72814 Porter Glover MD ELEVATED LFTs Outpatient Misnomer The term is misnomer because it implies that the biochemical tests are solely of hepatic origin LIVER FUNCTIONLIVER CHEMISTRY TESTS ID: 575078
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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 infectionSlide33Slide34
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