Elevated transaminases

Last updated: January 9, 2025

Summary

Elevated transaminases are typically a sign of hepatocellular injury and most commonly caused by alcohol-associated liver disease or metabolic dysfunction associated steatotic liver disease (MASLD). The initial diagnostic workup comprises liver chemistries that include both alanine transaminase (ALT) and aspartate transaminase (AST), and an RUQ ultrasound. If signs of acute liver failure are present (e.g., altered mental status, jaundice), initiate urgent management and consult hepatology. A referral for liver biopsy may be considered for patients in whom the etiology remains unclear.

Definitions

Elevated transaminases: elevation of ALT and/or AST above the upper limit of normal (ULN) ^[1]
- Massively elevated transaminases: ALT and/or AST > 10,000 U/L
- Severely elevated transaminases: ALT and/or AST > 15× ULN
- Moderately elevated transaminases: ALT and/or AST 5–15× ULN
- Mildly elevated transaminases: ALT and/or AST 2–5× ULN
- Borderline elevated transaminases: ALT and/or AST < 2× ULN
Hepatocellular injury pattern: disproportionate elevation of AST and ALT compared to alkaline phosphatase (ALP) ^[1]
Mixed injury pattern: proportionally elevated ALP and transaminases ^[1]
Cholestatic injury pattern: disproportionate elevation of ALP compared to AST and ALT (see “Jaundice and cholestasis”) ^[1]

Etiology

The causes of cholestatic liver injury are covered in “Jaundice and cholestasis.”

Causes of elevated transaminases and typical AST/ALT ratio ^[1]
	AST > ALT	ALT > AST
Severe elevation of transaminases	Ischemic hepatitis Rhabdomyolysis Acute liver failure of any etiology Vascular disorders, e.g.: Acute hepatic vein thrombosis Hepatic artery occlusion Acute Budd-Chiari syndrome Congestive hepatopathy ^[2]	Toxic ingestion, e.g., mushroom poisoning, drug-induced liver injury Viral infections Acute viral hepatitis Acute EBV, CMV, or HSV Acute bile duct obstruction Autoimmune hepatitis Liver trauma (e.g., after surgery) Liver metastases Sinusoidal obstruction syndrome HELLP syndrome Septic shock Wilson disease
Nonsevere elevation of transaminases	Alcohol-associated hepatitis Cirrhosis of any etiology Muscle damage, e.g., myocardial infarction, strenuous exercise Total parenteral nutrition Macro-aspartate transaminasemia ^[3]	Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease (MASLD) Chronic viral hepatitis Hemochromatosis Alpha-1-antitrypsin deficiency (AATD) Celiac disease Acute fatty liver of pregnancy Hemophagocytic lymphohistiocytosis
Nonsevere elevation of transaminases	Thyroid disease

The ratio of AST serum levels to ALT serum levels can be used to narrow down the etiology of hepatocellular injury.

Clinical evaluation

Focused history ^[1]

Patient history
- Nonspecific clinical features, e.g., fatigue, nausea, unintentional weight loss.
- Exposures
  - Alcohol
  - Hepatotoxic medications, e.g., acetaminophen, isoniazid, phenytoin
  - Foraged mushrooms, e.g., Amanita phalloides
  - Herbal supplements, e.g., Ephedra sinica ^[4]
  - Viral hepatitis
- Cardiometabolic risk factors for MASLD
Family history: AIH, hemochromatosis, Wilson disease, AATD

Patients with nonsevere elevation of transaminases are often asymptomatic and have normal physical examination findings.

Focused examination ^[1]

Assess for any of the following:

Signs of acute liver failure
Signs of chronic liver disease
Features of metabolic syndrome, e.g., abdominal obesity, hypertension
Signs of specific conditions, e.g., Kayser-Fleischer rings

Diagnosis

The following focuses on diagnostics for patients with a hepatocellular injury pattern. See “Diagnostics for cholestasis” in patients with a mixed or cholestatic injury pattern.

Approach ^[1]

Perform a focused clinical evaluation.
Consider causes based on patient history, e.g., alcohol-associated fatty liver, MASLD, or drug-induced liver injury.
Order routine laboratory studies for all patients, including repeat transaminases.
Obtain imaging and additional laboratory studies depending on severity.
- Borderline or mild elevation: Consider 3–6 months of observation before repeat testing of AST, ALT, and ALP; obtain additional testing if elevation persists or worsens. ^[1]
- All other patients: Obtain simultaneously with routine laboratory studies.
Consider referral for liver biopsy if the etiology remains unknown.

In patients with elevated transaminases, advise discontinuation of any hepatotoxic medications and avoidance of alcohol.

Routine laboratory studies ^[1]

Liver chemistries
- Transaminases ^[1]
  - To confirm true elevation and determine severity
  - Normal values: ALT ≤ 33 IU/L (♂) or ≤ 25 IU/L (♀), AST ≤ 18 IU/L
- ALP and total bilirubin: to establish injury pattern
- Albumin: to assess hepatic synthetic function
CBC: to assess for thrombocytopenia
Coagulation studies: to assess hepatic synthetic function

For patients with transaminases < 5× ULN (i.e., borderline or mild), consider 3–6 months of observation if initial routine studies do not reveal a diagnosis. ^[1]

Additional studies ^[1]

Severe elevation of transaminases

Laboratory studies
- Hepatitis C serology, hepatitis B serology, anti-HAV IgM
- Hepatitis E serology if positive travel history to endemic areas
- PCR for nonhepatotropic viruses: HSV, EBV, CMV
- Ceruloplasmin to screen for Wilson disease in patients < 55 years of age
- Autoimmune hepatitis serology, e.g., ANA, ASMA, SPEP, Anti LKM1
- Serum and urine toxicology testing to assess for drug-induced liver injury
Doppler RUQ ultrasound

For patients with severely elevated transaminases, order initial and additional laboratory studies concomitantly, along with an RUQ ultrasound.

Nonsevere elevation of transaminases

All patients
- Laboratory studies
  - Iron studies to screen for iron overload disorders
  - Hepatitis C serology, hepatitis B serology
  - Ceruloplasmin to screen for Wilson disease in patients < 55 years of age
  - Autoimmune hepatitis serology, e.g., ANA, ASMA, SPEP
  - α1-antitrypsin (AAT) levels for AATD
- RUQ ultrasound
Moderately elevated transaminases: Also test for hepatitis A (anti-HAV IgM, anti-HAV IgG) in patients with acute hepatitis and possible exposure.
Borderline or mildly elevated transaminases: Consider further testing based on clinical suspicion, e.g., for tick-borne diseases, celiac disease, hypothyroidism, and/or metabolic syndrome. ^[5]

Diagnostic approach to elevated transaminases

Management

Discontinue alcohol and hepatotoxic medications.
Provide management of acute liver failure as indicated, e.g.:
- Emergency stabilization
- Consult with hepatology urgently.
- Request transfer of care to a liver transplant center.
Base additional management on the underlying cause.

Common causes of nonsevere elevation of transaminases

Common causes of nonsevere elevation of transaminases ^[1]
Conditions	Distinguishing clinical features	Diagnostic findings	Management
Alcohol-associated liver disease	History of significant alcohol consumption	AST/ALT > 1.5 ↑ GGT ↑ Serum ferritin Macrocytic anemia INR > 1.5 in alcohol-associated hepatitis	Cessation of alcohol use See “Treatment of alcohol-associated hepatitis.”
MASLD	Risk factors for MASLD Absence of other known causes of steatotic liver disease (e.g., heavy alcohol use)	AST/ALT < 1	Treatment of obesity and metabolic syndrome See “Management of MASLD.”
Cirrhosis	Signs of cirrhosis, e.g., jaundice, scleral icterus	Thrombocytopenia ↑ PT, ↑ INR ↓ Albumin, ↑ bilirubin, ↓ platelets Ultrasound: nodular liver surface	See “Treatment of cirrhosis.”
Hemochromatosis	Symptoms of organ iron accumulation, e.g., hepatomegaly, diabetes mellitus, bronze skin, arthralgia, cardiomyopathy	↑ Serum ferritin and iron, ↑ transferrin saturation	Therapeutic phlebotomy See “Treatment of hemochromatosis.”
Alpha₁ antitrypsin deficiency (AATD)	Pulmonary and/or hepatic symptoms with variable onset	Serum AAT < 1.1 g/L ^[6] Panlobular emphysema	Avoidance of triggers, e.g., cigarette smoke Symptomatic treatment Antitrypsin replacement
Celiac disease	Chronic diarrhea, weight loss Dermatitis herpetiformis	↑ IgA tissue transglutaminase antibody See also “Diagnostics for celiac disease.”	Gluten-free diet
Acute fatty liver of pregnancy (AFLP) ^[7]	Typically third trimester of pregnancy Sudden onset of jaundice Nausea, vomiting, RUQ pain Encephalopathy Polyuria and polydipsia	Hypoglycemia, normal GGT, ↓ platelets, ↓ coagulation factors, ↑ WBC Ultrasound: hyperechoic, bright white liver; ascites may be present	AFLP is an obstetrical emergency; consult OB/GYN and critical care teams urgently.
Budd-Chiari syndrome ^[8]	Signs of portal hypertension Tender hepatomegaly	Hepatic vein occlusion on Doppler ultrasound or CT abdomen	Treat underlying cause. Anticoagulation Thrombolysis or stenting to restore blood flow

Common causes of severe elevation of transaminases

Common causes of severe elevation of transaminases ^[1]
Conditions	Distinguishing clinical features	Diagnostic findings	Management
Ischemic hepatitis	Acute decrease of blood flow to the liver, e.g., due to cardiogenic shock	Typically massively elevated transaminases AST > ALT Evidence of other end-organ damage (e.g., ↑ creatinine)	Treat the underlying condition. Hemodynamic support Supportive care
DILI	History of exposure to medication or toxin	May have massively elevated transaminases ALT > AST Mixed, hepatocellular, or cholestatic injury pattern	Discontinue causative drug and/or toxin. Supportive care See “Treatment of DILI.”
Rhabdomyolysis	History of crush injury or prolonged immobilization Clinical features of rhabdomyolysis (e.g., myalgias, weaknesses, dark urine)	May have massively elevated transaminases ↑ CPK (> 5× ULN or > 1000 IU/L)	IV fluid resuscitation See “Management of rhabdomyolysis.”
Acute viral hepatitis	Fever, malaise, vomiting Individual risk factors: Risk factors for HBV infection Risk factors for HCV infection Risk factors for HAV infection	ALT > AST	See “Treatment of hepatitis B infection.” See “Treatment of hepatitis C infection.” See “Treatment of hepatitis A infection.”
Congestive hepatopathy	Clinical features of right heart failure	AST > ALT initially ↑ Serum bilirubin ↑ BNP	Treat underlying cause. See “Treatment of heart failure.”
Acute biliary obstruction	Biliary colic	Abdominal imaging: gallstones, malignancy, or cysts	Treatment of the underlying cause, e.g., cholecystectomy, biliary stenting
Autoimmune hepatitis (AIH)	Possibly other autoimmune conditions (e.g., Hashimoto thyroiditis, celiac disease)	Positive antibodies (e.g., ANA and ASMA for type 1 AIH, anti-LKM-1 for type 2 AIH)	Glucocorticoids See “Treatment of autoimmune hepatitis.”
Septic shock	Clinical features of sepsis Hypotension	↑ Lactate	Management of sepsis, e.g.: IV fluid resuscitation Antibiotics Vasopressors
HELLP	Preeclampsia	Hemolysis, low platelets See “Diagnostics” in “Hypertensive pregnancy disorders.”	See “Management of HELLP.”
Hepatic artery thrombosis	Recent liver transplantation or other surgical procedure (e.g., pancreaticoduodenectomy) ^[9]	Diagnosed via Doppler ultrasound or CT abdomen	Thrombectomy or thrombolysis Stenting Retransplantation (in the setting of post-liver transplant complication)
Wilson disease	Kayser-Fleischer rings Cerebellar symptoms (e.g., dysarthria, gait abnormalities) Psychosis	↓ Serum ceruloplasmin ↑ 24-hour urine copper	Chelating agents See “Treatment of Wilson disease.”

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