Initial Workup and Management of Elevated Liver Function Tests (LFTs)

Initial Assessment

The American Gastroenterological Association recommends obtaining a complete laboratory panel including ALT, AST, ALP, GGT, total and direct bilirubin, albumin, and prothrombin time/INR to determine the pattern and severity of liver injury 1
The initial workup should classify the pattern as hepatocellular (predominant ALT/AST elevation), cholestatic (predominant ALP/GGT elevation), or mixed 1
The severity of aminotransferase elevations should be categorized as mild (<5× ULN), moderate (5-10× ULN), severe (>10× ULN), or life-threatening (>20× ULN) 1
Reviewing medication history, including prescription drugs, over-the-counter medications, and supplements, is crucial in assessing the cause of elevated LFTs, as recommended by the British Society of Gastroenterology 2
Assessing alcohol consumption history using validated tools such as AUDIT-C is essential, as suggested by the British Society of Gastroenterology 3

Testing for viral hepatitis: anti-HAV IgM, HBsAg, anti-HBc IgM, and anti-HCV is recommended by the American Association for the Study of Liver Diseases 1
Screening for NAFLD risk factors: obesity, type 2 diabetes, dyslipidemia, and hypertension is suggested by the European Association for the Study of the Liver 2
For patients with NAFLD risk factors, performing risk stratification using FIB-4 or NAFLD Fibrosis Score is recommended by the European Association for the Study of the Liver 3
Considering autoimmune hepatitis: ANA, ASMA, ANCA if clinical suspicion is high is suggested by the American College of Gastroenterology 4

Confirming hepatic origin of elevated ALP by checking GGT is recommended by the British Society of Gastroenterology 2
Performing abdominal ultrasound to evaluate for biliary obstruction is suggested by the British Society of Gastroenterology 2
If ALP is elevated alone, checking GGT to confirm hepatic origin is recommended by the American College of Gastroenterology 4

Monitoring liver enzymes weekly until normalization is recommended by the American Gastroenterological Association 1
Discontinuing potentially hepatotoxic medications and alcohol is suggested by the American Society of Clinical Oncology 5

Monitoring liver enzymes every 2-3 days until stable or improving is recommended by the American Gastroenterological Association 1
For Grade 2 hepatic toxicity in patients on immune checkpoint inhibitors (AST/ALT >3.0 to ≤5.0× ULN), holding treatment temporarily and considering steroids (0.5-1 mg/kg/d prednisone) if no improvement after 3-5 days is suggested by the American Society of Clinical Oncology 4, 5

Monitoring liver enzymes every 1-2 days is recommended by the American Gastroenterological Association 1
For Grade 3 hepatic toxicity in patients on immune checkpoint inhibitors (AST/ALT 5-20× ULN), considering permanently discontinuing treatment and immediately starting steroids (1-2 mg/kg methylprednisolone) is suggested by the American Society of Clinical Oncology 5

Immediate hospitalization for intensive monitoring and supportive care is recommended by the American Gastroenterological Association 1
For Grade 4 hepatic toxicity in patients on immune checkpoint inhibitors, permanently discontinuing treatment is suggested by the American Society of Clinical Oncology 5

For harmful alcohol drinkers (>50 units/week for men, >35 units/week for women), performing risk stratification with Fibroscan/ARFI elastography is recommended by the British Society of Gastroenterology 3
Referring to alcohol services for adults with evidence of alcohol dependency (AUDIT score >19) is suggested by the British Society of Gastroenterology 3
For patients on immune checkpoint inhibitors with hepatitis, infliximab is contraindicated, as stated by the American Society of Clinical Oncology 5

Repeat testing frequency should be based on the severity of elevation and clinical context, as recommended by the American Gastroenterological Association 1
Considering liver biopsy if the patient is steroid-refractory or if there is concern for differential diagnoses that would alter management is suggested by the American College of Gastroenterology 4
Referring to hepatology for persistent unexplained elevations, evidence of advanced fibrosis, or ALT >5× ULN is recommended by the American Gastroenterological Association 1