Outpatient Morning Report - PowerPoint Presentation

Slide1

Outpatient Morning Report7/28/14Porter Glover, MD

ELEVATED LFTs

OutpatientSlide2

MisnomerThe term is misnomer because it implies that the biochemical tests are solely of hepatic origin

Slide3

LIVER FUNCTION/LIVER CHEMISTRY TESTS

Frequently obtained not only for suspected liver disorders but also for screening asymptomatic individuals such as with periodic health screenings, hospitalizations, and insurance physicals

Abnormal elevations seen in 1-4% of asymptomatic population

Therefore to provide high quality, cost effective heath care interpretation must be done in the context of the patient’s risk factors for disease, symptoms, and historical and physical examination findingsSlide4

There are no well designed randomized controlled trials and few prospective or retrospective studies directed at evaluation of liver chemistrySlide5

AST/ALTAST: cytosol and mitochondria of the liver, however also found abundantly in heart , skeletal muscle, and blood

ALT: cytosol of liver, generally considered specific for hepatocellular injury

Both have diurnal variation and may be affected by exercise

AST may be 15% higher in African-American malesSlide6

BilirubinA

heme

degradation product that is excreted from the body predominately via secretion into bile

Insoluble in water and requires conjugation into the water soluble bilirubin,

and when elevated is seen in the urineBilirubin-UGT is expressed shortly after birth and continues to be active and expressed even in severe liver disease and cirrhosisSlide7

Urobilogen

: hemolysis, hematoma, cirrhosis, constipation, bacterial overgrowthSlide8

Alkaline PhosphataseZinc

metalloenzyme

present in nearly all tissues, however predominately in bone in liver (specifically microvilli of bile

canaliculus

)

20% is of intestinal originB and O blood type especially after fatty mealsStomach and small intestine erosions and ulcerations

During pregnancy rises at late 1

st

trimester and 2X normal by term and remains elevated several weeks after delivery

Liver alkaline phosphatase is more heat stable than bone

Fractionated levels are laboratory specific ( heat,

monoclonal antibodies, wheat germ

lectin

precipitation

Watch out for Germ cell tumors! Placenta-like APSlide9

5-nucleotidase or gamma-glutamyltransferase (GGT)

Used to confirm liver specific origin for elevation of alkaline phosphatase

Present in liver, kidney, pancreas, intestine, and prostate, but not bone

B

ecome significantly elevated only in liver diseases such as hepatitis, cirrhosis, and hepatocellular conditionsSlide10

Initial ApproachA study was done with 19,877 health air force recruits. 99 (0.5%) with elevations and only 12% with identifiable cause

Cost of repeating study is about $30

Extensive serologic workup (iron panel, hepatitis profile, and repeat studies), abdominal ultrasound, liver biopsy would cost $3000

Not all elevations are indicative of progressive liver disease

H&P should consists of Possible Lifestyle etiologies

Alcohol

Medications

Weight

DietSlide11

Mild Elevation of ALT and AST: <5X uLN and ALT predominate (AST 40-200, ALT 68-340)

Chronic Hepatitis C

Chronic Hepatitis B

Acute Viral Hepatitis A-E, EBV, CMV

Steatosis

/Steatohepatitis

(NASH)

Hemochromatosis

Medications/Toxins

Autoimmune Hepatitis

Alpha1-antitrypsin deficiency

Wilson’s Disease

Celiac DiseaseSlide12

Chronic Hepatitis CPositive HCV antibody test

Confirmed with HCV-RNA PCR

Ultrasound/ or other imaging may be useful to visualize liver parenchyma

Liver biopsy to access degree of inflammation and presence of fibrosis or cirrhosis

Serial liver biopsies are controversial, and must be individualizedSlide13

Chronic Hepatitis B0.1-0.2% USA/AUS/West Europe, 10-20% from SE

asia

and Sub-Sahara Africa

Detected by

hep

B surface antigenChronic defined as positivity for 6 monthsAdditional studies may include

Hep

Delta antibodies,

Quanitative

HBV DNA

Ultrasound may be useful

Biopsy is recommendedSlide14

Medications

Tylenol

Alpha-methyldopa

Antibiotics (Augmentin/ sulfa)

Seizure Meds (Phenytoin/ VA/Carbamazepine)

AmiodaroneDantrolene

Anti-

fungals

Statins

Isoniazid/Pyrazinamide/Rifampin

Protease InhibitorsSlide15

Herbs/ALternatives

Chaparral Leaf- anti cancer agent?/Not

Ephedra – banned in 2006

Gentian- bitter root, everything?

Germander- flower treating gallbladder conditions/used in beers- no evidence

Jin Bu Huan- anxiolytic marketed as helpful for liver

Kavakava

- anxiolytic

Scutellaria

(skull cap)- everything, folklore

Shark cartilage- cancer skin conditions

Vitamin A- 50,000IU daily, or 660,000IU acutelySlide16

Illicit drugsAnabolic Steroids

Cocaine

Ecstasy (MDMA)

PhencyclidineSlide17

Toxins Carbon Tetrachloride

Chloroform

Dimethylformamide

Hydrazine

Hydochlorofluorocarbons

2-NitropropaneTrichloroethylene

TolueneSlide18

Hepatic steatosis/Steatohepatitis

(NASH)

Fatty infiltration of the liver with or without associated inflammation

Most common cause of mild liver enzyme elevations

Asymptomatic in 48-100% of patients

Risk factors obesity/

wt

gain/HLD/DM, but may be absent

Ultrasound/ CT/MRI suggests diagnosis

Liver Biopsy confirms and assess degree of inflammation/fibrosis, if elevated 6-12 months

Management includes lifestyle modification

Wt

loss

Exercise

Discontinuation of hepatotoxic medications

Management of hyperlipidemias and DMSlide19

Hereditary Hemachromatosis

Autosomal recessive, mostly northern European decent

weakness, fatigue, abdominal pain,

arthalgia

, impotence

Late findings include heart failure, DM, darkening of skinIron panel for screening (transferrin Sat >45%, Ferritin >1000), then HFE gene testingC282Y/C282Y homozygote most likely, but some C282Y/H63D compound Heterozygotes

Liver Biopsy for those with iron overload and normal HFE analysis

Those with iron overload and positive HFE with normal LFT and Ferritin<1000, no

Bx

Reasonable to screen first degree relatives and spouseSlide20

Chronic Autoimmune HepatitisPredominately females and associated with thyroid and other autoimmune disorders

ANA, ASMA, liver-kidney microsomal

ab

,

IgG

Liver BiopsySlide21

Other causesWilson’s- low serum

ceruloplasmin

, watch out for inflammation, serum and urinary copper levels, slit-lamp for

Kayser

-Fleisher rings,

Bx is diagnosticAlpha1 antitrypsin deficiency- more common than Wilson’s, family

hx

Celiac Disease- abnormal abdominal transaminases,

antiendomysial

,

antigliadin

ab

Acute Viral hepatitis A-E, CMV, EBV, HSV but usually early in course and may be >5X normalSlide22

Famous OlE MISS FOOTBALL PLAYERS

Archie and Eli ManningSlide23

Mild Elevation of ALT and AST: <5X uLN and AST predominate

Alcohol-related liver injury

Steatosis

/

steatohepatitis

CirrhosisSlide24

Alcohol related Liver injury/hepatitis

Steatoisis

90-100%

Hepatitis 10-35%

Cirrhosis 8-20%AST: ALT ratio 2:1

AST rarely exceeds 300IU/dLRule out viral, Tylenol and medications at the very least

Biopsy not required, results may be similar to NASH

Need accurate history---ask Family!!Slide25

Elevations of ASTHemolysis

Myopathy

Renal Failure

Macro-ASTSlide26

Moderate elevations 5-15X uLN

Virtually the entire spectrum of hepatic diseasesSlide27

Famous Ole Miss Football PlayersCurrent Players in NFL

Michael

Oher

- Blind Side

Patrick Willis- 49ers

BenJarvus Green Ellis- BengalsSlide28

Severe ALT and AST elevations >15X ULN: hepatocellular Injury/necrosis, AST >600m ALT>1020

Acute Viral Hepatitis A-E, herpes

A- fecal/oral—supportive care

D- blood/blood contact with confection of

Hep

BE- contaminated food/water in endemic areas, fulminant in pregnancy

Ischemic hepatitis

thrombosis, hepatic artery ligation (

doppler

, angiography)

Hypotension, sepsis, MI, Hemorrhage

Autoimmune hepatitis/

wilsons

- may be mild

Medications/toxins- Tylenol

Acute bile duct obstruction- only transient with stone passage, rare

Acute Budd-

Chiari

syndrome- jaundice/ascites, image hepatic vein with

dopplerSlide29

Isolated Unconjugated HyperbilirubinemiaGilbert’s—5% of population, TATA box polymorphism of UDP-GT. Fasting states, illness, hemolysis, medications

If <4mg/dl with r/o of hemolysis and normal

alk

phos

= diagnosis of exclusionHemolysisNeonatal JaundiceCrigler-Najjar disease---shortly after birth

Resorption of large hematomaSlide30

Conjugated hyperbilirubinemia and Alkaline phosphataseBile Duct obstruction

Hepatitis

Cirrhosis

Medications- ABX, Steroids

Primary Biliary Cirrhosis

Primary Sclerosing CholangitisSepsis

Cholestasis (pregnancy, TPN)

Vanishing bile duct syndrome-

Persistent elevations in serum alkaline phosphatase and bilirubin for more than 6 months after onset of drug induced liver

disease (usually ABX)

Dubin

-Johnson Syndrome/ Rotor Syndrome – impaired hepatocellular secretion Slide31

Initial ApproachRepeat levels, GGT

Stop possible medication causes

Ultrasound for infiltrative or obstructive etiology

Granulomatous diseases

Sarcoidosis

LymphomaMetastatic Disease/ HCCSlide32

NextIf Ultrasound indicates further Imaging needed, CT or MRI or MRCP may be warranted

ERCP is more sensitive than MRCP in evaluation of PSC or other biliary diseases

If extahepatic obstruction is not evident- obtain Anti-mitochondrial

ab

Potentially treatable disease have long asymptomatic periods with elevations of alkaline phosphatase for as long as 6 months

If still no answer, liver biopsy- amyloidosis, TB, Fungal infectionSlide33
Slide34

Albumin and Prothrombin time

Albumin

Poor nutritional status

Severe illness with protein catabolism

Nephrosis

MalabsorptionProthrombin

Genetic hematologic abnormalities

Malabsorption

Half-life of albumin 19-21 days,

coag

factors less than a day

- Used in tandem to assess acute

vs

chronicSlide35

MELD SCOREModel for End Stage Liver Disease- Used to prioritize liver transplant patients with 3 month mortality risk

Fancy formula, INR has most weight, next

creatinine

, bilirubin.

Just use

medcalc phone appSlide36

Liver TransplantAbsolute Contraindications

Cardiopulmonary Disease

Malignancy outside of liver within last 5 years ( not superficial skin cancers)

Active alcohol and drug use

Not within last 6 months

Rehab/abstinence program or social supportRelative Contraindications

Advanced age- still possible but comprehensive workup for comorbidities

HIV – although new studies suggest good outcomes in those not infected with HCVSlide37

Take Home PointsThink outside the liver

Assess values for mild, moderate, severe

All test results must be accessed in clinical context of patient

Consider cost effectiveness

Early referral to GI especially for transplant evaluationSlide38

ReferencesGreen RM, Flamm

S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology. 2002 Oct; 123 (4): 1367-84

www.uptodate.com

Domar

U, Hirano K,

Stigbrand T. Serum levels of human alkaline phosphatase isosymes

in relation to blood groups.

Clin

Chim

Acta

1991 Dec; 203: 305-313

www.altnature.com

www.webmd.com

www.livertox.nih.govSlide39

Dr. Mirkes Reading Pleasure

2003 Cotton Bowl Ole Miss 31 Oklahoma State 28

2009 Cotton Bowl Ole Miss 21 Oklahoma State 7