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Evaluation of Abnormal Liver Function Tests

Joshua A. Hodge, Maj, USAF, MC Staff Family Physician Andrews AFB, MD

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

Minimal ALT elevations (<1.5 X normal)


Race/Gender Obesity Muscle injury

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

No alcohol use suggests cirrhosis

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

LFTs, PT, albumin, CBC, Hep A/B/C, Fe, TIBC, Ferritin

Serologies: HAV IgM HBsAg HBcIgM HCV Ab or RNA

Negative serology, asymptomatic

Negative serology

Positive serology

Hepatotoxic Medications
Analgesics- acetaminophen, NSAIDS Antimicrobials
Amox-clav, nitrofurantoin, sulfonamides INH Azoles Protease Inhibitors

Anticonvulsants- carbamazepine, valproic


acid, phenyton

Hepatotoxic Medications
Cardiovascular- alpha-methyldopa,
amiodarone, labetalol Hyperglycemics- glyburide, troglidazone

Psychiatric- trazadone, disulfiram Heparin Propylthiouracil Statins Zafirlukast

Hepatotoxic Herbals
Chaparral leaf Ephedra Gentian Germander Jin Bu Huan Senna, Kavakava Scutellaria (skullcap) Shark cartilage Vitamin A

Negative Serology- Asymptomatic


Stop EtOH & meds; wt loss; glucose control
6 months

Repeat LFTs
Abnormal Normal

Ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin, gliadin & endomysial Ab Liver biopsy

Observation

Negative Serology- Clinical Signs/Symptoms of Liver Disease


Consider ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin
Abnormal

Liver biopsy

Positive Serologies
Hep A IgM + Hep C/B infection Follow clinically, serial LFTs Persistent elevated LFTs > 6 mos

Observation

Clinical improvement, LFTs normalize in <6 mos

Observation

Liver biopsy

Serologic Tests for Viral Hepatitis


HAV
Hep A IgM- in acute infxn Hep A IgG- in previous infxn or vaccination

HCV
HCV Ab- during or after infection HCV-RNA- during infection Detectable prior to HCV Ab turning positive

Serologic Tests for Viral Hepatitis


HBV
Hep B Surface Ag- in active infxn Hep B Surface Ab- in prior infxn or vaccinated Hep B Core Ab IgM- in active infxn Hep B Core Ab IgG- in current or prior infxn HBV-DNA- in active infxn Hep B e Ag & Ab- markers of viral presence and potential infectivity

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course


Symptoms HBeAg anti-HBe

Total anti-HBc

Titre
HBsAg IgM anti-HBc anti-HBs

12 16 20 24 28 32 36

52

100

Weeks after Exposure

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

Antimicrobials- augmentin, erythromycin,


flucloxacillin, TMP-SMX, HIV meds

Cardiovascular- captopril, diltiazem, quinidine Hyperglycemics- chlorpropamide, tolbutamide Psychiatric- fluphenazine, imipramine, iprindole Others- allopurinol, carbamazepine

Elevated Alk Phos


Normal LFTs, bili Abnormal LFTs RUQ u/s for ductal dilatation

GGT or 5-NNT

Other source
No dilatation

+
RUQ us, med review, AMA

Yes

No

ERCP

AMA
Neg

Observation Liver bx
AP > 6 mo

ALT eval, liver bx, ERCP or MRCP

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

RUQ u/s to assess ductal dilatation


Hemolysis studies, review meds

+
ERCP or MRCP

ALT eval, review meds, AMA, ERCP or MRCP, liver bx

Other Liver Labs


Albumin Poor marker of liver function- decreased by trauma, inflammatory conditions, malnutrition Prothrombin time (PT) Insensitive: no change until liver loses 80% capacity Ammonia No correlation between brain & serum values Only one contributor to encephalopathy

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: