What initial investigations should be performed in a patient with suspected viral hepatitis?

Initial Investigations for Suspected Viral Hepatitis

Order a comprehensive hepatitis panel including HBsAg, hepatitis B surface antibody, hepatitis B core antibody (HBcAb IgG and IgM), and HCV antibodies, combined with liver function tests (ALT, AST, bilirubin, alkaline phosphatase, albumin, PT/INR) and a complete blood count with platelets. 1, 2, 3

Core Serologic Testing

The hepatitis panel must include:

• Hepatitis B surface antigen (HBsAg) to detect active HBV infection 1, 3
• Hepatitis B surface antibody to assess immunity 1
• Hepatitis B core antibody (HBcAb) IgG since isolated HBcAb IgG may still indicate chronic HBV infection 1
• HBcAb IgM specifically in patients presenting with acute viral hepatitis 1, 3
• Hepatitis C antibody (HCV Ab) for HCV screening 1, 3

Critical follow-up step: If HBsAg, HBcAb IgG, or HCV antibodies test positive, immediately confirm with quantitative viral load testing (HBV DNA or HCV RNA) to determine active viral replication and need for hepatologist referral. 1

Essential Liver Function Assessment

Obtain the following laboratory tests to assess hepatic injury and synthetic function:

• Aminotransferases: ALT (primary marker of hepatocellular injury) and AST 1, 3
• Cholestatic markers: Alkaline phosphatase and GGT 3
• Bilirubin to assess hepatic excretory function 1, 3
• Albumin to reflect hepatic synthetic function and chronicity 1, 3
• Prothrombin time/INR to evaluate coagulation and synthetic capacity 1, 3
• Platelet count as a surrogate marker for portal hypertension 1, 3

Additional Baseline Testing

• Complete blood count to assess for cytopenias suggesting advanced disease 3
• Blood urea nitrogen and creatinine for renal function assessment, as creatinine is an established prognostic marker in liver disease 1, 3

Expanded Testing for Marked Elevations

When ALT exceeds 1000 U/L, add serologies for:

• Hepatitis A virus (HAV IgM) 3
• Hepatitis E virus 3
• Cytomegalovirus 3

This broader panel helps identify acute viral causes that can present with severe hepatocellular injury. 3

Risk Factor Assessment

Document specific exposure history including:

• Sexual history and injection drug use 2
• Blood transfusion history, particularly before 1992 2
• Travel to endemic areas 2
• Family history of HBV infection and hepatocellular carcinoma 2
• Occupational exposures to blood or body fluids 2

Symptom Documentation

Assess and document:

• Duration and severity of jaundice 2
• Fatigue, malaise, and constitutional symptoms 2
• Abdominal pain location and character 2
• Nausea, vomiting, and anorexia 2
• Fever patterns 2
• Dark urine or clay-colored stools 2

Physical Examination Findings

Focus on:

• Skin examination for jaundice, spider angiomata, palmar erythema 2
• Abdominal examination for hepatomegaly, splenomegaly, ascites, and tenderness 2
• Vital signs including temperature and hemodynamic stability 2

Important Caveats

Beware of false-positive serologies: EBV infection can cause false-positive HAV IgM, ANA, and elevated total IgG, mimicking acute hepatitis A or autoimmune hepatitis. 4 Always correlate serologic results with clinical context and consider repeat testing if results are discordant with the clinical picture.

AFP has limited utility in acute hepatitis: While AFP may be checked if hepatocellular carcinoma is suspected, it lacks specificity and can be elevated in chronic HBV/HCV infection and other conditions. 3 Imaging findings are more definitive than AFP alone. 1

Autoimmune markers may be needed: If viral serologies are negative and transaminases remain markedly elevated, consider testing serum IgG, ANA, anti-smooth muscle antibody (ASMA), and anti-LKM antibodies to evaluate for autoimmune hepatitis. 3