Updated October 2025

Hepatology | Practical Pathway

Approach to Abnormal Liver Function Tests (LFTs)

A pattern-based, stepwise evaluation of abnormal liver blood tests emphasizing urgency triage, common etiologies, targeted diagnostics, and initial management. Focus on distinguishing hepatocellular vs cholestatic injury, ruling out life-threatening causes, and avoiding indiscriminate testing while ensuring timely follow-up.

Clinical question

What is an evidence-based, clinically efficient approach to evaluating and managing abnormal liver function tests in adults?

HepatologyPrimary CareEmergency MedicineDiagnosticsNAFLDDrug-induced liver injury

Key points

Identify emergencies first

Red flags (jaundice, coagulopathy, encephalopathy, sepsis, severe RUQ pain) mandate urgent evaluation for acute liver failure, biliary obstruction, or cholangitis ^[7], ^[1].

Classify the pattern

Calculate R ratio: (ALT/ULN) ÷ (ALP/ULN). R ≥5 hepatocellular; R ≤2 cholestatic; 2<R<5 mixed. Pattern directs labs and imaging ^[5], ^[8].

Repeat and confirm

Verify abnormal results, review prior values, and repeat in 2–4 weeks when clinically stable to avoid over-testing and false positives ^[6], ^[11].

Targeted first-line tests

History-driven labs (viral hepatitis, alcohol, metabolic, autoimmune) and ultrasound for cholestasis or steatosis streamline work-up ^[7], ^[8], ^[6].

Treat reversible causes

Alcohol abstinence, stop culprit drugs/supplements, vaccinate (HAV/HBV), manage NAFLD with weight loss and metabolic control; escalate when high-risk features present ^[10], ^[7], ^[1].

Evidence highlights

NAFLD, alcohol, medications/supplements ^[10], ^[7]

Most common outpatient causes

Hepatocellular vs cholestatic guides testing ^[5], ^[7], ^[8]

Pattern recognition

Focused, tiered over indiscriminate panels ^[6], ^[11]

Testing strategy

Foundation

Stepwise Approach

A concise pathway from triage to targeted diagnostics and initial management.

1) Triage for severity and stability

Assess for encephalopathy, INR ≥1.5, bilirubin ≥3 mg/dL, rapidly rising aminotransferases, hypotension, or sepsis. Presence of jaundice + systemic toxicity raises concern for acute liver failure or ascending cholangitis; initiate emergent evaluation, resuscitation, and specialty consultation ^[7], ^[1].

2) Confirm abnormality and define pattern

Repeat AST, ALT, ALP, GGT, bilirubin (total/direct), albumin, INR; review prior results. Determine R ratio to classify hepatocellular, cholestatic, or mixed injury. Pattern recognition is central to narrowing differential and ordering the right tests ^[5], ^[8].

3) Focused history and exam

Alcohol use (quantity, pattern), medications and herbals/supplements, viral risks (travel, exposures), metabolic syndrome, autoimmune history, pruritus, RUQ pain, heart failure symptoms. Incidental mild elevations are common; context determines urgency and depth of work-up ^[10], ^[7].

4) Initial targeted tests

Hepatocellular pattern: HAV IgM (if acute), HBsAg, anti-HBc IgM/total, HCV Ab with reflex RNA, acetaminophen level, pregnancy test (when relevant), CK (muscle source), ferritin and transferrin saturation, autoimmune panel (ANA, ASMA, IgG) when persistent. Cholestatic pattern: fractionated bilirubin, GGT, right-upper-quadrant ultrasound for ductal dilation; if dilated or cholangitis suspected, urgent ERCP consideration. Mixed pattern: combine approaches ^[7], ^[8], ^[6].

5) Imaging strategy

Ultrasound is first-line for suspected biliary disease or steatosis. No ductal dilation but persistent cholestasis: consider MRCP for intrahepatic cholestasis or PSC; CT if mass suspected. Use ultrasound in ED to rapidly identify obstruction or steatosis when labs are abnormal ^[9], ^[7].

6) Management of common etiologies

Alcohol-related: strict abstinence, withdrawal management, nutrition; consider corticosteroids only for severe alcoholic hepatitis (specialist-guided) ^[1]. NAFLD: ≥7–10% weight loss target, optimize diabetes, lipids, blood pressure; screen for advanced fibrosis (FIB-4, elastography) ^[10]. DILI: stop the offending agent; report severe cases; consider N-acetylcysteine for suspected acetaminophen toxicity. Viral hepatitis: treat per guidelines; counsel transmission prevention ^[7], ^[8].

7) When to refer or escalate

Immediate referral: acute liver failure, cholangitis/obstruction, bilirubin >3 mg/dL with coagulopathy, AST/ALT >1000 U/L, suspected autoimmune hepatitis with jaundice, or uncertain diagnosis with worsening labs. Refer for elastography or hepatology when persistent elevation >6 months, FIB-4 ≥1.3 (≥2.0 if age >65), platelets low, or imaging suggests advanced fibrosis ^[7], ^[6], ^[8].

Bedside

Pattern-Based Differential and First Tests

Use pattern recognition to guide targeted, high-yield diagnostics and avoid unnecessary testing.

Hepatocellular (R ≥5)

Common: NAFLD, alcohol, viral hepatitis, DILI, ischemic hepatitis, autoimmune hepatitis ^[7], ^[8], ^[10]

Key tests: HBV (HBsAg, anti-HBc), HCV Ab→RNA, HAV IgM (if acute), acetaminophen level, CK, ferritin/TSat, ANA/ASMA/IgG ^[7], ^[8]

Consider: Wilson disease (younger patients), hemochromatosis (TSat ≥45%), thyroid disease, celiac if persistent

Imaging: Ultrasound for steatosis, vascular flow if ischemic suspected

Cholestatic (R ≤2)

Common: Gallstones, malignancy, PSC, PBC, DILI (e.g., cholestatic), sepsis-associated cholestasis ^[7], ^[8]

Key tests: Fractionated bilirubin, GGT, antimitochondrial antibody (AMA), ultrasound for ductal dilation; MRCP if nondiagnostic ^[7]

Urgent: Cholangitis signs → antibiotics + biliary decompression (ERCP) ^[7]

Consider IgG4 if pancreatobiliary involvement suspected

Mixed (2<R<5)

Consider: DILI, alcoholic hepatitis, obstructive processes with secondary hepatocellular injury, infiltrative disease ^[8]

Approach: Combine hepatocellular and cholestatic testing; image early with ultrasound ± MRCP

When to repeat vs. pursue immediately

Mild asymptomatic elevation (<2× ULN) without red flags → repeat in 2–4 weeks while removing potential offenders ^[6], ^[11]

≥3× ULN, symptoms, jaundice, or coagulopathy → full work-up now ^[7]

Transient rises common with intercurrent illness, strenuous exercise, or muscle injury (check CK) ^[8]

Initial Management Pearls

Stop hepatotoxic agents/supplements; review OTCs and herbals ^[7], ^[8]

Alcohol abstinence and withdrawal prevention; provide nutrition in suspected alcoholic hepatitis ^[1]

Vaccinate against HAV/HBV if non-immune and at risk ^[7]

NAFLD: diet, exercise, weight loss, treat metabolic syndrome; consider noninvasive fibrosis staging ^[10]

Avoid over-testing

Use a tiered, risk-driven algorithm rather than exhaustive panels initially ^[6], ^[11]

Escalate to second-line tests (A1AT phenotype, ceruloplasmin, IgG4, celiac serologies) only when indicated by pattern or persistence ^[7], ^[8]

Operations

ED-Focused Considerations

Stabilize, rule out time-sensitive disease, and defer nonurgent etiologies.

Immediate actions

Assess airway, mental status, glucose; check INR, bilirubin, ammonia (context), lactate

Broad-spectrum antibiotics if cholangitis suspected; obtain blood cultures ^[1], ^[7]

Bedside RUQ ultrasound for obstruction/stone; early GI for ERCP if indicated ^[9]

Consider N-acetylcysteine for acetaminophen toxicity or indeterminate acute liver failure ^[7]

ED disposition

Admit: ALF, cholangitis, biliary obstruction with cholestasis, severe alcoholic hepatitis, AST/ALT >1000 with systemic illness ^[1], ^[7]

Outpatient follow-up: Mild asymptomatic elevations; provide explicit follow-up in 2–4 weeks ^[6], ^[11]

Quality

Documentation and Follow-up

Close-loop follow-up prevents missed progressive liver disease.

Clear plan

Document suspected etiology, tests ordered, and repeat timeline. Educate on alcohol abstinence, acetaminophen limits, and avoidance of new supplements.

Risk stratify fibrosis

Calculate FIB-4 using age, AST, ALT, platelets; FIB-4 ≥1.3 (≥2.0 if >65) warrants elastography or hepatology referral in NAFLD or unexplained elevations ^[10], ^[6].

Reassess persistently abnormal LFTs

If abnormal >6 months or worsening, broaden evaluation (autoimmune, metabolic, infiltrative) and consider liver biopsy after noninvasive work-up ^[7], ^[8].

References

Source material

Primary literature that informs this article.