AbnormalL Liver Function Test 2012

7/29/2019 AbnormalL Liver Function Test 2012

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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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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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Ischaemic- sepsis, hypotension

?most common cause in-patients

Often extremely high >50x

Decrease rapidly

LDH raised 80%

Rarely jaundiced


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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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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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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.

AbnormalL Liver Function Test 2012

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