abnormall liver function test 2012
TRANSCRIPT
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Evaluation of Abnormal Liver
Function Tests
Dr Florencio Dizon
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classified in 3 groups
synthetic function : albumin, PT
hepatocyte injury : AST, ALTcholestasis : bilirubin, ALP, GGT
PT, albumin, bilirubin-most common testsused as prognostic factors
Liver Function Test
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Liver Function Test
Liver chemistry test Clinical implication of abnormality
ALT Hepatocellular damage
AST Hepatocellular damage
Bilirubin Cholestasis, impair conjugation, or biliary obstruction
ALP Cholestasis, infiltrative disease, or biliary obstruction
PT Synthetic function
Albumin Synthetic function
GGT Cholestasis or biliary obstruction
Bile acids Cholestasis or biliary obstruction
5`-nucleotidase Cholestasis or biliary obstruction
LDH Hepatocellular damage, not specific
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Liver Function TestMild
(times)
Moderate
(times)
Marked
(times)
AST 20
ALT 20
ALP 5
GGT 10
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Initial Approach
historypatients symptoms
risk factors for liver disease
concomitant conditions
medicationsoccupational exposure to
hepatotoxins
physical examinationbody habitus
splenomegaly
ascites
cutaneous stigmata of chronicliver disease
history and physical examinationalgorithm approach useful mainly when no
clinical clues
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Albumin
depend on nutrition, volume status, vascularintegrity, catabolism, hormone,
malabsorption, proteinurianot specific for liver disease
T1/2 19-21 D
not reliable indicator of acute liver disease
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Globulin
produced by stimulated B lymphocyte
elevation in
chronic liver disease chronic inflammation and malignant
disease
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Prothrombin timeliver synthesize coagulation factor except
FVIII
most present in excess, clotting abnormal occur
only when substantial impairment in abilityof liver to synthesis
PT : FI, II, V, VII, IX and X
T1/2 FVII 6 hrs. (shortest)prognosis : acute, chronic hepatocellular
disease
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Prothrombin timeprolonged :
vitamin K deficiency (malnutrition,malabsorption, antibiotics)
massive transfusion
congenital disease
liver disease
warfarin DIC
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Prothrombin timein vit K deficiency, vit K 10 mg SC decrease
prolong PT >30% within 24 hrs.
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AST and ALTmost frequent used markers of hepatocellularnecrosis, but not correlate with eventualoutcome
decrease : recovery or poor prognosispoor prognosis : rapid fall with rising of bilirubinand PT
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AST ALTcatalyze transfer aminogroups to form pyruvate catalyze transfer aminogroups to form oxaloacetatecytosol (20%) and
mitochondria (80%) cytosol
T1/2 17 hr. (cytosol)
87 hr. (mitochondria) T1/2 47 hr.liver, cardiac muscle,
skeletal muscle, kidneys,brain, pancreas, lungs,leucocytes, and RBC
low concentration in other
tissues
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level of transminase elevation
predominant AST elevation
rate of transaminase declination
AST, ALT
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ALT and AST>15 times : acute hepatic injury5-15 times : less useful
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AST/ALT ratio< 1 : majority of liver disease
>2extrahepatic source
alcoholic hepatitisischemic and toxin
acute Wilsons disease : hemolysis
cirrhosis
>4 : fulminant Wilsons disease
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Rate of Transaminase
Declinationrapid
ischemic
short half life drugacute biliary tract
obstruction
fulminant hepatitis
slow
acute viral hepatitis
long half life drugAIH
metabolic disease
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Risk factor of chronic viral hepatitis
injection drug use
birth to mother with HBV
blood transfusion prior to 1992
needle stick from a donor subsequently testingpositive for HBV or HCV
chronic hemodialysis
unvaccinated health care workers
homosexual
body piercing or tattooing
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ALT and AST < 5 timesdiscontinue all nonessential medications
if mild elevation and essential medications must
be continuedif liver enzyme elevations continue to rise, suspect
medication should be stopped
long-term effects of chronic, medication inducedhepatotoxicity are lacking for many drugs
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Mild Transaminitis
AST/ALT < 5 times upper limit of normal
Etiologies
Hepatic: ALT-predominant
Chronic Hep C Hemochromatosis
Chronic Hep B Medications/Toxins
Acute viral hep Autoimmune Hep
Steatosis Alpha1 Antitrypsin Def
Wilsons Disease Celiac Disease
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Mild Transaminitis
Hepatic: AST predominant
Alcohol
Steatosis
Cirrhosis
Non-hepatic
Hemolysis
Myopathy Thyroid disease
Strenuous exercise
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Gamma-GThepatocytes and biliary epithelial cells,pancreas, renal tubules and intestine
Very sensitive but Non-specific Raised in ANY liver discease hepatocellular or cholestatic
Usefulness limited
Confirm hepatic source for a raised ALP
Alcohol Isolated increase does not require any further evaluation,
suggest watch and rpt 3/12 only if other LFTs become
abnormal then investigate
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Markers of Cholestasis
ALPliver and bone (placenta, kidneys, intestines orWCC)
Hepatic ALP present on surface of bile duct epithelia andaccumulating bile salts increase its release from cell
surface. Takes time for induction of enzyme levels so may
not be first enzyme to rise and half-life is 1 week.
ALP isoenzymes, 5-NT or gamma GT may be necessary to
evaluate the origin of ALP
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Bilirubin, Albumin and Prothrombin time
(INR) Useful indicators of liver synthetic function
In primary care when associated with liver diseaseabnormalities should raise concern
Thrombocytopaenia is a sensitive indicator of liverfibrosis
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Patterns of liver enzyme alteration
Hepatic vs cholestatic
Magnitude of enzyme alteration (ALT >10x vsminor abnormalities)
Rate of change
Nature of the course of the abnormality (mildfluctuation vs progressive increase)
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Patterns of liver enzyme alteration
Acute hepatitistransaminase > 10x ULN
Cholestatic
Mild rise in ALT
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Acute hepatitis (ALT>10xULN)
Viral
Ischaemic
Toxins
Autoimmune
Early phase of acute obstruction
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Acute hepatitis (ALT>10xULN)
ViralHep A, B, C, E, CMV, EBV
ALT levels usually peak before jaundice appears.
Jaundice occurs in 70% Hep A, 35% acute Hep B,25% Hep C
Check for exposure
Check Hep A IgM, Hep B core IgM andHepBsAg, Hep C IgG or Hep C RNA
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Acute hepatitis (ALT>10xULN)
Ischaemic- sepsis, hypotension
?most common cause in-patients
Often extremely high >50x
Decrease rapidly
LDH raised 80%
Rarely jaundiced
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Acute hepatitis (ALT>10xULN)
Toxins - paracetamol (up to 50% of all cases of
Acute Liver Failure)
Ecstasy ( 2nd
most common cause in the young2 in 70%
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Acute hepatitis (ALT>10xULN)
Autoimmune
Rarely presents with acute hepatitis
Usually jaundiced and progressive liver failure
Raised IgG and autoantibodies (anti-SM, -LKM, -
SLA)
Liver biopsy Steroids and azathioprine
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Acute hepatitis (ALT>10xULN)
Early phase- extrahepatic obstruction/cholangitis
Usually have history of pain
USSdilated CBD ? ERCP or lap chole
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Cholestasis
Isolated ALP 3rd trimester, adolescents
Boneexclude by raised GGT, 5-NT orisoenzymes
May suggest biliary obstruction, chronic liverdisease or hepatic mass/tumour
Liver USS/CT most important investigation-
dilated ducts Ca pancreas, CBD stones, cholangioca or liver
mets
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Cholestasis non-dilated ducts
Cholestatic jaundiceDrugs- Antibiotics, Nsaids,Hormones, ACEI
PBCanti- mitochondrial Ab, M2 fraction, IgM
Chronic liver disease
Cholangiocarcinomabeware fluctuating levels
Primary or Metastatic cancer, lymphoma
Infiltrativesarcoid, inflammatory-PMR, IBD
Liver biopsy often required
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COMMON CAUSES OF
ABNORMAL LFTS Transient mild abnormalities which are
simply impossible to explain
Drugseg Statins
Alcohol excess
Hepatitis C
Non-Alcoholic Fatty Liver Disease
(NAFLD)
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Bilirubin
Product of hemoglobin breakdown
2 Forms
Unconjugated (indirect)- insoluble
in hemolysis, Gilbert syndrome, meds
Conjugated (direct)- soluble
in obstruction, cholestasis, cirrhosis, hepatitis,
primary biliary cirrhosis, etc.
No elevation until loss of > 50% capacity
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Conjugated bili;
Abnormal alk phos,
ALT, AST
Unconjugated bili;
Normal alk phos, ALT,
AST
RUQ u/s to assess ductal
dilatation
Hemolysis studies,
review meds ALT eval,
review meds,
AMA, ERCP or
MRCP, liver bx
ERCP orMRCP
Elevated Bilirubin
+ -
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Abnormal LFTs - Conclusions
Many abnormal LFTs will return to normalspontaneously
An important minority of patients withabnormal LFTs will have importantdiagnoses, including communicable andpotentially life threatening diseases
Investigation requires clinical assessmentand should be timely and pragmatic
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VIRAL HEPATITIS
All exam questions rely on you
understanding that acute infection has IgM
antibodies and chronic has IgG
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Viral Hepatitis
NoneInterferon +Interferon
Ribavirin
IFN
Lamivudine
NONETherapy
NONEHBV vaccineNONEImmune globulin
Recombinan vacc
Immune globulin
Inactivated vacc
Prophylaxis
+++HCCancer
12%
None
520 %
Common
0.1 %
Infect 80-90%
Hepatitis70%
0.11 %
Neonates 90%
Adults 1-10%
0.1 %
None
Clinical
Fulminant
Progression to
chronicity
Fecal - oral+++
+
++
+++
variable
+
Parenteral +++
Perinatal +++
Sexual ++
FecaloralTransmission
AcuteAcute / insidiousInsidiousAcute / insidiousAcuteOnset
6 weeks412 weeks7 weeks412 weeks4 weeksIncubation
HEVHDVHCVHBVHAV
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HEPATITIS A
RNA Virus
Fecal-oral
Incubation 15-50 daysAnti -Hepatitis A IgM present during acute illness.
TX/Prevention: Vaccine, Immune serum globulinfor contacts
Px: Gooddoesnt become chronic rarelyfulminant liver failure.
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HEPATITIS B
DNA Virus
Consists of surface and core
Core consists of Core antigen and e-antigenMost infections are subclinical, but canpresent with arthralgias, glomerulonephritis,
urticariaParenteral or sexual transmission.
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Hepatitis B continued
Hepatocellular necrosis occurs due to the bodys reactionto the virus rather than due to the virus itself
Therefore patients who have a severe illness from hep B
are more likely to clear the virus.SEROLOGY:
Remember Acute infection has IgM chronic has IgG
Anti Core IgM is present during acute phase
Anti Core IgG indicates chronic infection.
Patients with Hep B e Ag have continued active replication
Immunized or previously exposed people have Negative HBsAgand HBeAg, they have IgG Anti HB Core, and Positive anti HepBs and e.
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Serological Patterns of Acute & Chronic Hepatitis B
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Question
A 48 yo woman plans to travel to Mexico with her husband and 11year old child. The family have no known history of liver disease orhepatitis and no members of the family have had immunizations forhepatitis. What immunizations would you recommend:
A. Hepatitis A vaccination for both parents and childB. Hepatitis A Vaccination for parents and child and Hepatitis B
vaccination for the child
C. Hepatitis A and Hepatitis B vaccination for both parents and thechild
D. Screen parents for previous Hep A infection, and recommend Hep Avaccination for the child
E. Screen all members of the family for Hep A and B exposure.
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ANSWER B
All children should now get Hep B.
vaccination as babies, if they miss this they
should have catch up vaccination as 11-12year olds
Previous Hep A infection is unlikely in
children and adults not in high riskpopulations therefore it is safe to vaccinate
without antibody testing.
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QUESTION
A 40 yo married man with two children was recently evaluated for fatigue andelevations of liver function tests and was found to have chronic Hep B. Physicalexamination reveals a few spider angiomata on his chest and upper extremities.
Labs:
HBsAg Pos
HBeAg Pos
HBV DNA 90 (low)
ALT 156 U/L
Albumin 3.8
INR 1.5
A liver biopsy is performed and shows cirrhosis with moderate inflammatory activityThe most appropriate recommendation for this patient is
A. He should receive the Hepatitis A Vaccine
B. His Wife and Childern should receive the Hepatitis B Vaccine
C. He should be treated with Interferon Alpha
D. All of the above
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ANSWER: D
All patients with Liver disease should have the Hepatitis Avaccine as they have decreased hepatic reserve and themortality of Hepatitis A in a patient with Hepatitis B is
considerably increasedHousehold contacts of patients with Hepatitis B should bevaccinated
Patients with HBeAg are candidates for Interferon therapy,this is most likely to benefit patients with HBV DNA
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Hepatitis C
RNA virus
Blood bourne ie. Transmission from IV drug useand transfusion of blood products prior to 1990.
Can also be transmitted by snorting cocaine.
Sexual transmission is low.
Testing involves Anti HCV Antibody, and then
viral load if positive.85% of patients develop chronic infection.
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Complications of Hep C
Cirrhosis
Hepatocellular carcinoma
Cryoglobulinaemia
Prophyria cutanea tarda
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Management of Hep C
Interferon alpha with ribavirin for 6 to 12months clears virus in approx 40% of
patients.There is an algorithm which is used todecide who is treated, but basically anyonewith Hep C, high ALT and less than 40 yo.
If older than 40 should have biopsy firstwhich should at least show periportalinflammation or fibrosis.
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Other issues re. Hep C
Once pt with Hep C is cirrhotic their risk of
developing hepatocellular Ca is 1-4% per
yearAlcohol increases risk
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Other viral hepatitis
Hep E: Acute hepatitis just like hep A
unless you are PREGNANT in which case
can progress to fulminant hepatitisEBV, CMV, Herpes viruses can all cause
acute hepatitis especially in
immunocompromised.
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QuestionA 38 yo woman was found to be Hep C positive 6 months ago after evaluation
for raised AST. The infection was attributed to blood transfusions receivedduring a car accident 15 years ago. She was pleased to learn last month that sheis pregnant with her first child.
The physical examination is within normal limits
She would like further information concerning her prognosis and the risk oftransmission of HCV to her husband and her child.
All of the following statements about HCV infection are true except:A. The chance of transmission of HCV to the newborn is low in the 5% range.
B. Barrier precautions including safe sex are recommended for all couples in amonogamous relationship because of high risk of transmission to the partner
C. Low level transmission of Hep C is recognized within households (5-10%), andthe risk for such transmission should be minimized by practices that avoid
blood-blood exposure such as sharing dental implements and razorsD. In patients with Hep C the chance of developing cirrhosis over several decades
is 20-35%
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Answer B
Maternal-fetal HCV transmission is approx 5%,however if mother is co-infected with HIV thenrisk increases to 30%
Risk of sexual transmission between monogamousspouses is also low approx 5%
Transmission can occur between non-sexualhousehold contacts therefore should be told toavoid sharing razors etc.
20-35% of patients with Hep C develop cirrhosis
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Three autoimmune liver
diseasesThey are easily confused:
Autoimmune hepatitis
Primary Biliary Cirrhosis
Primary Sclerosing Cholangitis
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AUTOIMMUNE HEPATITIS
ANA positive
Anti smooth muscle positive
High bilirubin and ALT but normal Alk Phos (cf. Primary
biliary cirrhosis)Presentation: tiredness, anorexia, RUQ pain, cushingoidfacies despite no exogenous steroids. Stigmata of liverdisease
Pathology: Piecemeal necrosis with lymphocyte infiltration
Tx: immunosupression, liver transplant
Complications: All the complications of chronic liverdisease
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Primary Biliary Cirrhosis
Increased Alk phos and Antimitochondrial positive
Damage to intralobular bile ducts by chronic granulomatousinflammation
Associated with other autoimmune diseases (Thyroid, RA, Sjogrens,
Systemic Sclerosis)NB. See granulomas on Bx not piecemeal necrosis
Unable to excrete bile, therefore present with malabsorption of fatsoluble vitamins. And with evidence of portal hypertension.
Present with lethargy, itching and increased Alk Phos in a middleaged
woman.May have hyperlipidaemia
Consider in any patient with autoimmune disease presenting with liverdisease.
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Primary Sclerosing
CholangitisSeen in patients with UC and HIVInflammation, fibrosis and strictures of biliary tree causing Beaded
biliary tree on ERCP
Chronic biliary obstruction leads to cirrhosis
Presentation: Asymptomatic high Alk Phos, Jaundice, pruritis abdopain and fatigue
Dx: High bilirubin and Alk phos but NEGATIVE antimitochondrialAb (Cf. primary biliary cirrhosis)
Mgt: Steroids, Cholestyramine or ursodeoxycholic acid to treat the
pruritis and cholestasis but does not affect disease processLiver transplant for endstage disease but 20% recur.
NB. PSC is independent of activity of UC.