Stethopedia | Approach

Approach to

Abnormal Liver Tests

Act first on liver failure, cholangitis, drug jaundice or acetaminophen. Then name the pattern: mild (<5× ULN) or marked (≥5×; >15× suggests acetaminophen or ischemia) hepatocellular, cholestatic, or isolated bilirubin.

  1. Abnormal ALT, AST, ALP or bilirubin on routine or acute testing
  2. Repeat tests; history: alcohol, drugs, supplements, metabolic and viral risk1,2
  3. R = (ALT/ULN) ÷ (ALP/ULN); bilirubin, INR, albumin, platelets1,12
  4. Liver failure, cholangitis or overdose?

Emergency: admit; hepatology, GI or toxicology

  • ALF: INR ≥1.5 + confusion, no cirrhosis3,12
  • Possible acetaminophen excess5
  • Fever, RUQ pain, jaundice11
  • Drug + ALT >3×, bilirubin >2× ULN (Hy's law)2
  • Shock, hypoglycemia, ↑lactate3
  • Pregnancy: HELLP, acute fatty liver12

→ NAC if acetaminophen risk or early ALF; ALF: ICU, transplant3,4,5

If not: which pattern?

CausesCluesWorkupManagement

Hepatocellular, mild

  • MASLD; alcohol-related disease
  • Drugs, herbal supplements2
  • HBV, HCV, iron overload, Wilson, autoimmune
  • Obesity, diabetes, dyslipidemia7
  • AST:ALT ≥2:1 suggests alcohol1,12
  • AST ≫ ALT, high CK: muscle, not liver12
  • HBsAg, anti-HBc, HCV Ab; iron studies1
  • ANA, anti-smooth muscle, IgG; ceruloplasmin1
  • Ultrasound; FIB-4 ≥1.3 → elastography7
  • Stop alcohol and culprit drugs2
  • MASLD: weight loss, treat metabolic risk7
  • HBV, HCV: refer for antivirals8,9

Hepatocellular, marked

  • Acetaminophen toxicity
  • Ischemia, HSV, Budd-Chiari, Wilson
  • Acute hepatitis A, B, E; drugs; autoimmune
  • Overdose, or repeated excess + alcohol5
  • ALT:LDH <1.5: ischemia, acetaminophen6
  • HSV: fever, anicteric; pregnant, immunosupp.3,12
  • Acetaminophen level even if no history5
  • HAV IgM, HBsAg, anti-HBc IgM, HSV PCR3
  • Doppler ultrasound; trend INR, glucose3
  • NAC now if acetaminophen possible5
  • Stop the drug; autoimmune: steroids2,12
  • Suspect HSV: empiric IV acyclovir3

Cholestatic or mixed

  • Cholangitis
  • Stone; pancreatic or biliary cancer
  • PBC, PSC, drugs, infiltration
  • Fever, RUQ pain, jaundice: Charcot11
  • Painless jaundice, weight loss: cancer
  • Itch, middle-aged woman: PBC; IBD: PSC1,10
  • High GGT confirms liver source of ALP1
  • Ultrasound: dilated ducts → MRCP/ERCP1
  • Normal ducts: AMA (PBC); MRCP (PSC)1,10
  • Cholangitis: antibiotics, then drainage11
  • Stones: ERCP, then cholecystectomy12
  • PBC: ursodiol 13–15 mg/kg/d10

Isolated bilirubin

  • Gilbert syndrome
  • Hemolysis; hematoma resorption
  • Direct: sepsis, TPN, drugs; Dubin-Johnson1
  • Indirect; rises with fasting, illness1
  • Anemia, high LDH, low haptoglobin
  • Fractionate: direct vs indirect1
  • CBC, smear, reticulocytes, haptoglobin
  • Direct: ultrasound, as for cholestasis1
  • Gilbert: reassure; no further tests1
  • Hemolysis: find and treat the cause

Can't-miss cause Superscripts link to the references below.

References

  1. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112:18–35. PubMed 27995906
  2. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116:878–898. PubMed 33929376
  3. Shingina A, Mukhtar N, Wakim-Fleming J, et al. Acute liver failure guidelines. Am J Gastroenterol. 2023;118:1128–1153. PubMed 37377263
  4. Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137:856–864. PubMed 19524577
  5. Dart RC, Mullins ME, Matoushek T, et al. Management of acetaminophen poisoning in the US and Canada: a consensus statement. JAMA Netw Open. 2023;6:e2327739. PubMed 37552484
  6. Cassidy WM, Reynolds TB. Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. J Clin Gastroenterol. 1994;19:118–121. PubMed 7963356
  7. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797–1835. PubMed 36727674
  8. Osiowy C, Alvarez F, Coffin CS, et al.; CASL Clinical Practice Guidelines Committee. The management of chronic hepatitis B: 2025 guidelines update from the Canadian Association for the Study of the Liver and AMMI Canada. Can Liver J. 2025;8:368–440. PubMed 40677987
  9. Bhattacharya D, Aronsohn A, Price J, Lo Re V; AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2023 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2023:ciad319. PubMed 37229695
  10. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69:394–419. PubMed 30070375
  11. Miura F, Okamoto K, Takada T, et al. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci. 2018;25:31–40. PubMed 28941329
  12. Gay E, Levy N, eds. Liver Chemistry Tests; Biliary Disease; Acute Liver Injury & Failure; Viral Hepatitis. In: Department of Medicine Housestaff Manual, 30th ed. 2024:84–87.

For education only; not a substitute for clinical judgment or local protocols. Where sources differ, the flowchart follows the current guideline.

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