How do you interpret Liver Function Tests (LFTs) in an adult patient with suspected liver disease?

Interpretation of Liver Function Tests in Adults with Suspected Liver Disease

Interpret LFTs by first identifying the pattern of injury (hepatocellular vs. cholestatic), then systematically investigating the underlying cause based on that pattern, while recognizing that normal LFTs do not exclude significant liver disease including cirrhosis. 1

Initial Laboratory Panel

Obtain a comprehensive panel including:

• Aminotransferases (ALT, AST) - markers of hepatocyte injury, with ALT being more liver-specific 1
• Alkaline phosphatase (ALP) - elevated in cholestatic disease 1
• Bilirubin (total and direct) - indicates hepatobiliary dysfunction 1
• Albumin - reflects synthetic function and suggests chronic disease when decreased 1
• Prothrombin time/INR - measures clotting factor synthesis, indicates impaired synthetic function 1
• Platelet count - thrombocytopenia suggests advanced disease 1

Pattern Recognition: The Critical First Step

Hepatocellular Pattern (Predominant Aminotransferase Elevation)

• ALT/AST ratio >2 suggests alcoholic liver disease, while ratio <1 suggests non-alcoholic fatty liver disease 1
• Classify severity: mild (<5× ULN), moderate (5-10× ULN), severe (>10× ULN), life-threatening (>20× ULN) 1, 2
• Initial serologic workup must include: hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibodies 1, 2
• For persistent elevations, add autoimmune markers (ANA, ASMA), iron studies, α1-antitrypsin, ceruloplasmin 1

Cholestatic Pattern (Predominant ALP Elevation)

• Confirm hepatobiliary origin with GGT or ALP fractionation - ALP can originate from bone, especially in post-menopausal women 3
• Evaluate for biliary obstruction with imaging (ultrasound, CT, or MRI) 1
• Consider drug-induced cholestasis, primary biliary cholangitis, or primary sclerosing cholangitis 3

Critical Pitfall: Normal LFTs Do Not Exclude Cirrhosis

Standard LFTs are only 38% sensitive for detecting hepatic fibrosis - patients can progress through significant fibrosis to cirrhosis with persistently normal liver enzymes 1. This is particularly true in:

• Non-alcoholic fatty liver disease 1
• Chronic hepatitis C 1
• Alcohol-related liver disease 1

When to Assess for Occult Fibrosis Despite Normal LFTs

In patients with risk factors (chronic alcohol use, viral hepatitis, metabolic syndrome), proceed with:

• Non-invasive fibrosis scores first: FIB-4 or NAFLD Fibrosis Score 1
• Elastography (FibroScan) if scores are indeterminate or elevated 1
• Screen for portal hypertension with platelet count and imaging 1
• Consider upper endoscopy to assess for varices if cirrhosis confirmed 1

Severity Assessment Beyond Single Parameters

Composite Scoring Systems

• Child-Pugh classification: incorporates albumin, bilirubin, INR, encephalopathy, and ascites 1
• MELD score: uses bilirubin, creatinine, and INR - originally for TIPS, now for transplant allocation 1
• ALBI grade: considers albumin and bilirubin for survival prediction 1

These composite scores are superior to any single parameter for assessing severity 4.

Critical Action Thresholds

When to Stop Hepatotoxic Medications

Discontinue immediately if: 2, 5

• ALT/AST >5× ULN
• Any elevation with jaundice or elevated bilirubin (regardless of absolute enzyme level)
• Bilirubin elevation in pre-existing liver disease

Monitoring Frequency Based on Severity

• Mild elevations (<5× ULN): weekly monitoring until normalization 5
• Moderate elevations (5-10× ULN): every 2-3 days until stable 5
• Severe elevations (>10× ULN): every 1-2 days, monitor ALT, AST, bilirubin, INR, albumin 2

Drug-Induced Liver Injury (DILI) Detection

Hepatocellular DILI Signals

Initiate accelerated monitoring when: 3

• ALT ≥5× ULN (if asymptomatic and bilirubin normal)

Interrupt study drug when: 3

• ALT ≥8× ULN with normal bilirubin
• ALT ≥3× ULN with total bilirubin ≥2× baseline
• ALT ≥5× ULN with liver-related symptoms (severe fatigue, nausea, worsening pruritus, right upper quadrant pain) or immunologic reaction (rash, >5% eosinophilia)

Cholestatic DILI Signals

Initiate accelerated monitoring when: 3

• ALP elevation 2× baseline without alternative explanation

Interrupt drug when: 3

• ALP >2× baseline combined with total bilirubin >2× baseline, or
• Doubling of direct bilirubin above baseline (if baseline >0.5 mg/dL), or
• New onset liver-related symptoms or immunologic features

Essential History Elements for Interpretation

Obtain targeted information on: 2

• All medications: prescription, over-the-counter, herbal supplements, illicit drugs, anabolic steroids
• Alcohol intake: use AUDIT-C scoring tool 2
• Viral hepatitis risk factors: injection drug use, high-risk sexual behavior, tattoos, country of birth, recent travel 2
• Metabolic risk factors: obesity, type 2 diabetes, dyslipidemia 3
• Family history: hemochromatosis, Wilson's disease 3

Common Pitfalls to Avoid

• Do not assume the magnitude of LFT elevation correlates with prognosis - context and diagnosis matter more than absolute values 3
• Do not routinely repeat LFTs hoping for normalization without investigating the cause - this delays diagnosis and is not cost-effective 5
• Do not exclude liver disease based on 2.5% false positive rate - 2.5% of healthy individuals will have abnormal elevation of a given test 1
• Do not continue hepatotoxic drugs with close monitoring when enzymes are >5× ULN - stop immediately and rechallenge only after normalization 5

Urgent Hepatology Referral Indications

Refer immediately for: 2

• Evidence of acute liver failure (rising bilirubin, prolonged INR, declining albumin, altered mental status)
• Severe liver enzyme elevation (>10× ULN)
• Suspected autoimmune hepatitis
• Any elevation with hepatic decompensation