liver disease, entecavir 0.5 mg once daily is recommended 3
• For decompensated liver disease or lamivudine-resistant cases, entecavir 1 mg once daily is recommended 3

Hepatitis C Management

• Direct-acting antivirals (DAAs) are recommended for all patients with chronic HCV infection 1, 2
• Pre-treatment testing for HBV is essential to assess risk of HBV reactivation 2
• Treatment duration is typically 8-12 weeks based on genotype, prior treatment, and cirrhosis status 2

Autoimmune Hepatitis Management

• Liver biopsy is recommended to confirm diagnosis and assess disease severity 1
• Corticosteroids (prednisone 1-2 mg/kg/d) are the initial treatment of choice 1
• Monitor IgG levels during treatment as they correlate with inflammatory activity 1

Special Considerations

• Management of HBV/HCV, HBV/HDV, or HIV coinfections requires careful consideration of viral interactions 1, 2
• Screen for HBV before immunosuppressive therapy; antiviral prophylaxis is required for high-risk patients 1, 2
• More intensive monitoring for complications including portal hypertension and hepatocellular carcinoma is required for patients with cirrhosis 1
• Hepatitis A and B vaccination is recommended for non-immune patients with chronic liver disease 2

Common Pitfalls to Avoid

• Do not miss testing for HDV in HBsAg-positive patients, as it significantly worsens prognosis 1
• Avoid using infliximab for immune checkpoint inhibitor-related hepatitis as it is contraindicated for hepatic immune-related adverse events 1
• Do not assume a negative HCV antibody test excludes infection in immunocompromised patients or those with recent exposure; consider HCV RNA testing 1
• Do not overlook the possibility of coexisting autoimmune hepatitis and viral hepatitis, especially in high-prevalence regions 1
• Do not discontinue entecavir treatment without close monitoring, as severe acute exacerbations of hepatitis B have been reported in patients who have discontinued therapy 3
• Monitor for lactic acidosis and severe hepatomegaly with steatosis, which have been reported with nucleoside analogue use, including entecavir 3