Overview
Background Transaminases Alkaline phosphatase Bilirubin Other liver labs Summary
Background
Liver function tests ordered routinely 1-4% of asymptomatic patients have abnormal values Components
Transaminases Alkaline phosphatase Bilirubin Others: albumin, protein
Transaminases
Located in hepatocytes
Released after hepatocellular injury
2 Forms
AST Non-specific to liver: heart, skeletal muscle, blood ALT More specific: elevated in myopathies
Transaminases
May not be elevated in chronic liver disease
HCV- apoptosis Cirrhosis
Transaminases
Mild elevations more to come Marked elevations
Acute toxic injury- ie tylenol, ischemia Acute viral disease Alcoholic hepatitis
Transaminases
AST:ALT ratio
Elevated in alcoholic disease
2:1 If AST > 500 consider other cause
Mild Transaminitis
AST/ALT < 5 times upper limit of normal Etiologies
Hepatic: ALT-predominant Chronic Hep C Hemochromatosis Chronic Hep B Medications/Toxins Acute viral hep Autoimmune Hep Steatosis Alpha1 Antitrypsin Def Wilsons Disease Celiac Disease
Mild Transaminitis
Hepatic: AST predominant
Alcohol Steatosis Cirrhosis
Non-hepatic
Hemolysis Myopathy Thyroid disease Strenuous exercise
Elevated AST & ALT, <5X normal Hx & physical; stop hepatotoxic meds
Negative serology
Positive serology
Hepatotoxic Medications
Analgesics- acetaminophen, NSAIDS Antimicrobials
Amox-clav, nitrofurantoin, sulfonamides INH Azoles Protease Inhibitors
Hepatotoxic Medications
Cardiovascular- alpha-methyldopa,
amiodarone, labetalol Hyperglycemics- glyburide, troglidazone
Hepatotoxic Herbals
Chaparral leaf Ephedra Gentian Germander Jin Bu Huan Senna, Kavakava Scutellaria (skullcap) Shark cartilage Vitamin A
Repeat LFTs
Abnormal Normal
Ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin, gliadin & endomysial Ab Liver biopsy
Observation
Liver biopsy
Positive Serologies
Hep A IgM + Hep C/B infection Follow clinically, serial LFTs Persistent elevated LFTs > 6 mos
Observation
Observation
Liver biopsy
HCV
HCV Ab- during or after infection HCV-RNA- during infection Detectable prior to HCV Ab turning positive
Total anti-HBc
Titre
HBsAg IgM anti-HBc anti-HBs
12 16 20 24 28 32 36
52
100
Alkaline Phosphatase
Produced by biliary epithelial cells Non-specific to liver: bone, intestine, placenta Elevations Biliary duct obstruction Primary biliary cirrhosis Primary sclerosing cholangitis Infiltrative liver disease- ie sarcoid, lymphoma Hepatitis/cirrhosis Medications
Medications
Hormones- anabolic steroids, estrogen,
methyltestosterone
Cardiovascular- captopril, diltiazem, quinidine Hyperglycemics- chlorpropamide, tolbutamide Psychiatric- fluphenazine, imipramine, iprindole Others- allopurinol, carbamazepine
GGT or 5-NNT
Other source
No dilatation
+
RUQ us, med review, AMA
Yes
No
ERCP
AMA
Neg
Observation Liver bx
AP > 6 mo
Bilirubin
Product of hemoglobin breakdown 2 Forms
Unconjugated (indirect)- insoluble in hemolysis, Gilbert syndrome, meds Conjugated (direct)- soluble in obstruction, cholestasis, cirrhosis, hepatitis, primary biliary cirrhosis, etc. No elevation until loss of > 50% capacity
Elevated Bilirubin
Unconjugated bili; Normal alk phos, ALT, AST Conjugated bili; Abnormal alk phos, ALT, AST
+
ERCP or MRCP
Summary
Algorithms based on poor quality or absence of evidence Most asymptomatic patients can safely be followed for a period of time to see if abnormalities resolve If lab abnormalities persist be thoughtful with ordering
References
AGA Clinical Practice Committee. AGA medical position statement: evaluation of liver chemistry tests. Gastroenterology 2002;123:1364-66. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 2002;123:1367-84. Bayard M, et al. Nonalcoholic fatty liver disease 2006;73:1961-8. Giboney PT. Mildly elevated liver transaminase levels in the asymptomatic patient. Am Fam Physician 2005;71:1105-10. Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician 1999;59: