LFT Interpretation

8/11/2019 LFT Interpretation

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Sorting out the DiagnosticsSorting out the Diagnostics

Ed Marino, PAEd Marino, PA--CC

Porter Adventist HospitalPorter Adventist Hospital

Liver Transplant ServicesLiver Transplant Services

Denver, CODenver, CO


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AcknowledgementsAcknowledgements

Thanks to the organizers for my invitationThanks to the organizers for my invitation

EspeciallyEspecially CorinnaCorinna Dan, RN, MPHDan, RN, MPH

Staff at Hepatitis Foundation InternationalStaff at Hepatitis Foundation International

Staff at Porter Hospital Liver TransplantStaff at Porter Hospital Liver TransplantService for allowing me time away for thisService for allowing me time away for this


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Educational ObjectivesEducational Objectives

Review the most common liver lab testsReview the most common liver lab tests

Determine true liver synthetic functionDetermine true liver synthetic function

Review viral hepatitis lab valuesReview viral hepatitis lab values

Discuss follow up for above labsDiscuss follow up for above labs


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The Anatomy of the LiverThe Anatomy of the Liver


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CTCT


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Liver HistologyLiver Histology


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Defining TermsDefining Terms

Hepatitis: refers to any swelling,Hepatitis: refers to any swelling,

inflammation, or irritation of the liverinflammation, or irritation of the liver

Over 100 causes including:Over 100 causes including:Viruses, alcohol, enzyme deficienciesViruses, alcohol, enzyme deficiencies

Iron or copper overload,Iron or copper overload, microvesicularmicrovesicularfatfat

Genetic disorders, licit & illicit drugs, toxinsGenetic disorders, licit & illicit drugs, toxins

Hypotension (shock liver / reperfusion)Hypotension (shock liver / reperfusion)


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Inflammation that lasts long enough willInflammation that lasts long enough will

create fibrosiscreate fibrosisExtreme fibrosis is called cirrhosisExtreme fibrosis is called cirrhosis

Cirrhosis can be either compensated orCirrhosis can be either compensated ordecompensateddecompensated

Compensated cirrhosis can be subtleCompensated cirrhosis can be subtleDecompensatedDecompensated cirrhosis is more obviouscirrhosis is more obvious


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Normal LiverNormal Liver


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Cirrhotic LiverCirrhotic Liver


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Normal Lab Values: 95% of normal,Normal Lab Values: 95% of normal,

asymptomatic patients have numbers inasymptomatic patients have numbers inthis range on athis range on a bell shaped curvebell shaped curve

Abnormal Labs: By definition, 2.5% ofAbnormal Labs: By definition, 2.5% of

normal patients have lab values eithernormal patients have lab values either

above or below theabove or below the normalnormal rangerange


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LiverLiver FunctionFunction TestsTests

ALT: alanine aminotransferase (SGPT)ALT: alanine aminotransferase (SGPT)

AST: aspartate aminotransferase (SGOT)AST: aspartate aminotransferase (SGOT)

Alkaline Phosphatase & BilirubinAlkaline Phosphatase & Bilirubin

Known as LFTKnown as LFTs (but theys (but theyre really not)re really not)


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Liver Synthetic FunctionLiver Synthetic Function

Total Protein and serum albuminTotal Protein and serum albumin

TotalTotal BilirubinBilirubin

Prothrombin Time (PT / INR)Prothrombin Time (PT / INR)

These areThese are truetrue tests of liver functiontests of liver function


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Traditional LFTTraditional LFTss

ALT:ALT:

Found primarily in hepatocytesFound primarily in hepatocytesReleased when cells are hurt or destroyedReleased when cells are hurt or destroyed

Normal levels depend on the referenceNormal levels depend on the referencerange which actually differs lab to labrange which actually differs lab to lab

Considered normal between 5Considered normal between 5--40 U/L40 U/LProbably should be half of this (5Probably should be half of this (5--20?)20?)


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AST:AST:

Found in many sources, including liver,Found in many sources, including liver,heart, muscle, intestine, pancreasheart, muscle, intestine, pancreas

Not very specific for liver diseaseNot very specific for liver diseaseOften follows ALT to a degreeOften follows ALT to a degree

Elevated 2 or 3:1 (vs. ALT) in alcoholicsElevated 2 or 3:1 (vs. ALT) in alcoholicsNormal range: 8Normal range: 8--20 U/L20 U/L


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Alkaline Phosphatase:Alkaline Phosphatase:

Found in liver (especially biliary tract),Found in liver (especially biliary tract),bones, intestines, & placentabones, intestines, & placenta

FractionatedFractionated oror isoenzymesisoenzymes to sourceto sourceLiver AP rises with obstruction orLiver AP rises with obstruction or

infiltrative diseases (i.e., stones or tumors)infiltrative diseases (i.e., stones or tumors)

Normal range: 20Normal range: 20--70 U/L70 U/L


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Bilirubin: two primary sourcesBilirubin: two primary sources

Indirect (unconjugated): old red cells,Indirect (unconjugated): old red cells,removed by the spleen, sent to the liverremoved by the spleen, sent to the liver

LiverLiver addsadds glucuronic acid, making theseglucuronic acid, making these

cells water soluble for excretion; nowcells water soluble for excretion; nowcalled direct (or conjugated)called direct (or conjugated)

Normal range: less than 0.8 mg/dLNormal range: less than 0.8 mg/dL


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Bilirubin: Indirect and directBilirubin: Indirect and direct

Direct (conjugated): Total bilirubin includesDirect (conjugated): Total bilirubin includes

both direct and indirect typesboth direct and indirect types

Excreted in the bile, down the commonExcreted in the bile, down the commonbile duct, into the small intestinebile duct, into the small intestine

Normal range: 0.3Normal range: 0.31.0 mg/ dL1.0 mg/ dL


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Patterns of AbnormalPatterns of Abnormal

Elevations in ALT & AST only: suggestsElevations in ALT & AST only: suggests

cellular injurycellular injury

Elevations in Alk Phos & Bilirubin:Elevations in Alk Phos & Bilirubin:suggests cholestasis or obstructionsuggests cholestasis or obstruction

Mixed pattern: ALT, AST, AP & Bili:Mixed pattern: ALT, AST, AP & Bili:

probably the most common scenarioprobably the most common scenario


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Patterns of AbnormalPatterns of Abnormal

Consider degree of elevation:Consider degree of elevation:

Very high ALT and AST usually only comeVery high ALT and AST usually only comefrom a couple of sources:from a couple of sources:

Acute viral hepatitis (A,B,C, HSV)Acute viral hepatitis (A,B,C, HSV)AcetominophenAcetominophen toxicity / overdosetoxicity / overdose

Shock LiverShock Liver; cardiac or surgical event?; cardiac or surgical event?Most other items donMost other items dont cause huge levelst cause huge levels


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Viral HepatitidesViral Hepatitides

Hepatitis A, B, C, D, E, GHepatitis A, B, C, D, E, G

Cytomeglovirus (CMV)Cytomeglovirus (CMV)

Herpes Virus (HSV)Herpes Virus (HSV)

West Nile Virus (WNV)West Nile Virus (WNV)


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Hepatitis A (HAV):Hepatitis A (HAV):

Food, water borne; heat labileFood, water borne; heat labileFecalFecal -- oral contamination; contagiousoral contamination; contagious

Usually self limited, lasting days to weeksUsually self limited, lasting days to weeks

99% spontaneous recovery, no treatment99% spontaneous recovery, no treatment

Tests: HAV IgM antibody = acute infectionTests: HAV IgM antibody = acute infection

HAV total antibody (HAV total antibody (IgMIgM & IgG) = exposure& IgG) = exposure

only, could be post infection or vaccinationonly, could be post infection or vaccination


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Hepatitis B (HBV):Hepatitis B (HBV):

Blood, semen, saliva, vaginal secretionsBlood, semen, saliva, vaginal secretionsHighly contagious; sexually transmittedHighly contagious; sexually transmitted

9090--95% self limited over 6 months95% self limited over 6 monthsChronic infection: >6 monthsChronic infection: >6 months

DNA virus: incorporates into host withDNA virus: incorporates into host withchronic infectionchronic infection


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HBV Lab Tests:HBV Lab Tests:

HBV s Ag: surface antigen; + infectionHBV s Ag: surface antigen; + infectionHBV s Ab: surface antibody;HBV s Ab: surface antibody; -- infectioninfection

HBV c Ab: core antibody IgM, IgG; onlyHBV c Ab: core antibody IgM, IgG; only+ with infection,+ with infection, notnot vaccinationvaccination

HBV e Ag: envelope antigen; if + activelyHBV e Ag: envelope antigen; if + activelyreplicating virusreplicating virus

HBV DNA: actual viral load in bloodHBV DNA: actual viral load in blood


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Hepatitis C (HCV):Hepatitis C (HCV):

Blood borne, not in food or water; notBlood borne, not in food or water; nothighly sexually transmitted*highly sexually transmitted*

Not highly contagiousNot highly contagious20% self clearing; 80%20% self clearing; 80% chronicitychronicity

RNA virus: doesRNA virus: does notnot incorporate into hostincorporate into hostCan cause HCC; #1 cause of transplantCan cause HCC; #1 cause of transplant


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HCV Ab: + means past exposure; can takeHCV Ab: + means past exposure; can take

33--6 months to form; not found if acute6 months to form; not found if acuteRIBA / ELISA: used to confirm Ab; + rulesRIBA / ELISA: used to confirm Ab; + rulesout false positivesout false positives

HCV PCR RNA: confirms actual viralHCV PCR RNA: confirms actual viralpresence in blood; can be +/presence in blood; can be +/-- or a viralor a viral

count (qualitative vs. quantitative)count (qualitative vs. quantitative)HCV Genotype: there are at least six (6)HCV Genotype: there are at least six (6)different (different (geno)typesgeno)types of HCV virusof HCV virus


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HCV Genotypes: different mutations ofHCV Genotypes: different mutations of

same virus (different branches, same tree)same virus (different branches, same tree)Can vary by global geographyCan vary by global geography

NotNot predicative of damage or symptomspredicative of damage or symptoms

CanCan predict response to treatmentpredict response to treatment

CanCan be used to determine who is the bestbe used to determine who is the best

treatment candidatetreatment candidateG1 & 4: most stubborn; G2 & 3: mostG1 & 4: most stubborn; G2 & 3: most

responsive; G5 & 6: most rareresponsive; G5 & 6: most rare


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Evaluation StrategyEvaluation Strategy

Hepatocellular Injury:Hepatocellular Injury:

Liver biopsy remains theLiver biopsy remains the Gold StandardGold Standardfor diagnosisfor diagnosis

Biopsy is second only to a good historyBiopsy is second only to a good historyIf a biopsy is obtained, youIf a biopsy is obtained, youll need a veryll need a very

experienced pathologist to read itexperienced pathologist to read it

Consider sending it out if your localConsider sending it out if your local

expertise is suspectexpertise is suspect


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Advanced Imaging:Advanced Imaging:

If RUQ US is questionable, and youIf RUQ US is questionable, and yourerelooking at a mixed picture:looking at a mixed picture:

Consider an MRCP: nonConsider an MRCP: non--invasive,invasive,

sensitive forsensitive for ductalductal dilation (CBD,dilation (CBD,pancreatic ducts). Diagnostic, but nonpancreatic ducts). Diagnostic, but non--

therapeutic.therapeutic.ERCP: Therapeutic, risk of pancreatitis,ERCP: Therapeutic, risk of pancreatitis,not available everywherenot available everywhere


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SpiderSpiderAngiomataAngiomata


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Spider NeviSpider Nevi


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Nail ClubbingNail Clubbing


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Dupuytren's Contracture


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AscitesAscites


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Jaundice orJaundice or ScleralScleral IcterusIcterus


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Clinical Pearls:Clinical Pearls:

Acute hepatitis panelsAcute hepatitis panels neverneverconsider acuteconsider acuteHCV. If you have a IVDA pt, consider an HCVHCV. If you have a IVDA pt, consider an HCV

PCR for acute hepatitis C. HIV?PCR for acute hepatitis C. HIV?

Consider celiacConsider celiac spruesprue for abnormal LFTfor abnormal LFTs,s,especially if you get a vague history ofespecially if you get a vague history of

dyspepsia. Order TTG (tissuedyspepsia. Order TTG (tissue transglutaminasetransglutaminase

antibodies) with AGA (antiantibodies) with AGA (anti gliadingliadin antibodies).antibodies).


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SummarySummary

Liver tests are numerous and somewhatLiver tests are numerous and somewhat

confusingconfusingNot all liver disease is associated withNot all liver disease is associated with

abnormal test resultsabnormal test results

Some of the worst liver disease hasSome of the worst liver disease has

relatively normal appearing LFTrelatively normal appearing LFTs and cans and can

only be noticed with a look at syntheticonly be noticed with a look at syntheticfunctionsfunctions

S


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SummarySummary

AllAll abnormal liver tests should beabnormal liver tests should be

investigatedinvestigatedReferral to an expert is absolutely neededReferral to an expert is absolutely needed

Liver biopsy is theLiver biopsy is the Gold StandardGold Standard forfordiagnosisdiagnosis

Family histories of liver disease should beFamily histories of liver disease should be

noted:noted: ..my grandmother died ofmy grandmother died of

cirrhosis, but she never drankcirrhosis, but she never drank..

Th k Y !


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Thank You!Thank You!

My contact information:My contact information:

Ed Marino, PAEd Marino, PA--CCPorter Hospital Liver Transplant ServicePorter Hospital Liver Transplant Service

2535 S. Downing St., Suite #3802535 S. Downing St., Suite #380Denver, CO 80210Denver, CO 80210

[email protected]@centura.orgWk. 303.778.5797 Fax 303.778.5205Wk. 303.778.5797 Fax 303.778.5205
mailto:[email protected]:[email protected]:[email protected]

LFT Interpretation

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