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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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Defining TermsDefining Terms
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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Defining TermsDefining Terms
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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Traditional LFTTraditional LFTss
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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Traditional LFTTraditional LFTss
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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Traditional LFTTraditional LFTss
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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Traditional LFTTraditional LFTss
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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Viral HepatitidesViral Hepatitides
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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Viral HepatitidesViral Hepatitides
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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Viral HepatitidesViral Hepatitides
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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Viral HepatitidesViral Hepatitides
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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Viral HepatitidesViral Hepatitides
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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Viral HepatitidesViral Hepatitides
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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Evaluation StrategyEvaluation Strategy
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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Evaluation StrategyEvaluation Strategy
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]