Post on 23-Oct-2015
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
• Wilson’s 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
Positive serologyNegative serologyNegative serology,
asymptomatic
Serologies:HAV IgMHBsAgHBcIgMHCV Ab or RNA
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
☺
Stop EtOH & meds; wt loss; glucose control
Repeat LFTs
ObservationUltrasound, ANA, smooth muscle Ab, ceruloplasmin,
antitrypsin, gliadin & endomysial Ab
Negative Serology- Asymptomatic
Liver biopsy
Abnormal Normal
6 months
☺
Consider ultrasound, ANA, smooth muscle Ab, ceruloplasmin,
antitrypsin
Liver biopsy
Negative Serology- Clinical Signs/Symptoms of Liver Disease
Abnormal
☺
+ Hep C/B infection
Observation
Positive Serologies
Hep A IgM
Follow clinically, serial LFTs
Observation
Persistent elevated LFTs > 6
mo’s
Clinical improvement, LFTs
normalize in <6 mo’s
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
Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titre
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
RUQ us, med review, AMA
Abnormal LFTsNormal LFTs, bili
RUQ u/s for ductal dilatationGGT or 5’-NNT
ALT eval, liver bx, ERCP or
MRCP
Other source
ObservationLiver bx
No dilatation
- +
ERCP AMA
NoYes
Neg
AP > 6 mo
Elevated Alk Phos
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
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
Elevated Bilirubin
+ -
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: