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: