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Clinical Approach to Abnormal Liver Enzyme Tests         Liver Cirrhosis Rx 2005                                                

Prevalence of abnormal liver enzyme tests during asymptomatic screening is not uncommon, estimated to be 1-4% by some author (Scand J Gastroenterol 1986;21:106 Hultcrantz R), and is up to one-third of patients screened by others (Mayo Clin Proc 1996; 71:1089 Patrick S. Kamath).


Physical Examination:

Clinical Assessment of the elevated ALT, AST Patients

  1. History & Physical Examination, & repeat to confirm elevation of liver enzyme tests
  2. If asymptomatic, & no elevated alk.phosphatase or bilirubin, may recheck in 3-6 months.
    If ALT >3-5x or duration > 6months, approach according to the disease suspected (risk factors)
  3. Consider liver biopsy if still abnormal.

Interpretation of abnormal aminotransferase/transaminase (ALT, AST) elevation:


Clinical Assessment of the elevated alkaline phosphatase & GGT Patients

  1. If alk.phos < 2X, < 6 months, & asymptomatic low risk patients, recheck test in 3-6 months.
    If disease is suspected, check ultrasound or CT scan of liver & biliary tract, then ERCP or liver biopsy as needed.
  2. If alk.phos > 2X, > 6 months, or symptomatic, check liver/bilirary tract ultrasound,
    if there is biliary dilatation, consider ERCP.
    if no biliary dilatation, consider antimitochondrial antibody & liver biopsy.
  3. If suspect alcohol or drug-related: recheck after 6-8 weeks of abstinence.
    If suspect viral hepatitis: viral serology markers.
    If suspect primary biliary cirrhosis: antimitochondrial antibody.
    If suspect primary sclerosing cholangitis: ERCP.
    Then liver biopsy if indicated.

Interpretation Abnormal Alkaline Phosphatase elevation:

Interpretation Abnormal Biblirubin elevation:


Hepatocellular diseases (increased ALT, AST)

Cholestatic diseases (elevated alk.phosphatase & GGT)

Medications with potential for hepatotoxicity

Nonalcoholic Steatohepatitis (fatty liver): perhaps the most common cause of mildly elevated liver enzymes in the US.  It is commonly seen in patients with obesity, diabetes, hyperlipidemia, medications, & jejunoileal bypass surgery.

Primary Biliary Cirrhosis: antimitochondrial antibody, elevated alk.phosphatase

Autoimmune liver disease: ANA >1:160 especially homogeneous pattern, smooth muscle antibody positivity.

Wilson's disease: low serum copper & cerulopasmin levels, low uric acid, Kayser-Fleischer rings.

Hemochromatosis: transferrin saturation >60% in men, >50% in women, & if the ferritin levels >1,000 ug/L.

Viral hepatitis: positivity of viral serologic markers as Hepatitis A-IgM, Hepatitis BsAg, Hepatitis BcAb (IgM), Hepatitis C Ab.

Extrahepatic cholestasis: diagnosed by liver sonography or CT scan, or ERCP.

Infiltrative liver disease: diagnosed by liver biopsy.

Cleveland Clin J Med 3/1998; 65:150 - Zobair Younossi
Mayo Clin Proc 11/1996;71:1089 - Patrick S. Kamath         


REF: DynaMed 2009  

Abnormal liver function tests - differential diagnosis

Updated 2009 Mar 20 02:05 PM: elevated serum alanine aminotransferase may be associated with liver disease mortality (Gastroenterology 2009 Feb)

AST and ALT actually reflect hepatocellular injury rather than liver function which is better reflected by albumin and prothrombin time

Elevated AST/ALT (Hepatocellular Injury)


Clinical significance:

Hepatic causes:


Alcohol use disorder (AST/ALT ratio = 2 with AST < 300 units/L and gamma-glutamyl-transpeptidase [GGT] 2 times normal levels)


viral hepatitis (aminotransferases peak before jaundice appears)

nonalcoholic fatty liver disease (steatosis/steatohepatitis)

less common

autoimmune hepatitis (liver enzymes mildly elevated)

hemochromatosis (check serum ferritin, iron and transferrin saturation)

alpha-1 antitrypsin (AAT) deficiency

Wilson's disease

hepatic metastatic disease

acute fatty liver of pregnancy

Reye's syndrome

Extrahepatic causes:

obesity - may have mildly elevated ALT and AST

unexplained aminotransferase elevation associated with higher body mass index in study of 15,676 adults in United States 1988-1994 (Am J Gastroenterol 2003 May;98(5):960)

celiac disease


Muscle injury - AST elevation

Strenuous exercise


idiopathic inflammatory myopathy


diabetes mellitus - 9.5% patients with type 1 diabetes and 12.1% patients with type 2 diabetes had elevated serum alanine aminotransaminase (ALT) levels in study of 1,353 patients with diabetes who did not have excessive alcohol consumption (QJM 2006 Dec;99(12):871)

Macro-AST (complex between normal AST and immunoglobulin)




amiodarone (Cordarone)



carbamazepine (Tegretol)


dantrolene sodium (Dantrium)

fluconazole (Diflucan)

flutamide (Eulexin)

glyburide (Micronase)


isoniazid (INH)

ketoconazole (Nizoral)

HMG-CoA reductase inhibitors (statins)

labetalol (Normodyne)



nitrofurantoin (Furadantin)

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, piroxicam

phenytoin (Dilantin)


protease inhibitors



trazodone (Desyrel)


Herbs and supplements:

Chaparral leaf (Larrea tridentata)



Germander (Teucrium chamaedrys)

Jin bu huan


Ma huang

Mistletoe (Viscum album)

Scutellaria (skullcap)

Senna (Cassia angustifolia)

Shark cartilage

Vitamin A


industrial solvents





beryllium - associated with granulomatous hepatitis

copper - associated with granulomatous hepatitis