ALT:AST Ratio
The ratio of ALT to AST provides important diagnostic clues about the etiology of liver disease:
Swipe to see more
| ALT:AST Ratio |
Interpretation |
Common Causes |
| >1 (ALT > AST) |
Typical for most liver diseases |
Viral hepatitis, NAFLD/NASH, drug-induced liver injury, autoimmune hepatitis |
| >2:1 (ALT >> AST) |
Highly suggestive of specific etiologies |
Acute viral hepatitis, NAFLD, drug-induced hepatitis |
| <1 (AST > ALT) |
Suggests alcoholic liver disease or cirrhosis |
Chronic alcohol use, advanced cirrhosis (any cause) |
| >2:1 (AST >> ALT) |
Classic for alcoholic hepatitis |
Alcoholic hepatitis, advanced cirrhosis, Wilson disease |
| >3:1 with AST <300 |
Strongly suggests alcohol |
Chronic alcoholic liver disease |
Pattern Recognition: Hepatocellular vs Cholestatic
The pattern of liver enzyme elevation helps distinguish hepatocellular injury from cholestatic or infiltrative processes:
Swipe to see more
| Pattern |
ALT/AST |
Alkaline Phosphatase |
R Value* |
| Hepatocellular |
Elevated (prominent) |
Normal or mildly elevated |
R ≥5 |
| Cholestatic |
Normal or mildly elevated |
Elevated (prominent) |
R ≤2 |
| Mixed |
Elevated |
Elevated |
R = 2-5 |
*R Value: (ALT ÷ ALT Upper Limit Normal) / (ALP ÷ ALP Upper Limit Normal). This ratio helps classify the pattern of liver injury.
Serial Measurements
Timing and Interpretation of Follow-up Testing
- Acute hepatitis: ALT peaks within 1-2 weeks, normalizes over 4-12 weeks in uncomplicated cases
- Acetaminophen toxicity: ALT peaks 24-72 hours post-ingestion, may reach >10,000 IU/L
- Ischemic hepatitis: Rapid rise and fall; ALT peaks 1-3 days after insult, then rapidly decreases
- Chronic liver disease: Persistently elevated for >6 months; fluctuations suggest ongoing injury
- Drug-induced liver injury: Variable pattern; should improve within weeks of stopping offending agent
- NAFLD/NASH: Persistently elevated, often fluctuating; may normalize with weight loss/lifestyle changes
When ALT Normalization is Concerning
Paradoxically, a falling or normalizing ALT can sometimes indicate worsening liver function:
- Acute liver failure: Falling ALT with rising INR/PT and bilirubin suggests massive hepatocyte loss
- End-stage cirrhosis: ALT normalizes as fewer hepatocytes remain to release enzyme
- Fulminant hepatitis: Rapid decrease in very high ALT with deteriorating synthetic function is ominous
Always interpret ALT in context with other liver function tests (albumin, INR, bilirubin) and clinical status.
Interfering Factors
Medications That Increase ALT
- Acetaminophen: Dose-dependent hepatotoxicity; therapeutic doses generally safe, but >4g/day or chronic use increases risk
- Statins: Mild elevation in 1-3% of patients; usually transient and clinically insignificant
- Antibiotics: Amoxicillin-clavulanate, nitrofurantoin, sulfonamides, isoniazid, rifampin
- Anticonvulsants: Phenytoin, valproic acid, carbamazepine
- NSAIDs: Particularly diclofenac; risk increases with chronic use
- Antifungals: Ketoconazole, fluconazole, itraconazole (especially with prolonged therapy)
- Antiretrovirals: Many HIV medications can cause hepatotoxicity
- Herbals/supplements: Kava, green tea extract, anabolic steroids, many others
- Immunosuppressants: Methotrexate, azathioprine
- Cardiovascular drugs: Amiodarone, hydralazine
Pre-analytical Factors Affecting Results
- Hemolysis: Can falsely elevate ALT due to release from red blood cells (though effect is less than with AST)
- Strenuous exercise: Vigorous activity within 24 hours can mildly elevate ALT from muscle injury
- Specimen storage: ALT is relatively stable at room temperature for 24 hours; refrigeration preferred for longer storage
- Lipemia: Severe hypertriglyceridemia may interfere with some assay methods
Physiologic Factors
- Body mass index (BMI): Obesity increases ALT due to NAFLD prevalence
- Gender: Males have 10-30% higher baseline ALT than females
- Age: Slight increase with age, though elderly may have lower values
- Ethnicity: Some variation exists across different ethnic groups
- Muscle mass: Higher muscle mass associated with slightly higher ALT
- Pregnancy: Normally unchanged; elevation suggests pregnancy-specific liver disease (HELLP, acute fatty liver)
Conditions Causing Falsely Normal or Low ALT
- Vitamin B6 (pyridoxine) deficiency: Required as cofactor for ALT; severe deficiency lowers measured ALT
- Chronic kidney disease: May have lower ALT levels
- Advanced cirrhosis: Normalized ALT despite ongoing liver dysfunction due to reduced hepatocyte mass
Extrahepatic Sources of ALT
While ALT is considered liver-specific, it is also present in smaller amounts in:
- Skeletal muscle: Severe rhabdomyolysis can mildly elevate ALT (though CK elevation is much more prominent)
- Kidney: Renal disease rarely causes isolated ALT elevation
- Heart: Myocardial infarction typically causes minimal ALT elevation compared to AST
Clinical Pearl: If extrahepatic sources are suspected, check CK (for muscle), troponin (for heart), and consider imaging or additional testing. True isolated ALT elevation is almost always hepatic in origin.
Clinical Pearls
- "ALT is the Alanine Liver Test": ALT is more specific for liver injury than AST, which is also elevated in cardiac and muscle disease. When both are elevated, consider the source; when only ALT is elevated, think liver first.
- The "2:1 Rule" for alcohol: In alcoholic hepatitis, AST is typically more than twice ALT, and both are usually <300 IU/L. If you see AST:ALT ratio >2:1 with both values <300, alcohol should be your top differential. Remember: "AST is Above with Sauce (alcohol)."
- Don't miss acetaminophen toxicity: Any patient with massive transaminitis (ALT >1000 IU/L) needs an acetaminophen level checked immediately, even with no reported ingestion. Many cases are unintentional overdoses from combination products or therapeutic misadventure.
- "Normal ALT doesn't mean normal liver": Patients with cirrhosis often have normal or near-normal transaminases because there are few hepatocytes left to die. Always assess synthetic function (albumin, INR) and imaging to evaluate for chronic liver disease, not just ALT.
- The magnitude matters more than you think: ALT >1000 IU/L has a very limited differential: acute viral hepatitis, ischemic hepatitis, acetaminophen toxicity, autoimmune hepatitis, Budd-Chiari, or toxins. Chronic liver diseases (NAFLD, chronic hepatitis) rarely cause such dramatic elevations.
- Beware the falling ALT with rising bilirubin: In acute liver failure, a rapidly declining ALT combined with worsening coagulopathy (rising INR) and rising bilirubin is a sign of massive hepatocyte necrosis and impending liver failure—not improvement.
- NAFLD is now the most common cause: In Western countries, non-alcoholic fatty liver disease is the leading cause of chronic ALT elevation. Screen patients with metabolic syndrome, obesity, or diabetes for NAFLD if ALT is persistently elevated.
- Ischemic hepatitis is "the forgotten cause": In ICU or ED patients with massive transaminitis (often >1000 IU/L) and recent hypotension, cardiac arrest, or shock, consider ischemic hepatitis ("shock liver"). LDH is also markedly elevated. ALT rises rapidly and falls rapidly once perfusion is restored.
- When to repeat testing: Isolated mild ALT elevation (1-2x ULN) should be repeated in 2-4 weeks to confirm it's not transient. Persistently elevated ALT (>6 months) requires further workup. Acute severe elevation requires immediate investigation.
- Check for hemolysis before panicking: If ALT seems disproportionately high or the specimen looks pink/red, hemolyzed samples can cause falsely elevated results. Request a repeat non-hemolyzed sample before extensive workup.
- Compare to ALP to determine the pattern: Calculate the R value: (ALT/ALT_ULN) / (ALP/ALP_ULN). R ≥5 = hepatocellular, R ≤2 = cholestatic, R 2-5 = mixed. This pattern directs your diagnostic approach and imaging choices.
- Don't forget non-hepatic causes in the right context: Celiac disease, thyroid disease, and muscle disorders can all cause mild ALT elevation. If liver workup is negative and ALT is <100, consider these diagnoses.
- "Statins rarely require discontinuation": Mild ALT elevation (<3x ULN) with statins is common and usually benign. Current guidelines recommend continuing statins and monitoring unless ALT >3x ULN persists. The cardiovascular benefit usually outweighs mild transaminitis.
- Viral hepatitis time course: In acute viral hepatitis A or B, ALT typically peaks at 1-2 weeks and normalizes by 3-4 months. Persistently elevated ALT beyond 6 months suggests chronic hepatitis (only possible with HBV and HCV, not HAV).
- Think zebras when nothing else fits: If workup for common causes is negative and ALT remains elevated, consider Wilson disease (especially age <40), alpha-1 antitrypsin deficiency, hemochromatosis, or autoimmune hepatitis. These are rare but treatable.
References
- Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
- Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
- Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape. https://emedicine.medscape.com/article/2172316-overview?form=fpf
- Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL. https://litfl.com/ccc-critical-care-compendium/
- Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/toc/