Download Elevated LFT`s – Glover

ELEVATED LFTs
Outpatient
Outpatient Morning Report
7/28/14
Porter Glover, MD
MISNOMER

•
The term is misnomer because it implies that the biochemical tests are solely of hepatic
origin
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 findings
•
There are no well designed randomized controlled trials and few prospective or
retrospective studies directed at evaluation of liver chemistry
AST/ALT
•
AST: 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 males
BILIRUBIN
•
A 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 urine
•
Bilirubin-UGT is expressed shortly after birth and continues to be active and expressed
even in severe liver disease and cirrhosis
Urobilogen: hemolysis, hematoma, cirrhosis, constipation, bacterial
overgrowth
ALKALINE PHOSPHATASE
•
Zinc metalloenzyme present in nearly all tissues, however predominately in bone in liver
(specifically microvilli of bile canaliculus)
•
20% is of intestinal origin
• B and O blood type especially after fatty meals
• Stomach 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 AP
5-NUCLEOTIDASE OR GAMMAGLUTAMYLTRANSFERASE (GGT)
•
Used to confirm liver specific origin for elevation of alkaline phosphatase
•
Present in liver, kidney, pancreas, intestine, and prostate, but not bone
•
Become significantly elevated only in liver diseases such as hepatitis, cirrhosis, and
hepatocellular conditions
INITIAL APPROACH
•
A 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
• Diet
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 Disease
CHRONIC HEPATITIS C
•
Positive 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 individualized
CHRONIC HEPATITIS B
•
0.1-0.2% USA/AUS/West Europe, 10-20% from SE asia and Sub-Sahara Africa
•
Detected by hep B surface antigen
•
Chronic defined as positivity for 6 months
•
Additional studies may include Hep Delta antibodies, Quanitative HBV DNA
•
Ultrasound may be useful
•
Biopsy is recommended
MEDICATIONS
•
Tylenol
•
Alpha-methyldopa
•
Antibiotics (Augmentin/ sulfa)
•
Seizure Meds (Phenytoin/ VA/Carbamazepine)
•
Amiodarone
•
Dantrolene
•
Anti-fungals
•
Statins
•
Isoniazid/Pyrazinamide/Rifampin
•
Protease Inhibitors
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 acutely
ILLICIT DRUGS
•
Anabolic Steroids
•
Cocaine
•
Ecstasy (MDMA)
•
Phencyclidine
TOXINS
•
Carbon Tetrachloride
•
Chloroform
•
Dimethylformamide
•
Hydrazine
•
Hydochlorofluorocarbons
•
2-Nitropropane
•
Trichloroethylene
•
Toluene
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 DM
HEREDITARY HEMACHROMATOSIS
•
Autosomal recessive, mostly northern European decent
•
weakness, fatigue, abdominal pain, arthalgia, impotence
•
Late findings include heart failure, DM, darkening of skin
•
Iron panel for screening (transferrin Sat >45%, Ferritin >1000), then HFE gene testing
•
C282Y/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 spouse
CHRONIC AUTOIMMUNE HEPATITIS
•
Predominately females and associated with thyroid and other autoimmune disorders
•
ANA, ASMA, liver-kidney microsomal ab, IgG
•
Liver Biopsy
OTHER CAUSES
•
Wilson’s- low serum ceruloplasmin, watch out for inflammation, serum and urinary copper
levels, slit-lamp for Kayser-Fleisher rings, Bx is diagnostic
•
Alpha1 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
normal
FAMOUS OLE MISS FOOTBALL PLAYERS
•
Archie and Eli Manning
MILD ELEVATION OF ALT AND AST: <5X ULN AND
AST PREDOMINATE
•
Alcohol-related liver injury
•
Steatosis/steatohepatitis
•
Cirrhosis
ALCOHOL RELATED LIVER INJURY/HEPATITIS
•
Steatoisis 90-100%
•
Hepatitis 10-35%
•
Cirrhosis 8-20%
•
AST: ALT ratio 2:1
•
AST rarely exceeds 300IU/dL
•
Rule out viral, Tylenol and medications at the very least
•
Biopsy not required, results may be similar to NASH
•
Need accurate history---ask Family!!
ELEVATIONS OF AST
•
Hemolysis
•
Myopathy
•
Renal Failure
•
Macro-AST
MODERATE ELEVATIONS 5-15X ULN
•
Virtually the entire spectrum of hepatic diseases
FAMOUS OLE MISS FOOTBALL PLAYERS
•
Current Players in NFL
• Michael Oher- Blind Side
• Patrick Willis- 49ers
• BenJarvus Green Ellis- Bengals
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 B
• E- 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 doppler
ISOLATED UNCONJUGATED
HYPERBILIRUBINEMIA
•
Gilbert’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 exclusion
•
Hemolysis
•
Neonatal Jaundice
•
Crigler-Najjar disease---shortly after birth
•
Resorption of large hematoma
CONJUGATED HYPERBILIRUBINEMIA AND
ALKALINE PHOSPHATASE
•
Bile Duct obstruction
•
Hepatitis
•
Cirrhosis
•
Medications- ABX, Steroids
•
Primary Biliary Cirrhosis
•
Primary Sclerosing Cholangitis
•
Sepsis
•
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
INITIAL APPROACH
•
Repeat levels, GGT
•
Stop possible medication causes
•
Ultrasound for infiltrative or obstructive etiology
• Granulomatous diseases
• Sarcoidosis
• Lymphoma
• Metastatic Disease/ HCC
NEXT
•
If 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 infection
ALBUMIN AND PROTHROMBIN TIME
•
Albumin
• Poor nutritional status
• Severe illness with protein catabolism
• Nephrosis
• Malabsorption
• Prothrombin
• Genetic hematologic abnormalities
• Malabsorption
• Half-life of albumin 19-21 days, coag factors less than a day
- Used in tandem to assess acute vs chronic
MELD SCORE
•
Model 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 app
LIVER TRANSPLANT
Absolute 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 support
Relative Contraindications
• Advanced age- still possible but comprehensive workup for comorbidities
• HIV – although new studies suggest good outcomes in those not infected with HCV
TAKE HOME POINTS
•
Think 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 evaluation
REFERENCES
•
Green 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.gov
DR. MIRKES READING PLEASURE
•
2003 Cotton Bowl Ole Miss 31 Oklahoma State 28
•
2009 Cotton Bowl Ole Miss 21 Oklahoma State 7