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Interpreting Abnormal LFT Patterns in Specific Diseases
The Two Core Patterns - Master This First
The most important first step in any abnormal LFT is determining whether the pattern is hepatocellular or cholestatic. This single distinction directs the entire workup.
| Feature | Hepatocellular | Cholestatic |
|---|
| Dominant rise | ALT, AST (>ALP) | ALP, GGT (>ALT, AST) |
| Key threshold | AST >3× URL, ALP <2× URL | AST <3× URL, ALP >2× URL |
| Bilirubin | Both conjugated + unconjugated raised | Mainly conjugated raised |
| Albumin/PT | Severely impaired in acute failure | May be normal initially |
| Think of | Hepatitis, drug toxicity, ischemia | Obstruction, PBC, PSC, drugs |
Disease-by-Disease LFT Interpretation
1. Acute Viral Hepatitis (A, B, C, D, E)
Hallmark: Dramatic ALT/AST elevation - typically >500 U/L, often >10-25× upper limit of normal (ULN)
| Test | Finding |
|---|
| ALT | Markedly elevated (≥ AST); rises days before jaundice |
| AST | Elevated, but ALT ≥ AST |
| ALP | Mildly elevated or normal |
| Bilirubin | Elevated (both fractions) once jaundice appears |
| Albumin | Normal (acute = no time to deplete) |
| PT/INR | Normal unless severe/fulminant |
Key rule: ALT ≥ AST in viral hepatitis. Values >25× ULN are almost exclusively seen in acute hepatocellular disease.
Caution on Hep C: ALT fluctuates in chronic HCV and can be normal even when AST is elevated - do not miss it.
2. Alcoholic Hepatitis
Hallmark: Moderate enzyme elevation with a distinctive AST:ALT ratio
| Test | Finding |
|---|
| AST | Elevated, but rarely >300 U/L |
| ALT | Lower than AST |
| AST:ALT ratio | ≥2:1 (De Ritis ratio reversal) - in severe cases up to 4:1 |
| GGT | Often markedly elevated (elevated in 70% of chronic alcoholics; correlates with alcohol intake) |
| Bilirubin | Elevated |
| PT | May be prolonged |
Mnemonic: "Two Shots to One" - AST is TWO times ALT in alcoholic hepatitis.
Why AST>ALT in alcohol? Alcohol depletes pyridoxal phosphate (vitamin B6) - ALT requires more B6 to be active than AST does. Also, alcohol directly damages mitochondria, releasing mitochondrial AST.
Distinguishing from viral hepatitis:
- Alcoholic: AST:ALT ≥2:1, AST rarely >300 U/L
- Viral: ALT ≥ AST, transaminases often >500-1000 U/L
3. Non-Alcoholic Fatty Liver Disease (NAFLD) / NASH
| Test | Finding |
|---|
| ALT | Mildly-moderately elevated (usually <5× ULN) |
| AST | May be normal or mildly elevated; ALT>AST initially |
| ALP/GGT | Mildly elevated |
| Albumin/PT | Normal unless cirrhosis has developed |
Key point: NAFLD is one of the most common causes of incidentally elevated liver enzymes in the Western world. Do NOT diagnose NAFLD on enzymes alone - suspect it when metabolic risk factors (obesity, T2DM, hypertension, dyslipidemia) are present.
When AST > ALT in NAFLD: Suggests progression to cirrhosis (ratio inverts as fibrosis develops).
4. Drug-Induced Liver Injury (DILI)
Two patterns exist:
| Type | LFT Pattern | Examples |
|---|
| Hepatocellular | ALT/AST >5× ULN dominant | Paracetamol, isoniazid, statins |
| Cholestatic | ALP >2× ULN dominant | Chlorpromazine, erythromycin estolate, anabolic steroids, OCP |
| Mixed | Both elevated | Many drugs |
- Predictable (dose-dependent): Classic example = paracetamol overdose. Causes extreme transaminase rise (>2000 U/L). Extreme elevation of LDH alongside extreme AST/ALT signals massive hepatic necrosis.
- Idiosyncratic: Not dose-dependent; minority of patients. Examples: isoniazid, halothane.
Hy's Law: If both ALT >3× ULN AND bilirubin >2× ULN in DILI - high risk of acute liver failure (mortality ~10%).
5. Cirrhosis (End-Stage Liver Disease)
Counterintuitive finding: Transaminases may be normal or only mildly elevated in cirrhosis because few functional hepatocytes remain to release enzymes.
| Test | Finding | Significance |
|---|
| ALT/AST | Normal or mildly elevated | Few hepatocytes left to lyse |
| AST:ALT ratio | >1 (reversal) | Fibrosis causes this flip |
| ALP/GGT | Elevated (biliary involvement) | |
| Albumin | Low | Best marker of chronicity/severity |
| PT/INR | Prolonged | Synthetic failure |
| Bilirubin | Elevated | Reflects severity |
| Platelets | Low (hypersplenism) | Portal hypertension |
| Ammonia | Elevated | Hepatic encephalopathy |
Mnemonic for cirrhosis: "LAPP" - Low albumin, AST>ALT, Prolonged PT, Platelets low
Child-Pugh Score uses LFTs to grade severity:
- Bilirubin, Albumin, PT, plus Ascites and Encephalopathy
- Score A (5-6) = compensated; Score C (10-15) = decompensated
6. Obstructive (Extrahepatic) Cholestasis
(e.g., gallstones, pancreatic cancer, bile duct stricture)
| Test | Finding |
|---|
| ALP | Markedly elevated (often >3-4× ULN) |
| GGT | Elevated in parallel with ALP |
| Conjugated bilirubin | Markedly elevated ("Can't get out") |
| ALT/AST | Mildly elevated or normal |
| Albumin | Normal early |
| PT | May be prolonged - corrects with vitamin K (malabsorption of fat-soluble vitamins) |
PT correction with Vitamin K = cholestasis, not hepatocellular failure. This is the key clinical differentiator.
Next step: Ultrasound - dilated bile ducts confirm extrahepatic obstruction; then CT/MRCP.
7. Intrahepatic Cholestasis
(e.g., Primary Biliary Cholangitis - PBC, Primary Sclerosing Cholangitis - PSC, drug-induced)
| Test | Finding |
|---|
| ALP | Markedly elevated |
| GGT | Elevated |
| Bilirubin | Elevated (conjugated) |
| ALT/AST | Mildly elevated |
| Anti-mitochondrial Ab (AMA) | Positive in PBC (>90% sensitivity) |
| IgM | Elevated in PBC |
| ANCA, ANA | May be positive in PSC/AIH |
- PBC: Middle-aged woman, itching, fatigue, elevated ALP + AMA positive.
- PSC: Young man with IBD, elevated ALP + beaded appearance on MRCP.
8. Ischemic Hepatitis ("Shock Liver")
Hallmark: Explosive transaminase rise
| Test | Finding |
|---|
| AST/ALT | Extreme elevation >2000-10,000 U/L (can mimic paracetamol overdose) |
| LDH | Also extremely elevated |
| Bilirubin | Rises later |
| PT | Prolonged |
Occurs with acute hypoperfusion (cardiogenic shock, septic shock, massive PE). Transaminases rise within 1-3 days then fall rapidly when perfusion is restored.
LDH + ALP both elevated = think malignant hepatic infiltration (metastases, lymphoma). LDH rises disproportionately.
9. Wilson Disease
| Test | Finding |
|---|
| AST:ALT | Elevated, often AST > ALT |
| ALP | Paradoxically LOW or normal (unique!) |
| Bilirubin | Elevated (Coombs-negative haemolytic anemia) |
| Ceruloplasmin | Low |
Low ALP in a young patient with hepatitis = think Wilson disease. This is a classic exam clue.
Summary Table: LFT Patterns at a Glance
| Disease | ALT/AST | ALP/GGT | Bili | Albumin | PT | Key Clue |
|---|
| Acute viral hepatitis | ↑↑↑ (ALT≥AST) | Normal/↑ | ↑ | Normal | Normal | ALT>500 U/L |
| Alcoholic hepatitis | ↑↑ (AST≥2×ALT) | ↑ GGT | ↑ | ↓ | ↑ | AST:ALT ≥2:1, AST<300 |
| NAFLD/NASH | ↑ (ALT>AST) | ↑ mild | Normal/↑ | Normal | Normal | Metabolic risk factors |
| Cirrhosis | Normal/↑ mild (AST>ALT) | ↑ | ↑ | ↓↓ | ↑↑ | Low albumin + reversed ratio |
| Extrahepatic obstruction | Normal/↑ mild | ↑↑↑ | ↑ conj | Normal | ↑ (corrects with vit K) | Dilated ducts on US |
| PBC/PSC | ↑ mild | ↑↑↑ | ↑ conj | ↓ late | ↑ late | AMA+ (PBC), IBD (PSC) |
| Ischemic hepatitis | ↑↑↑↑ | ↑ | ↑ | ↓ | ↑↑ | LDH also extreme; rapid fall |
| Wilson disease | ↑↑ (AST>ALT) | ↓ or normal | ↑ | ↓ | ↑ | Young patient, low ceruloplasmin |
| Liver metastases | ↑ mild | ↑↑↑ | ↑ | ↓ | ↑ | LDH + ALP both ↑↑ |
Quick Interpretation Algorithm
Abnormal LFTs
|
├── ALT/AST >> ALP? → HEPATOCELLULAR
│ |
│ ├── ALT ≥ AST + >500 U/L → Viral / toxic hepatitis
│ ├── AST:ALT ≥2:1, AST <300 → Alcoholic hepatitis
│ ├── AST:ALT >1, low albumin → Cirrhosis
│ ├── Extreme >2000 U/L → Ischemic or paracetamol
│ └── AST>ALT + LOW ALP → Wilson disease
│
└── ALP/GGT >> ALT/AST? → CHOLESTATIC
|
├── PT corrects with Vit K → Extrahepatic obstruction
│ └── US → dilated ducts → stone/stricture/tumour
└── Normal ducts on imaging → Intrahepatic cholestasis
├── AMA+ → PBC
├── IBD history → PSC
└── Drug history → Drug-induced cholestasis
Sources: Harrison's Principles of Internal Medicine, 22nd Ed.; Miller's Anesthesia, 10th Ed.; Quick Compendium of Clinical Pathology, 5th Ed.; Tietz Textbook of Laboratory Medicine, 7th Ed.