Is an elevated Alanine Transaminase (ALT) level alone a justification for ordering Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) laboratory tests?

From the Guidelines

Elevated ALT alone is not sufficient justification for HBV and HCV testing in all cases, and testing should be guided by risk factors, clinical context, and the degree of ALT elevation. For patients with persistently elevated ALT (typically >1.5 times upper limit of normal on multiple occasions), or those with risk factors such as history of injection drug use, blood transfusions before 1992, birth in endemic regions, or high-risk sexual behaviors, HBV and HCV testing is appropriate 1. The recommended initial tests include HBsAg, anti-HBc, anti-HBs for hepatitis B, and anti-HCV antibody for hepatitis C. If the anti-HCV is positive, follow up with HCV RNA testing to confirm active infection.

• ALT elevation can result from many conditions including medication effects, alcohol use, fatty liver disease, and other viral infections, so these should be considered in the differential diagnosis.
• The degree of ALT elevation can provide clues - viral hepatitis typically causes more significant elevations (often >10x ULN in acute cases) compared to non-alcoholic fatty liver disease or medication effects.
• Testing for viral hepatitis is relatively inexpensive and non-invasive, so there should be a low threshold for testing when clinical suspicion exists.
• According to the most recent study from 2022, patients with elevated HBV DNA level (>2,000 IU/mL) but normal or mildly elevated ALT level require careful evaluation of their degree of fibrosis to decide if they should undergo antiviral treatment or monitoring 1.
• The study also suggests that some patients who are presumed to be in the immune-tolerant phase will develop complications during follow-up, and that antiviral treatment can decrease this risk 1.
• Another study from 2020 recommends that patients commencing DAA-based treatment for hepatitis C should be tested for HBs antigen, anti-HBc antibodies and anti-HBs antibodies, and if HBs antigen is present, concurrent HBV nucleoside/nucleotide analogue therapy is indicated 1.

From the Research

Elevated ALT Levels and HBV/HCV Testing

• An elevated Alanine Transaminase (ALT) level can be a marker of severe liver disease with variable aetiologies and prognosis 2
• However, elevated ALT levels do not always confirm liver disease, and other causes such as choledocholithiasis, ischaemic hepatitis, and drug-induced liver injury (DILI) should be considered 2, 3
• Viral hepatitis, including Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV), is an important aetiology of elevated ALT levels, but it is not the only cause 2

Diagnostic Approach

• A diagnostic approach to elevated ALT levels should include a thorough diagnostic work-up, including routine laboratory tests, ultrasound of the abdomen, and potentially liver biopsy 3
• If aminotransferase levels are persistently more than twice the normal value, a biopsy is recommended to exclude serious pathology 3
• Non-invasive models, such as the AAF model, can be used to identify patients with chronic HBV infection who require antiviral therapy, even if they have normal ALT levels 4

HBV and HCV Testing

• HBV and HCV testing may be justified in patients with elevated ALT levels, especially if other causes have been ruled out 2, 5
• However, the decision to order HBV and HCV tests should be based on a thorough diagnostic work-up and consideration of other potential causes of elevated ALT levels 3, 6
• Patients with chronic HBV infection and normal ALT levels may still require antiviral therapy, and non-invasive models can be used to identify those who require treatment 4