What hepatitis labs should be ordered for a patient with elevated liver enzymes?

Hepatitis Laboratory Workup for Elevated Liver Enzymes

Order hepatitis B surface antigen (HBsAg) and hepatitis C antibody (with reflex PCR if positive) as part of the core viral hepatitis screen for all patients with elevated liver enzymes. 1

Core Viral Hepatitis Panel

The standard liver etiology screen for elevated liver enzymes must include:

• Hepatitis B surface antigen (HBsAg) - identifies active hepatitis B infection 1
• Hepatitis C antibody - with automatic follow-on PCR testing if antibody is positive to confirm active infection 1

These two tests form the essential viral hepatitis screening component and should be ordered routinely for all patients with abnormal liver enzymes, as viral hepatitis represents one of the few immediately treatable causes of liver disease identified in only 1.3% of cases but requiring urgent intervention. 1

Extended Viral Hepatitis Testing Based on Clinical Context

For Marked Transaminase Elevations (ALT >1000 U/L)

Consider additional acute viral hepatitis serologies: 1, 2

• Hepatitis A IgM - for acute hepatitis A 1
• Hepatitis E IgM - particularly relevant in travelers or those from endemic areas 1
• Cytomegalovirus (CMV) serology - especially in immunocompromised patients 1

For Patients with HIV or High-Risk Populations

• Anti-hepatitis D (HDV) antibody - indicated for patients from countries where HDV is common or those with injection drug use history 1
• HBV DNA quantification - if HBsAg positive or if HIV coinfection present, as HIV patients can have occult HBV with negative HBsAg but positive anti-HBc 1
• Anti-HBc (hepatitis B core antibody) - particularly in HIV-positive patients to detect occult hepatitis B 1

Geographic and Risk-Based Considerations

Hepatitis delta quantification should be added in high-prevalence areas or patients with risk factors for HDV coinfection. 1

Country of origin (not ethnic group) is the strongest predictor of viral hepatitis, making travel and immigration history critical for determining which additional viral studies to order. 1

Complete Initial Laboratory Panel

Beyond viral hepatitis markers, the comprehensive workup should simultaneously include: 1, 2

• Complete blood count with differential - to evaluate thrombocytopenia (suggests advanced fibrosis) and assess leukocytosis 2
• Complete metabolic panel - including bilirubin, albumin, ALT, AST, ALP, GGT 1, 2
• Prothrombin time/INR - assesses synthetic liver function 1
• Autoimmune markers: anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins 1
• Iron studies: simultaneous serum ferritin and transferrin saturation 1
• Abdominal ultrasound - to assess liver parenchyma, biliary tract, and exclude structural abnormalities 1, 2

Critical Pitfalls to Avoid

Do not simply repeat the same abnormal liver tests without pursuing the underlying etiology, as 75% of abnormal liver enzymes remain abnormal at 2 years, indicating persistent pathology requiring diagnosis. 1

In HIV-positive patients, always test both HBsAg AND anti-HBc, as occult HBV infection can occur with high HBV DNA levels despite negative HBsAg. 1

Elevated liver enzymes in HIV/HBV coinfection may be multifactorial, caused by HBV itself, HAART medications, or opportunistic infections like CMV, requiring broader infectious workup. 1

Timing and Follow-Up

For patients with positive viral hepatitis markers (HBsAg or HCV antibody positive with confirmatory PCR), immediate referral to hepatology is indicated for treatment consideration, as these represent immediately treatable causes of liver disease. 1

Monitor ALT every 3-6 months for chronic hepatitis B patients not meeting treatment criteria, with more frequent monitoring if ALT becomes elevated. 1

For HCV antibody-positive patients, PCR confirmation is mandatory to distinguish active infection (requiring treatment) from resolved infection. 1