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Evaluation of Abnormal Liver Function Tests

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ALT. More specific: elevated in myopathies. Transaminases ... Hepatic: ALT-predominant. Chronic Hep C Hemochromatosis. Chronic Hep B Medications/Toxins ... – PowerPoint PPT presentation

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Title: Evaluation of Abnormal Liver Function Tests


1
Evaluation of Abnormal Liver Function Tests
  • Joshua A. Hodge, Maj, USAF, MC
  • Staff Family Physician
  • Andrews AFB, MD

2
Overview
  • Background
  • Transaminases
  • Alkaline phosphatase
  • Bilirubin
  • Other liver labs
  • Summary

3
Background
  • Liver function tests ordered routinely
  • 1-4 of asymptomatic patients have abnormal
    values
  • Components
  • Transaminases
  • Alkaline phosphatase
  • Bilirubin
  • Others albumin, protein

4
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

5
Transaminases
  • May not be elevated in chronic liver disease
  • HCV- apoptosis
  • Cirrhosis
  • Minimal ALT elevations (
  • Race/Gender
  • Obesity
  • Muscle injury

6
Transaminases
  • Mild elevations more to come
  • Marked elevations
  • Acute toxic injury- ie tylenol, ischemia
  • Acute viral disease
  • Alcoholic hepatitis

7
Transaminases
  • ASTALT ratio
  • Elevated in alcoholic disease
  • 21
  • If AST 500 consider other cause
  • No alcohol use suggests cirrhosis

8
Mild Transaminitis
  • AST/ALT
  • 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

9
Mild Transaminitis
  • Hepatic AST predominant
  • Alcohol
  • Steatosis
  • Cirrhosis
  • Non-hepatic
  • Hemolysis
  • Myopathy
  • Thyroid disease
  • Strenuous exercise

10
Elevated AST ALT,
Hx physical stop hepatotoxic meds
Serologies HAV IgM HBsAg HBcIgM HCV Ab or
RNA
LFTs, PT, albumin, CBC, Hep A/B/C, Fe, TIBC,
Ferritin
Positive serology
Negative serology
Negative serology, asymptomatic
11
Hepatotoxic Medications
  • Analgesics- acetaminophen, NSAIDS
  • Antimicrobials
  • Amox-clav, nitrofurantoin, sulfonamides
  • INH
  • Azoles
  • Protease Inhibitors
  • Anticonvulsants- carbamazepine, valproic acid,
    phenyton

12
Hepatotoxic Medications
  • Cardiovascular- alpha-methyldopa, amiodarone,
    labetalol
  • Hyperglycemics- glyburide, troglidazone
  • Psychiatric- trazadone, disulfiram
  • Heparin
  • Propylthiouracil
  • Statins
  • Zafirlukast

13
Hepatotoxic Herbals
  • Chaparral leaf
  • Ephedra
  • Gentian
  • Germander
  • Jin Bu Huan
  • Senna, Kavakava
  • Scutellaria (skullcap)
  • Shark cartilage
  • Vitamin A

?
14
Negative Serology- Asymptomatic
Stop EtOH meds wt loss glucose control
6 months
Repeat LFTs
Abnormal
Normal
Observation
Ultrasound, ANA, smooth muscle Ab, ceruloplasmin,
antitrypsin, gliadin endomysial Ab
Liver biopsy
?
15
Negative Serology- Clinical Signs/Symptoms of
Liver Disease
Consider ultrasound, ANA, smooth muscle Ab,
ceruloplasmin, antitrypsin
Abnormal
Liver biopsy
?
16
Positive Serologies
Hep C/B infection
? Hep A IgM
Follow clinically, serial LFTs
Observation
Persistent elevated LFTs 6 mos
Clinical improvement, LFTs normalize in Observation
Liver biopsy
17
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

18
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

19
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
anti-HBe
HBeAg
Total anti-HBc
Titre
anti-HBs
IgM anti-HBc
HBsAg
0
4
8
12
16
24
28
32
52
100
20
36
Weeks after Exposure
20
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

21
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

22
Elevated Alk Phos
Abnormal LFTs
Normal LFTs, bili
RUQ u/s for ductal dilatation
GGT or 5-NNT
-

No
Yes
RUQ us, med review, AMA
Other source
ERCP
AMA
Neg
No dilatation
? ALT eval, liver bx, ERCP or MRCP
Observation
Liver bx
? AP 6 mo
23
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

24
Elevated Bilirubin
Conjugated bili Abnormal alk phos, ALT, AST
Unconjugated bili Normal alk phos, ALT, AST
RUQ u/s to assess ductal dilatation
Hemolysis studies, review meds
-

? ALT eval, review meds, AMA, ERCP or MRCP,
liver bx
ERCP or MRCP
25
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

26
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

27
References
  • AGA Clinical Practice Committee. AGA medical
    position statement evaluation of liver
    chemistry tests. Gastroenterology
    20021231364-66.
  • AGA technical review on the evaluation of liver
    chemistry tests. Gastroenterology
    20021231367-84.
  • Bayard M, et al. Nonalcoholic fatty liver
    disease 2006731961-8.
  • Giboney PT. Mildly elevated liver transaminase
    levels in the asymptomatic patient. Am Fam
    Physician 2005711105-10.
  • Johnston DE. Special considerations in
    interpreting liver function tests. Am Fam
    Physician 199959
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