How should I evaluate and manage acute and chronic hepatitis A, B, C, and E, including appropriate serologic testing, treatment options, vaccination, monitoring, and referral for advanced disease?

Management of Viral Hepatitis

Initial Evaluation and Serologic Testing

All patients with suspected viral hepatitis require immediate serologic testing to establish the specific viral etiology, assess disease activity, and determine immunity status to guide vaccination and treatment decisions. 1, 2

Hepatitis B Serologic Testing

• HBsAg is the primary marker for active HBV infection, with positivity for >6 months defining chronic infection 2
• Anti-HBc total indicates current or previous HBV infection and should be tested alongside HBsAg 2
• Anti-HBc IgM indicates acute infection when positive, distinguishing acute from chronic disease 2
• Anti-HBs indicates recovery from infection or successful vaccination 2
• HBeAg serves as a marker of high viral replication, while anti-HBe usually indicates lower viral replication 2
• HBV DNA quantification is essential for assessing viral replication, disease activity, and treatment decisions 2

Common serologic patterns:

• Acute HBV: HBsAg positive, IgM anti-HBc positive 2
• Chronic HBV: HBsAg positive for >6 months, total anti-HBc positive, IgM anti-HBc negative 2
• Past infection with immunity: HBsAg negative, anti-HBs positive, total anti-HBc positive 2
• Vaccine-induced immunity: HBsAg negative, anti-HBs positive, total anti-HBc negative 2

Hepatitis C Testing

• HCV antibody testing followed by HCV RNA quantification establishes active infection 3
• Calculate FIB-4 score to assess fibrosis without liver biopsy 3
• Genotype testing is no longer required for most treatment decisions with current pan-genotypic regimens 3

Coinfection Screening

All patients with viral hepatitis must be tested for coinfections that significantly impact prognosis and management:

• Anti-HCV to rule out HCV coinfection 2
• Anti-HDV in patients with injection drug use history or from endemic areas 2
• Anti-HIV in high-risk groups 2
• Anti-HAV IgG to determine immunity status, with vaccination recommended if negative 2

Baseline Laboratory Assessment

• Complete blood count with platelets to assess for cytopenias suggesting advanced disease 1
• Comprehensive liver function tests: ALT, AST, alkaline phosphatase, bilirubin, albumin, PT/INR 2
• Alpha-fetoprotein for baseline HCC screening 2
• Ultrasound for baseline evaluation in high-risk patients 2

Management of Chronic Hepatitis B

Because 15%-25% of persons with chronic HBV infection are at risk for premature death from cirrhosis and liver cancer, all patients must be evaluated soon after infection is identified by referral to or consultation with a physician experienced in chronic liver disease management. 3

Initial Evaluation

• Thorough history focusing on: risk factors for HIV/HCV coinfection, alcohol use, family history of HBV infection and liver cancer 3
• Laboratory assessment for: HBeAg, anti-HBe, HBV DNA levels, coinfection with HCV/HDV/HIV 3
• Schistosomiasis testing in persons from endemic areas where available, as it increases progression to cirrhosis and HCC 3

Treatment Indications

Treatment decisions are based on HBeAg status, HBV DNA levels, ALT elevation, and evidence of liver fibrosis: 1

• HBeAg-positive chronic hepatitis B: typically HBV DNA ≥20,000 IU/mL 2
• HBeAg-negative chronic hepatitis B: typically HBV DNA ≥2,000 IU/mL 2
• Inactive carrier state: HBV DNA <2,000 IU/mL 2

Treatment options include nucleos(t)ide analogues and pegylated interferon in selected cases 1

Monitoring for Untreated Chronic HBV

All patients with chronic HBV infection require lifelong monitoring, even those with normal aminotransferase levels 3:

• ALT every 3-6 months 1, 2
• HBV DNA every 6-12 months 2
• HBeAg/anti-HBe status annually 2
• Ultrasound for HCC surveillance every 6 months in high-risk patients (Asian men >40 years, Asian women >50 years, persons with cirrhosis, family history of HCC, Africans >20 years, HBV-infected persons >40 years with persistent/intermittent ALT elevation and/or high HBV DNA) 3

Preventive Measures for HBV-Positive Patients

To prevent transmission to others:

• Notify household, sex, and needle-sharing contacts for testing and vaccination 3
• Use condoms to protect nonimmune sex partners until vaccination and immunity documented 3
• Cover cuts and skin lesions, clean blood spills with bleach solution 3
• Refrain from donating blood, plasma, tissue, or semen 3
• Avoid sharing household articles (toothbrushes, razors, personal injection equipment) that could be contaminated with blood 3

To protect the liver from further harm:

• Avoid or limit alcohol consumption with referral for alcohol abuse treatment if needed 3
• Obtain hepatitis A vaccination (2 doses, 6-18 months apart) if chronic liver disease is present 3, 1

For HBsAg-positive pregnant women:

• Newborns must receive hepatitis B vaccine and hepatitis B immune globulin beginning at birth and complete the vaccine series 3

Management of Chronic Hepatitis C

Simplified Treatment Eligibility

Adults with chronic hepatitis C (any genotype) who have compensated cirrhosis (Child-Pugh A) and no prior hepatitis treatment are eligible for simplified treatment. 3

Patients NOT eligible for simplified treatment:

• Current or prior decompensated cirrhosis (CTP score ≥7) 3
• Prior hepatitis treatment 3
• End-stage renal disease (eGFR <30 mL/min/m²) 3
• HIV or HBsAg positive 3
• Current pregnancy 3
• Known or suspected HCC 3
• Prior liver transplantation 3

Pretreatment Assessment

• Calculate FIB-4 score and CTP score 3
• Ultrasound of the liver (within prior 6 months) to exclude HCC and subclinical ascites 3
• Medication reconciliation including over-the-counter drugs and herbal/dietary supplements 3
• Drug-drug interaction assessment using AASLD/IDSA guidance or University of Liverpool checker 3

On-Treatment Monitoring

Minimal monitoring is required for most patients: 3

• Monitor for hypoglycemia in patients taking diabetes medication 3
• Monitor INR for patients taking warfarin for subtherapeutic anticoagulation 3
• Patients should see a specialist if they develop worsening liver tests or jaundice 3

Assessment of Cure (SVR)

Assessment of quantitative HCV RNA and hepatic function panel are required 12 weeks or later following completion of therapy to confirm HCV RNA is undetectable (virologic cure) and transaminase normalization 3

For patients who do not achieve SVR:

• Evaluate for retreatment by a specialist in accordance with AASLD/IDSA guidance 3
• For patients unable to be retreated: assess for disease progression every 6-12 months with hepatic function panel, CBC, and INR 3

Management of Hepatitis A

Hepatitis A is self-limited and requires only supportive care, but vaccination is critical for prevention in at-risk populations 3

Vaccination recommendations:

• All patients with chronic liver disease should receive 2 doses of hepatitis A vaccine 6-18 months apart 3, 1
• Prevaccination testing for anti-HAV IgG is cost-effective in areas with higher local HAV prevalence and in populations with higher background exposure (older adults, foreign-born patients, African Americans, persons with chronic liver disease) 4
• Postvaccination serologic testing is recommended in patients with decompensated or advanced end-stage liver disease due to lower seroconversion rates 4

Management of Hepatitis E

Hepatitis E is typically self-limited in immunocompetent hosts but can cause severe disease in pregnant women and chronic infection in immunocompromised patients 1

Critical Pitfalls to Avoid

Failure to recognize the "window period" when both HBsAg and anti-HBs may be negative (IgM anti-HBc is positive during this period) 2

Misinterpreting isolated anti-HBc positivity requires follow-up testing 2

HBeAg-negative chronic hepatitis B can have lower HBV DNA levels but still cause progressive liver disease 2

Failure to test for coinfections, particularly in high-risk populations, can lead to missed diagnoses and inadequate management 2

Inadequate HCC surveillance in high-risk patients significantly impacts mortality 3