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

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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

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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