Abnormal LTs 2014

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Abnormal Liver Abnormal Liver Tests: Tests:

work-up and work-up and diagnosisdiagnosisRobert G. Gish MDRobert G. Gish MD

Professor Consultant Professor Consultant

Stanford UniversityStanford University

Thank you to: Thank you to:

Carrie Frenette for the great cases !Carrie Frenette for the great cases !

Differential DiagnosisDifferential Diagnosis

Population based survey in US 1999-Population based survey in US 1999-2002 estimated abnormal ALT in 2002 estimated abnormal ALT in 8.9% of population8.9% of population

Symptomatic vs Asymptomatic?Symptomatic vs Asymptomatic? Acute vs Chronic?Acute vs Chronic? Hepatitic vs Cholestatic?Hepatitic vs Cholestatic?

Differential DiagnosisDifferential DiagnosisHepatitic:Hepatitic: Viral Hepatitis: A, B, C, Viral Hepatitis: A, B, C,

D, ED, E Alcoholic and Alcoholic and

Nonalcoholic Nonalcoholic SteatohepatitisSteatohepatitis

AutoimmuneAutoimmune HemachromatosisHemachromatosis Wilson’s diseaseWilson’s disease Alpha-1 antitrypsinAlpha-1 antitrypsin

Cholestatic:Cholestatic: ObstructionObstruction

Gallstones, malignancy, Gallstones, malignancy, parasitesparasites

Primary Biliary CirrhosisPrimary Biliary Cirrhosis Primary Sclerosing Primary Sclerosing

CholangitisCholangitis Infiltrative diseases: Infiltrative diseases:

metastatic cancer, metastatic cancer, sarcoidosis, amyloidosissarcoidosis, amyloidosis

Either:Either: DrugsDrugs Thyroid disordersThyroid disorders Celiac diseaseCeliac disease Vascular disease: CHF, Budd Chiari Vascular disease: CHF, Budd Chiari

syndrome, Sinusoidal obstructive syndromesyndrome, Sinusoidal obstructive syndrome

Liver Tests “ Liver Panel Liver Tests “ Liver Panel ““ AST, ALTAST, ALT

Alkaline PhosphataseAlkaline Phosphatase GGTGGT

BilirubinBilirubin AlbuminAlbumin Protime/INRProtime/INR

Also: Lactate, glucose, cholesterol, clotting factorsAlso: Lactate, glucose, cholesterol, clotting factors Ammonia very poor liver function test, poor Ammonia very poor liver function test, poor

correlation with HE statuscorrelation with HE status

True “liver function tests”

AST, ALTAST, ALT

Aspartate aminotransferase, alanine Aspartate aminotransferase, alanine aminotransferaseaminotransferase Enzymes that are in the hepatocyte and Enzymes that are in the hepatocyte and

function during gluconeogenesisfunction during gluconeogenesis Leak out of the hepatocytes in times of Leak out of the hepatocytes in times of

injury and can be measured in the seruminjury and can be measured in the serum Normally present in serum at levels ~20-Normally present in serum at levels ~20-

30 U/L30 U/L <30 for men<30 for men <20 for women<20 for women

AST/ALTAST/ALT

AST: AST: liver > cardiac muscle > skeletal muscle > kidney liver > cardiac muscle > skeletal muscle > kidney

> brain > pancreas > lung > leukocytes > > brain > pancreas > lung > leukocytes > erythrocyteserythrocytes

Less specific for liver damageLess specific for liver damage Can increase with strenuous exercise, MICan increase with strenuous exercise, MI

Located in cytosol and mitochondria of hepatocytesLocated in cytosol and mitochondria of hepatocytes Cleared more rapidly than ALTCleared more rapidly than ALT

ALTALT Mainly from cytosol of hepatocytesMainly from cytosol of hepatocytes more specific for liver damagemore specific for liver damage

Alkaline PhosphataseAlkaline Phosphatase Exists in liver in membrane of hepatocyte where Exists in liver in membrane of hepatocyte where

it lines the canaliculusit lines the canaliculus Liver > bone > intestineLiver > bone > intestine PlacentaPlacenta Normally changes with ageNormally changes with age

5 15 25 35 45 55 65 75 85

Other cholestatic Other cholestatic enzymesenzymes

GGT: gamma-glutamyltransferaseGGT: gamma-glutamyltransferase Found in hepatocytes and biliary epithelial Found in hepatocytes and biliary epithelial

cellscells 5’ nucleotidase5’ nucleotidase

Both these enzymes can be used to Both these enzymes can be used to confirm alk phos elevation is coming confirm alk phos elevation is coming from liverfrom liver

GGT is also sensitive to alcohol ingestionGGT is also sensitive to alcohol ingestion

BilirubinBilirubin

Breakdown product of hemeBreakdown product of heme 70-80% of normal production is from 70-80% of normal production is from

breakdown of hemoglobin in senescent RBCbreakdown of hemoglobin in senescent RBC Conjugation of bilirubin occurs in ER of Conjugation of bilirubin occurs in ER of

hepatocyte, and conjugated bilirubin is hepatocyte, and conjugated bilirubin is then transported into bile (rate limiting then transported into bile (rate limiting step)step)

Almost 100% of bilirubin in healthy Almost 100% of bilirubin in healthy people is indirectpeople is indirect

BilirubinBilirubin

Increased bilirubin can occur from:Increased bilirubin can occur from: Overproduction of bilirubinOverproduction of bilirubin

Uncomplicated hemolysis (rarely levels >5 mg/dL)Uncomplicated hemolysis (rarely levels >5 mg/dL) Impaired uptake, conjugation, or excretionImpaired uptake, conjugation, or excretion

Gilbert Syndrome, othersGilbert Syndrome, others Blockage of bile ductBlockage of bile duct Regurgitation from damaged hepatocytes of Regurgitation from damaged hepatocytes of

bile ductsbile ducts Hepatocellular damageHepatocellular damage

Urinary bilirubin is only conjugatedUrinary bilirubin is only conjugated

AlbuminAlbumin

Important plasma protein synthesized by Important plasma protein synthesized by the liverthe liver

Half-life 20 daysHalf-life 20 days Levels <3.5 mg/dL should raise the Levels <3.5 mg/dL should raise the

suspicion of chronic liver disease or suspicion of chronic liver disease or inflammatory diseaseinflammatory disease ***not specific for liver disease***not specific for liver disease

Also reduced in heavy alcohol Also reduced in heavy alcohol consumption, chronic inflammation, consumption, chronic inflammation, protein malnutritionprotein malnutrition

Protime/INRProtime/INR Liver synthesizes all major coagulation proteins: I, II, Liver synthesizes all major coagulation proteins: I, II,

V, VII, IX, X, XII, XIIV, VII, IX, X, XII, XII vWF is synthesized in the vascular endothelium, including vWF is synthesized in the vascular endothelium, including

the liverthe liver Protime measured II, VII, IX, X: vitamin K dependent Protime measured II, VII, IX, X: vitamin K dependent

factorsfactors Can be elevated in liver disease or Vitamin K Can be elevated in liver disease or Vitamin K

deficiencydeficiency *** one of the most important abnormalities to signify *** one of the most important abnormalities to signify

development of fulminant hepatic failure in course of development of fulminant hepatic failure in course of acute liver disease, with bilirubin and encephalopathyacute liver disease, with bilirubin and encephalopathy

Degree of elevation is a prognostic factor in many Degree of elevation is a prognostic factor in many liver diseasesliver diseases

Best test for coagulation factors is TEGBest test for coagulation factors is TEG

Evaluation of Abnormal Evaluation of Abnormal Liver TestsLiver Tests

First step is to repeat the test!!First step is to repeat the test!! Many many things can cause a one-time Many many things can cause a one-time

elevation of liver testselevation of liver tests Mild elevations should be monitored for Mild elevations should be monitored for

at least 6 months before a full serologic at least 6 months before a full serologic work-up is donework-up is done Exception is viral hepatitis serologies in Exception is viral hepatitis serologies in

high risk peoplehigh risk people

Evaluate how high the test isEvaluate how high the test is Normal values are calculated from “normal” Normal values are calculated from “normal”

peoplepeople Normal = 2 SD above and below the meanNormal = 2 SD above and below the mean

B y definition, this makes 2.5% of normal people B y definition, this makes 2.5% of normal people have abnormal test!have abnormal test!

Think of situations where a high test is Think of situations where a high test is normalnormal Alk phos in pregnancyAlk phos in pregnancy AST in marathon runnersAST in marathon runners

History History How long has elevation been present?How long has elevation been present? Any symptoms: pruritus, fatigue, RUQ pain, Any symptoms: pruritus, fatigue, RUQ pain,

arthralgias, myalgias, rash, anorexia, fever, arthralgias, myalgias, rash, anorexia, fever, weight loss, changes in urine/stoolweight loss, changes in urine/stool

Symptoms of more severe liver disease: Symptoms of more severe liver disease: jaundice, ascites, LE edema, GI bleeding, jaundice, ascites, LE edema, GI bleeding, confusion or slowed thinkingconfusion or slowed thinking

Other Medical Problems?Other Medical Problems? Family history of liver disease?Family history of liver disease? Personal or family history of autoimmune Personal or family history of autoimmune

disease or thyroid disease?disease or thyroid disease?

Medication HistoryMedication History

What medications do you take?What medications do you take? When did you start them?When did you start them? Any change in doses?Any change in doses?

Over the counter medications?Over the counter medications? Herbals? – ask specifically!!Herbals? – ask specifically!!

Social HistorySocial HistoryEssentialEssential in Eval of liver in Eval of liver

diseasedisease How much do you drink? – be specific!!!How much do you drink? – be specific!!! Any recent travel? Born abroad?Any recent travel? Born abroad? Have you had any blood transfusions?Have you had any blood transfusions? Have you ever had hemodialysis?Have you ever had hemodialysis? Do you work in healthcare? Any needlesticks?Do you work in healthcare? Any needlesticks? Any tattoos?Any tattoos? Have you ever injected drugs, even once?Have you ever injected drugs, even once? Have you ever snorted drugs, even once?Have you ever snorted drugs, even once? Any recent mushroom ingestion?Any recent mushroom ingestion? Any unprotected sex? Multiple sex partners?Any unprotected sex? Multiple sex partners? Are you a Vietnam veteran?Are you a Vietnam veteran?

Physical ExaminationPhysical Examination Look for signs of chronic liver diseaseLook for signs of chronic liver disease

Spider angiomataSpider angiomata Firm liver edgeFirm liver edge SplenomegalySplenomegaly LeukonychiaLeukonychia AscitesAscites LE edemaLE edema Abdominal wall collateral vesselsAbdominal wall collateral vessels Proximal and temporal muscle wastingProximal and temporal muscle wasting

Look for signs of other diseases: acanthosis Look for signs of other diseases: acanthosis nigricans, signs of thyroid disease, nigricans, signs of thyroid disease, xanthomas, LAD, etcxanthomas, LAD, etc Check cardiac exam for JVD, hepatojugular reflexCheck cardiac exam for JVD, hepatojugular reflex

Most of the time, Most of the time, with the history with the history and physical you and physical you

should have a good should have a good idea what’s the idea what’s the

likely culprit of the likely culprit of the elevated liver tests!elevated liver tests!

Case #1Case #1

48 year old man is found to have abnormal 48 year old man is found to have abnormal liver tests on routine physical examinationliver tests on routine physical examination

No significant PMHNo significant PMH On no medicationsOn no medications Tried IV drugs “once in college”Tried IV drugs “once in college” PE normalPE normal Labs: CBC, BMP normalLabs: CBC, BMP normal AST 62, ALT 88, Alk phos 75, Tbil 0.7, INR AST 62, ALT 88, Alk phos 75, Tbil 0.7, INR

1.0, Albumin 4.11.0, Albumin 4.1

Case #1, continuedCase #1, continued

Hepatitis C: Antibody positiveHepatitis C: Antibody positive

What now?What now? Check HCV RNA, genotype, refer to Check HCV RNA, genotype, refer to

hepatologyhepatology

Check other viral serologies alsoCheck other viral serologies also

Hepatitis CHepatitis C

HCV-Ab (hepatitis C antibody)HCV-Ab (hepatitis C antibody) (+) in chronic or previous infection(+) in chronic or previous infection Sensitive screening test with elevated Sensitive screening test with elevated

ALT or age or history of blood exposureALT or age or history of blood exposure Detectable 8-16 weeks after exposure to Detectable 8-16 weeks after exposure to

virusvirus False positives in autoimmune dz or False positives in autoimmune dz or

hypergammaglobulinemiahypergammaglobulinemia False negatives in immunosuppressedFalse negatives in immunosuppressed

Hepatitis C viral level in IU/mlHepatitis C viral level in IU/ml Quant and Qualitative by PCR to < Quant and Qualitative by PCR to <

10-25 IU/ml10-25 IU/ml HCV-RNA detectable 2-4 weeks after HCV-RNA detectable 2-4 weeks after

exposureexposure Level of HCV RNA is a historical Level of HCV RNA is a historical

factor that could predict response to factor that could predict response to Rx but NOT severity of diseaseRx but NOT severity of disease

Case #2Case #245 year old South African 45 year old South African

manman Presents for routine physical and found to Presents for routine physical and found to

have elevated liver testshave elevated liver tests PMH: hyperlipidemiaPMH: hyperlipidemia Soc: drinks 2 beers/week, no Hx drug useSoc: drinks 2 beers/week, no Hx drug use Born in South Africa, came to US in 1985Born in South Africa, came to US in 1985 Family history: none (but he mentions Family history: none (but he mentions

that they don’t go to the doctor)that they don’t go to the doctor) PE: normalPE: normal

manman Labs: CBC, BMP normalLabs: CBC, BMP normal AST 50, ALT 60, Alk phos 70, Tbili AST 50, ALT 60, Alk phos 70, Tbili

0.50.5 INR, Albumin normalINR, Albumin normal US normalUS normal What now?What now?

manman Hepatitis B s Ag: positiveHepatitis B s Ag: positive HBsAb: negativeHBsAb: negative HBcAb: positiveHBcAb: positive What now?What now? HBV DNA 1.5 billion IU/mL, HBeAg HBV DNA 1.5 billion IU/mL, HBeAg

pos, anti-HBe negpos, anti-HBe neg Diagnosis? Diagnosis?

Chronic Hepatitis BChronic Hepatitis B What if HBV DNA was 2000 IU/mL?What if HBV DNA was 2000 IU/mL?

HBsAg Prevalence (%)HBsAg Prevalence (%)

8:8: HighHigh

2-7:2-7: IntermediateIntermediate

<2:<2: LowLow

Global Distribution of Chronic HBV Global Distribution of Chronic HBV InfectionInfection

• 350 million chronic carriers worldwide350 million chronic carriers worldwide• Ninth leading cause of deathNinth leading cause of death• Nearly 75% of HBV chronic carriers are AsianNearly 75% of HBV chronic carriers are Asian

HBV SerologiesHBV SerologiesHBsAHBsAgg

HBsAHBsAbb

HBcAHBcAbb

HBV HBV DNADNA

InterpretationInterpretation

++ -- + + IgMIgM

++ ++ ++ IgGIgG

-- ++ -- ---- ++ ++ ---- -- ++ --

Acute infection

Chronic infection

Immunized

Past Exposure

False pos or Past Exp

HBV SerologiesHBV Serologies HBe Ag: only applicable in patients who HBe Ag: only applicable in patients who

are chronically infected or carriersare chronically infected or carriers Positive: increased infectivityPositive: increased infectivity Negative: precore mutant of virus if DNA Negative: precore mutant of virus if DNA

positive, still can be infective, still has positive, still can be infective, still has advancing diseaseadvancing disease

Levels of HBV DNA important to decide if Levels of HBV DNA important to decide if patient active or inactive with ALT level patient active or inactive with ALT level and imagingand imaging

Case #3Case #319 year old female college 19 year old female college

studentstudent c/o severe fatigue of new onset, jaundice, c/o severe fatigue of new onset, jaundice,

mild pruritus of few days durationmild pruritus of few days duration No EtOHNo EtOH Meds: minocycline, multivitaminMeds: minocycline, multivitamin No Hx of contacts with viral hepatitis, No Hx of contacts with viral hepatitis,

traveltravel PE: heent: mild scleral icterus PE: heent: mild scleral icterus

abd: nl bs, no organomegaly, no abd: nl bs, no organomegaly, no tenderness or palpable masstenderness or palpable mass

Case #3, continuedCase #3, continued

Labs: alb 4.2, t bili 4.2, alk phos 248, Labs: alb 4.2, t bili 4.2, alk phos 248, AST 180, ALT 252; AST 180, ALT 252; CBC normal, BMP normalCBC normal, BMP normal Acute viral hepatitis serologies neg.Acute viral hepatitis serologies neg.

What is the most likely diagnosis?What is the most likely diagnosis?

Case #3Case #319 year old female college 19 year old female college

studentstudent

Drug induced cholestasis Drug induced cholestasis secondary to minocycline.secondary to minocycline.

Symptoms resolved within 2 weeks of Symptoms resolved within 2 weeks of drug d/c, liver profile normalized in drug d/c, liver profile normalized in 8 weeks.8 weeks.

Drug Induced Liver Drug Induced Liver InjuryInjury

Any drug can cause any injury!!!!Any drug can cause any injury!!!! Higher risks in women, older ageHigher risks in women, older age Can be at start of medication, or in Can be at start of medication, or in

some cases at *any time* during some cases at *any time* during therapytherapy

Should rule out other causes of liver Should rule out other causes of liver injuryinjury

Drug Induced Liver Drug Induced Liver InjuryInjury

A note: acetaminophen is the most A note: acetaminophen is the most common cause of DILI, and also the common cause of DILI, and also the most common cause of acute liver failure most common cause of acute liver failure in USin US

Normal dose for acetaminophen toxicity Normal dose for acetaminophen toxicity is 6 to12 grams/d, but toxicity can occur is 6 to12 grams/d, but toxicity can occur in much lower doses in certain in much lower doses in certain circumstances, 2 gm/dcircumstances, 2 gm/d Alcohol useAlcohol use Fasting stateFasting state

Case #4Case #456 year old woman56 year old woman

Presents with fatigue, myalgiasPresents with fatigue, myalgias PMH: hypothyroidism, HTNPMH: hypothyroidism, HTN Meds: Synthroid, Atenolol, MVI, CaMeds: Synthroid, Atenolol, MVI, Ca Soc: no T/E/DSoc: no T/E/D FHx: father with vitiligoFHx: father with vitiligo PE: appears fatigued, Abd with mild PE: appears fatigued, Abd with mild

RUQ tenderness to deep palpationRUQ tenderness to deep palpation

CBC, BMP normalCBC, BMP normal AST 245, ALT 280, TBili 2.0, Alk AST 245, ALT 280, TBili 2.0, Alk

phos 207phos 207 Alb 3.8, INR 1.2Alb 3.8, INR 1.2 US: mild hepatomegaly, otherwise US: mild hepatomegaly, otherwise

normalnormal Differential diagnosis?Differential diagnosis? What further labs?What further labs?

ANA >1:640ANA >1:640 F-actin >1:380F-actin >1:380 Quantitative Ig: Elevated IgGQuantitative Ig: Elevated IgG Viral Markers negativeViral Markers negative

Diagnosis: Autoimmune HepatitisDiagnosis: Autoimmune Hepatitis

Autoimmune HepatitisAutoimmune Hepatitis

Middle-aged (or teenage) woman, Middle-aged (or teenage) woman, non-drinker without viral hepatitisnon-drinker without viral hepatitis

Fatigue, arthralgias/myalgias, Fatigue, arthralgias/myalgias, oligomenorrhea, jaundiceoligomenorrhea, jaundice

Increased AST/ALT, gamma globulinsIncreased AST/ALT, gamma globulins Positive ANA and SMAPositive ANA and SMA Interface hepatitis with Interface hepatitis with

lymphoplasmacytic infiltratelymphoplasmacytic infiltrate Responds to corticosteroidsResponds to corticosteroids

Case #5:Case #5:60 year old man60 year old man

Presents with new onset diabetes, Presents with new onset diabetes, found to have elevated LTsfound to have elevated LTs

PMH: DM II newly diagnosed, OA in PMH: DM II newly diagnosed, OA in hipships

Fhx: noneFhx: none Soc: drinks 3 beers/day, no drug useSoc: drinks 3 beers/day, no drug use PE: normalPE: normal

CBC, BMP normalCBC, BMP normal AST 80, ALT 65, Alk phos 125, TBili 0.6AST 80, ALT 65, Alk phos 125, TBili 0.6 Alb 3.6, INR 1.0Alb 3.6, INR 1.0 US: increased echogenicity of the liverUS: increased echogenicity of the liver

Differential?Differential? Tests?Tests?

Fe % sat 70%, Ferritin 800Fe % sat 70%, Ferritin 800 Viral studies negativeViral studies negative

Differential: ETOH (ASH) vs NAH vs Differential: ETOH (ASH) vs NAH vs HemochromatosisHemochromatosis

or all three ?or all three ?

HFE gene test: C282Y homozygoteHFE gene test: C282Y homozygote

HemochromatosisHemochromatosis Inherited abnormality of iron absorptionInherited abnormality of iron absorption Affects 0.5% of Caucasian peopleAffects 0.5% of Caucasian people

Rare in other racesRare in other races C282Y/H63D gene abnormalitiesC282Y/H63D gene abnormalities

Iron overload seen in C282Y homozygotes and Iron overload seen in C282Y homozygotes and sometimes compound heterozygotes (C282Y/H63D)sometimes compound heterozygotes (C282Y/H63D)

No role for gene testing without elevated iron No role for gene testing without elevated iron tests?tests? Use for family membersUse for family members

Iron tests esp ferritin can be falsely elevated in Iron tests esp ferritin can be falsely elevated in alcohol, acute inflammation, non fasting statealcohol, acute inflammation, non fasting state

Alcoholic Liver DiseaseAlcoholic Liver Disease Seen in 25% of heavy drinkersSeen in 25% of heavy drinkers

>5 drinks/day in men, much lower in women>5 drinks/day in men, much lower in women AST>ALTAST>ALT

AST in mitochondria, and alcohol is a AST in mitochondria, and alcohol is a mitochondrial toxinmitochondrial toxin

Also seen when cirrhosis develops in other Also seen when cirrhosis develops in other diseasesdiseases

Cirrhosis can develop without LT Cirrhosis can develop without LT abnormalities!abnormalities!

Alcohol hepatitis rarely has AST>300sAlcohol hepatitis rarely has AST>300s

Case #6Case #6

A 47 year old Caucasian female A 47 year old Caucasian female presents with complaints of itching, presents with complaints of itching, dry mouth, and RUQ abdominal pain. dry mouth, and RUQ abdominal pain. She also notices some pigmentation She also notices some pigmentation changes on her eyelids. Her medical changes on her eyelids. Her medical history includes frequent UTI’s and history includes frequent UTI’s and osteopenia. osteopenia.

What labs are you most interested in What labs are you most interested in seeing for this patient?seeing for this patient?

Case #6Case #6

You obtain the following labs:You obtain the following labs:

AST=55, ALT=75, Alk Phos=350, AST=55, ALT=75, Alk Phos=350, GGT=110, GGT=110,

AntiNuclear Ab. (ANA) is positiveAntiNuclear Ab. (ANA) is positive

Anti-Mitochondrial Ab. is positiveAnti-Mitochondrial Ab. is positive

What is the diagnosis?What is the diagnosis?

Primary Biliary Primary Biliary CholangitisCholangitis

Destruction of bile ductsDestruction of bile ducts Predominantly womenPredominantly women Ages 30-65Ages 30-65 AMA positive in 95% of casesAMA positive in 95% of cases ANA positive in 60% of casesANA positive in 60% of cases Commonly present with fatigue, Commonly present with fatigue,

prurituspruritus Treatment with Ursodiol can Treatment with Ursodiol can

improve the course of diseaseimprove the course of disease

Extrahepatic Extrahepatic Manifestations of Manifestations of

PBCPBC

Heathcote EJ. Hepatology 2000;31:1005-1013.Kaplan MM. N Engl J Med 1996;335:1570-1580.

Hyperlipidemia

Renal Tubular Acidosis

Fat SolubleVitamin Deficiency

Gallstones

Steatorrhea

Urinary Tract Infections

Osteopenia

Xanthomata

Malignancy

Case #6Case #6

A 55 y.o. male with a history of Ulcerative A 55 y.o. male with a history of Ulcerative Colitis presents with recurrent low-grade Colitis presents with recurrent low-grade fevers, RUQ abdominal pain, pruritus and fevers, RUQ abdominal pain, pruritus and jaundice.jaundice.

Alk Phos is high at 380Alk Phos is high at 380 TBili high at 4.5TBili high at 4.5 AST and ALT are both mildly elevated AST and ALT are both mildly elevated

<100.<100. What test would confirm the diagnosis?What test would confirm the diagnosis? What cancer is this patient at risk for?What cancer is this patient at risk for?

Diagnosis of PSCDiagnosis of PSC

ERCP is most commonly usedERCP is most commonly used Percutaneous cholangiography is Percutaneous cholangiography is

rarely used now because it is rarely used now because it is invasiveinvasive

MRCP is gaining popularity because MRCP is gaining popularity because it is non-invasive, and cost-effectiveit is non-invasive, and cost-effective

PSCPSC

Increased risk for Increased risk for cholangiocarcinomacholangiocarcinoma No role of screening currentlyNo role of screening currently

90+% associated with inflammatory 90+% associated with inflammatory bowel diseasebowel disease More commonly UC than Crohn’sMore commonly UC than Crohn’s

p-ANCA positive in 80%p-ANCA positive in 80%

Case #7Case #7

68 year old Hispanic woman68 year old Hispanic woman Elevated liver tests on routine Elevated liver tests on routine

screeningscreening PMH: DM, HTN, obesityPMH: DM, HTN, obesity Meds: metformin, lisinopril, ASAMeds: metformin, lisinopril, ASA FHx: both parents died of CAD, brother FHx: both parents died of CAD, brother

with DMwith DM PE: acanthosis nigricans on neck, BMI PE: acanthosis nigricans on neck, BMI

Case #7Case #7

AST 85, ALT 120, Alk phos 68, Tbili AST 85, ALT 120, Alk phos 68, Tbili 0.80.8

Alb 4.1, INR 1.1Alb 4.1, INR 1.1 US: increased echogenicity, multiple US: increased echogenicity, multiple

gallstonesgallstones

Diagnosis?Diagnosis?

NASHNASH

Serologically, a diagnosis of exclusionSerologically, a diagnosis of exclusion Abnormal buildup of fat in hepatocytes, Abnormal buildup of fat in hepatocytes,

sometimes causing inflammationsometimes causing inflammation Increasing incidence due to increase in Increasing incidence due to increase in

obesityobesity Risk factors: obesity, hypertriglyceridemia, Risk factors: obesity, hypertriglyceridemia,

HTN, insulin resistance, family historyHTN, insulin resistance, family history Treatment: weight loss, treat risk factorsTreatment: weight loss, treat risk factors Statins are ok to use!!!Statins are ok to use!!!

Other liver diseasesOther liver diseases Alpha-1-antitrypsinAlpha-1-antitrypsin

Abnormal excretion of alpha-1-antitrypsin Abnormal excretion of alpha-1-antitrypsin protein out of hepatocytes: increased buildup protein out of hepatocytes: increased buildup in liver, low levels in lung causing emphysemain liver, low levels in lung causing emphysema

Check Phenotype: ZZ is abnormalCheck Phenotype: ZZ is abnormal Results of a-1-antitrypsin level can change Results of a-1-antitrypsin level can change

with various disease states, so less specificwith various disease states, so less specific Wilson’s diseaseWilson’s disease

Abnormal copper excretionAbnormal copper excretion Low ceruloplasmin (copper binding protein)Low ceruloplasmin (copper binding protein) High 24 hour urine copperHigh 24 hour urine copper Generally young peopleGenerally young people

So what does all So what does all this mean?this mean?

How to evaluate a patient How to evaluate a patient with abnormal LTswith abnormal LTs

Full H&PFull H&P Have patient completely quit ETOHHave patient completely quit ETOH Stop ALL unnecessary medicationsStop ALL unnecessary medications

Emphasize to patient to avoid herbal Emphasize to patient to avoid herbal supplements/teassupplements/teas

If LT abnormalities are low (1-2x ULN)If LT abnormalities are low (1-2x ULN) Recheck Recheck Rule out chronic viral hepatitisRule out chronic viral hepatitis

HBsAg, HBsAb, HBcAb, HCV AbHBsAg, HBsAb, HBcAb, HCV Ab Monitor for 6 monthsMonitor for 6 months

If they remain elevatedIf they remain elevated Check ANA, AMA (if cholestatic), p-ANCA, Check ANA, AMA (if cholestatic), p-ANCA,

quantitative immunoglobulins, Fe studies in quantitative immunoglobulins, Fe studies in Caucasian patients, alpha-1-antitrypsin Caucasian patients, alpha-1-antitrypsin phenotype, ceruloplasmin if patient <45, TSH, phenotype, ceruloplasmin if patient <45, TSH, celiac panel (anti-endomysial Ab, anti-TTG) celiac panel (anti-endomysial Ab, anti-TTG)

If LT abnormalities are ≥3x ULNIf LT abnormalities are ≥3x ULN Check acute viral serologies: HAV IgM, Check acute viral serologies: HAV IgM,

HBsAg, HBsAb, HBcAb (IgM), HCV AbHBsAg, HBsAb, HBcAb (IgM), HCV Ab ANA, ASMA, pANCAANA, ASMA, pANCA AMA if cholestaticAMA if cholestatic Fe studiesFe studies Alpha-1-antitrypsin phenotypeAlpha-1-antitrypsin phenotype Ceruloplasmin if age <45Ceruloplasmin if age <45 Quant IgQuant Ig TSHTSH Celiac PanelCeliac Panel

Every patient needs an imaging Every patient needs an imaging studystudy Ultrasound with doppler flow of portal Ultrasound with doppler flow of portal

vein, hepatic veins, hepatic arteryvein, hepatic veins, hepatic artery If LTs significantly elevated or If LTs significantly elevated or

persistently elevatedpersistently elevated Consider referral to hepatologyConsider referral to hepatology

Questions?Questions?

Abnormal LTs 2014

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