What are the initial steps in diagnosing and managing a patient presenting with hepatitis, including laboratory tests and treatment options?

Hepatitis Diagnosis, Laboratory Evaluation, and Management

Initial Diagnostic Approach

For any patient presenting with suspected hepatitis, immediately measure prothrombin time/INR and carefully assess mental status—if INR ≥1.5 with any altered mentation, diagnose acute liver failure and transfer to ICU immediately. 1

Critical History Elements

• Transmission risk factors must include sexual contacts, injection drug use history, blood transfusion history (especially pre-1992), travel to endemic regions, family history of HBV/hepatocellular carcinoma, and occupational needle-stick exposures 2, 3

• Symptom assessment should document duration and severity of jaundice, fatigue intensity, right upper quadrant pain, nausea/vomiting, fever presence, dark urine, and clay-colored stools 2

• Medication review requires detailed accounting of all prescription drugs, over-the-counter medications, herbal supplements, and acetaminophen use 1, 4

Physical Examination Findings

• Assess for acute versus chronic disease: absence of stigmata of chronic liver disease (spider angiomata, palmar erythema, splenomegaly) suggests acute hepatitis 1, 5

• Liver size matters: inability to palpate or percuss the liver suggests massive hepatocyte loss in acute liver failure; hepatomegaly may indicate viral hepatitis, malignant infiltration, or Budd-Chiari syndrome 1

• Right upper quadrant tenderness is variably present and nonspecific 1

Essential Laboratory Testing

Immediate Initial Panel

All patients require this comprehensive initial workup: 1, 2, 3, 6

• Complete blood count with platelets (cytopenias suggest portal hypertension) 1, 3

• Prothrombin time/INR (critical for identifying acute liver failure) 1, 3, 6

• Liver function tests: AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin 1, 2, 3, 6

• Renal function: creatinine, blood urea nitrogen 1

• Glucose (hypoglycemia indicates severe hepatic dysfunction) 1

• Electrolytes: sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate 1

• Arterial blood gas and arterial lactate if acute liver failure suspected 1

Viral Hepatitis Serologic Panel

Mandatory viral testing includes: 1, 2, 3, 6

• Hepatitis A: anti-HAV IgM (acute infection) and IgG anti-HAV (immunity status) 1, 6

• Hepatitis B core panel:

  • HBsAg (active infection marker) 3, 6, 7, 8
  • Anti-HBc total (current or past infection) 3, 6
  • Anti-HBc IgM (distinguishes acute from chronic—positive in acute, negative in chronic) 3, 6
  • Anti-HBs (recovery or vaccination) 6

• Hepatitis B replication markers:

  • HBeAg (high viral replication) 1, 3, 6
  • Anti-HBe (lower replication phase) 1, 3, 6
  • Quantitative HBV DNA (essential for treatment decisions) 1, 3, 6

• Hepatitis C: anti-HCV antibody 1, 3, 6

• Hepatitis D: anti-HDV in injection drug users or endemic area exposure 6

• Hepatitis E: anti-HEV 1

Mandatory Coinfection Screening

• HIV testing required for all HBsAg-positive patients because coinfection accelerates liver disease and alters treatment approach 3, 6

• Anti-HCV testing necessary to detect hepatitis C coinfection which significantly worsens prognosis 3, 6

Additional Critical Tests

• Ceruloplasmin level (Wilson disease screening) 1

• Serum iron, ferritin, transferrin saturation (hemochromatosis) 4

• Autoimmune markers if indicated 1

• Acetaminophen level and toxicology screen 1

• Pregnancy test in females 1

• Ammonia level (arterial preferred) 1

• Alpha-fetoprotein for hepatocellular carcinoma screening 3, 6

• Right upper quadrant ultrasound for all HBsAg-positive patients age ≥20 years 3, 6

Interpretation of Hepatitis B Serologic Patterns

• Acute HBV infection: HBsAg positive + IgM anti-HBc positive 6

• Chronic HBV infection: HBsAg positive >6 months + total anti-HBc positive + IgM anti-HBc negative 3, 6

• Past infection with immunity: HBsAg negative + anti-HBs positive + total anti-HBc positive 6

• Vaccine-induced immunity: HBsAg negative + anti-HBs positive + total anti-HBc negative 6

• Window period pitfall: Both HBsAg and anti-HBs may be negative—IgM anti-HBc is positive during this period 6

Management Based on Hepatitis B Status

HBeAg-Positive Chronic Hepatitis B

Treatment criteria: 1, 2

• ALT >2× ULN with HBV DNA >20,000 IU/mL for 3-6 months: Consider treatment immediately 1

• ALT 1-2× ULN with HBV DNA >20,000 IU/mL for 3-6 months OR age >40 years: Consider liver biopsy; treat if moderate/severe inflammation or significant fibrosis 1

• Normal ALT: Monitor ALT every 3-6 months, HBeAg status every 6-12 months 1, 2

HBeAg-Negative Chronic Hepatitis B

Treatment threshold is lower: 1, 6

• HBV DNA ≥2,000 IU/mL (not 20,000) with elevated ALT warrants treatment consideration 1, 6

• Normal ALT with HBV DNA <2,000 IU/mL: Test ALT every 3 months for first year to confirm inactive carrier state, then every 6-12 months 1

Critical Treatment Indications

Immediate treatment required for: 1

• Jaundice or decompensated cirrhosis regardless of HBV DNA or ALT levels 1

• Cirrhosis with any detectable HBV DNA (lower thresholds apply) 1

Treatment Options

• Nucleos(t)ide analogues are primary treatment for chronic hepatitis B 2

• Pegylated interferon in selected cases 2

• For hepatitis C: Ledipasvir/sofosbuvir regimens based on genotype, cirrhosis status, and treatment history 7, 8

Monitoring Protocol

For Untreated Chronic Hepatitis B Patients

• ALT monitoring every 3-6 months 1, 2, 3, 6

• HBV DNA every 6-12 months 3, 6

• HBeAg/anti-HBe status annually if initially HBeAg-positive 3, 6

For Cirrhotic Patients

• Hepatocellular carcinoma surveillance with ultrasound every 6 months 1, 2, 6

• More frequent monitoring of all parameters 6

Essential Preventive Measures

• Hepatitis A vaccination: Two doses 6-18 months apart for all anti-HAV negative patients with chronic hepatitis B 1, 2, 3

• Contact management: Identify and vaccinate all sexual and household contacts who are anti-HBs negative 3

• Alcohol abstinence counseling (accelerates progression to cirrhosis) 2, 3

• Transmission prevention counseling: Safe sex practices, avoid sharing personal items 3

Critical Pitfalls to Avoid

• Missing the window period: Isolated anti-HBc positivity requires follow-up testing 6

• Underestimating HBeAg-negative disease: Lower HBV DNA levels (≥2,000 IU/mL, not 20,000) still cause progressive disease 1, 6

• Ignoring age-adjusted ALT thresholds: Upper limit of normal should be 30 U/L for men and 19 U/L for women—patients near "normal" may have significant histology, especially if age >40 1

• Failing to test for HBV before starting HCV treatment: HBV reactivation can cause fulminant hepatitis and death 7, 8

• Missing family history implications: Positive family history of cirrhosis/HCC warrants treatment even without advanced fibrosis 3