Management of Abnormal Liver Function Tests

Initial Assessment and Management

The American Gastroenterological Association recommends stopping all potentially hepatotoxic medications if ALT/AST exceeds 5× the upper limit of normal (ULN), or if any elevation occurs with jaundice or elevated bilirubin, regardless of the absolute enzyme level 1
Obtain a complete panel including ALT, AST, alkaline phosphatase (ALP), GGT, total and direct bilirubin, albumin, and prothrombin time/INR to determine the pattern and severity of liver injury 2

Mild elevations are defined as <5× ULN, moderate elevations as 5-10× ULN, severe elevations as >10× ULN, and life-threatening elevations as >20× ULN 2
Monitor liver enzymes weekly until normalization for mild elevations, every 2-3 days until stable or improving for moderate elevations, and every 1-2 days for severe elevations 1, 2

Review all medications, including prescription drugs, over-the-counter medications, herbal supplements, and illicit drugs, and quantify alcohol intake using AUDIT-C scoring tool 3, 2
Assess metabolic syndrome features, such as central obesity, hypertension, diabetes, and dyslipidemia, and identify risk factors for viral hepatitis, including country of birth, injecting drug use, and travel history 3

Perform a standard panel, including hepatitis B surface antigen (HBsAg), hepatitis C antibody, serum ferritin and transferrin saturation, immunoglobulin G levels and autoantibodies, and anti-mitochondrial antibody if cholestatic pattern is present 3, 2

For mild elevations, monitor liver enzymes weekly until normalization and discontinue potentially hepatotoxic medications and alcohol 1, 2
For moderate elevations, monitor liver enzymes every 2-3 days until stable or improving, and consider holding immune checkpoint inhibitor treatment temporarily 1, 2
For severe elevations, monitor liver enzymes every 1-2 days, and permanently discontinue immune checkpoint inhibitor treatment if hepatotoxicity is suspected 1, 2

Refer to hepatology for hepatitis B or C, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, haemochromatosis, persistent unexplained elevations, or evidence of advanced fibrosis 3, 2

For harmful alcohol drinkers, perform risk stratification with FibroScan/ARFI elastography, and refer to hepatology if ARFI >7.8 kPa 2, 5
For children, maintain a low threshold for paediatric referral, and urgently assess neonatal cholestasis 3
For patients on immune checkpoint inhibitors, consider liver biopsy if steroid-refractory or if differential diagnoses would alter management 2