Liver Function Test Final (1)

Case presentation

Dr syeda shaheera zaidi

Bio data

• Name: Sumera w/o Farooq

• Age: 20years

• Occupation: house wife

• Residance: Larkana

• Marital status: married

• Date of admission: 17/07/11

• Mode of admission: emergency

Presenting complaints

• Jaundice------ since childhood

• Generalized weakness--------10 days

• Vomitting-------10 days

• Fever-----------2 days

HX of presenting illness

• The patient has hx of jaundice since 3 months of her life when at that time she gradually developed yellow discoluration of her eyes along with discolouration of urine and some rash but no hx of fever , vomitting, abdominal pain at that time and since than intensity of jaundice varies but never completely resolved. For this complaints pt underwent liver biopsy at the age of 5 years but no record avialable

• The patient also diagnosed as epileptic for 2 years but fit free for 6 months and currently 27 weeks pregnant and was in her usual state of health 15 days back when she developed vomittings. Vomitting usually occur after taking food, yellow in colour, non projectile , not blood stained. No hx of abdominal pain, melena, itching associated but pt initially experienced few episodes of diarrhea

• The pt also has generalized weakness for 15 days and feels difficult to perform daily activities

• The pt also has hx of fever for last 2 days. Fever is low grade, intermittent not associated with chills or rigors.

• Medical: hx of generalized tonic clonic fits for 2 years associated with uprolling of eyes and urinary and fecal incontinance.Fits occur1-2/month but now fit free for last 6 months although took antiepileptic for just 1.5 months

• surgical: not significant

• Blood transfusion:nil

Past history

Personal hx

• Sleep: decreased

• Apetite: decreased

• Bowel habits: constipation

• Micturition: normal

• Addiction: nil

Gynea/ obs hx

• Married for 2 years

• Primary gravida

• No previous abortions/IUD/ still births

• Menstrual hx: normal

Family history

• parents alive and healthy

• 1 of her younger sister(7 years old) also suffering from jaundice since childhood

• 1 sister had some abdominal mass for which she underwent laparotomy

Drug history

• She has been taking syp hepamrez for many years

socioeconomic

• Belong to low socioeconomic status

General physical examination

• Young female of average ht and built, somewhat slow in response but otherwise oriented to time, place and person, looking pale and icteric

• Vitals• BP:120/70• Pulse:120/min• Temp:98.6F• R/R:30/min

• Aneamia: ++• Jaundice: +++• Edema: +(dorsum of feet, pitting)• dehydration: -ve• Cynosis: -ve• Clubbing: -ve• JVP: not raised• Lymph node: not enlarged• Palmer erythema: -ve

• Asterexis: -ve

• Scratch mark: -ve

• Thyroid: not palpable

Abdominal examination

• Distended, no visible veins, striae, pulsations, moving equally with respiration

• HOF :26 weeks

• Liver: edge just palpable

• Spleen: palpable 2-3 cm below costal margin

• No signs of free fluid

• Gut sounds: audible

CNS examination

• GCS: 15/15

• Moving all 4 limbs

• Plantars: bilaterally down going

• SOMI: -ve

• Horizontal nystagmus in both eyes

• Cranial nerves: intact

chest

• Equal air entery on both sides

• NVB with no added sounds

CVS

• S1 and s2 audible in all 4 areas

Differential daignosis

• Acute hepatitis? Hepatitis E

• Heamoglobinopathy

• Congenital hyperbillirubinemia e.g Gilbert’s/ crigler najjar

• Chronic liver disease

• Epilepsy

investigations

• CBC• Hb: 6.7 gm/dl• MCV: 67.8fl• PCV: 26.5%• MCH: 17.0pg• MCHC: 25.2gm/dl• TLC: 8.6 X10e9/l• Neutrophil: 84%• Platelets:370x10E9/L

• Peripheral film:hypochromic, microcytic, anisocytosis

UCE

• BUN: 11 mg/dl

• Cr: 0.4mg/dl

• Na: 136meq/l

• K: 3.7meq/l

• Cl: 100meq/l

LFTs

• Billi T: 27.64mg/dl

• Billi Direct: 3.26 mg/dl

• Billi indirect: 24.38mg/dl

• SGPT: 146U/L

• ALP: 200 U/L

• RBS: 103 mg/dl

• LDH: 359 U/L

• Uric acid: 4.07 mg/dl

• Retic count: 4.9% ( corrected retic = 2.88%)

Coagulation profile

• PT: 26.5/26

• APTT: 10.3/10.5

• Protein total: 5.0g/dl

• Albumin: 2.3 g/dl

• Globulin: 2.7 gm/dl

• A/G ratio: 0.9

Urine DR

• pH: 6.0

• RBCs: 1-2/hpf

• Pus cells: numerous/hpf

• Protein: ++

• Glucose: -ve

Viral profile

• HBsAg: -ve

• Anti HCV: -ve

• Anti HAV IgM: -ve

• Anti HEV IgM: -ve

• MPx3: all –ve

• ICT malaria: -ve (for both vivax and falciparum)

U/S abdomen

• Liver:enlarged, 17.1 cm with decreased echogenecity.

• PV: normal, intrahepatic ducts not dilated

• Gall bladder: sludge and multiple calculi largest measuring 1.0 cm

• CBD: normal

• Spleen:enlrged measuring15.3 cm

U/S for fetal well being

• Single alive intrauterine fetus corresponding to 30 weeks+/- 1 week

Hospital course

• 2nd DOA(18/07/11)

• Pt had episode of GTCs at 12 am for about 20 sec during blood transfusion and she was given inj diazepam and 25% dextrose water

• No spike of fever recorded

• 3rd day of admission(19/07/11)• Pt had another episode of GTCs at 11 am and was

given inj phenytoin as loading dose and serum Ca sent that came out 7.2 mg/dl so inj ca gluconate was also given

• Pt now developed ALOC and GCS droped to 10/15• At 5 pm she suddenly delievered alive fetus and

remained semiconsious• Her chest had bilateral crepts and she was shifted

to ICU considering aspiration

Course in MICU

• Consious level remain same GCS 9/15

• Further episodes of GTCs despite maintainance dosing of phenytoin

• LP was done and inj ceftriaxone 2gm bid started in place of fortum and flagyl

• Blood transfusions given

• LFTs starts improving

CSF DR

• Colourless, Clear, Web not seen

• Protein: 70 mg%

• Glucose: 93 mg%

• Leucocytes: <05/cumm

• Erythrocytes: 1-2/ hpf

• Gram stain: no organism seen

lfts 19/07/11 21/07/11 23/07/11 25/07/11

Billi T 20.68 18.04 11.28 9.76

Billi D 3.63 2.24 1.61 1.22

Billi indirect

17.05 15.08 9.67 8.54

SGPT

ALP

77

158

63

169

36

172

32

165

ABGs

• Fio2: 21%

• pH: 7.50

• PCO2: 26 mm Hg

• PO2: 113 mmHg

• SO2: 99%

• HCO3 :20 meq/l

• ABE: -2

• Hb electrophoresis -----awaited

• ANA and serum ceruloplasmin-----awaited

• Neuro opinion seeked: plan for MRI brain

• Phenytoin levels sent

Final diagnosis

Liver Function Test

Liver Function Test

• interpretation must be performed within the context of the patient’s risk factors, symptoms, concomitant conditions, medications, and physical findings

• rarely provide specific Dx, but rather suggest a general category of liver disease

• differing laboratories differing normal values

Liver Function Test

Mild

(times)

Moderate

(times)

Marked

(times)

AST <2-3 2-3 to 20 >20

ALT <2-3 2-3 to 20 >20

ALP <1.5-2 1.5-2 to 5 >5

GGT <2-3 2-3 to 10 >10

Advantages• sensitive, noninvasive

method of screening liver dysfunction

• pattern of laboratory test abnormalities to recognize type of liver disorder

• assess severity of liver dysfunction

• follow cause of liver disease

Disadvantages• lack sensitivity

– normal results in serious liver disease

• not specific for liver dysfunction

• seldom lead to specific diagnosis

Liver Function Test

Initial Approach

history• patient’s symptoms• risk factors for liver

disease• concomitant conditions• medications • occupational exposure

to hepatotoxins

physical examination • body habitus• splenomegaly• ascites• cutaneous stigmata of

chronic liver disease

•history and physical examination•algorithm approach useful mainly when no clinical clues

classified in 3 groups

•synthetic function : albumin, PT

•hepatocyte injury : AST, ALT

•cholestasis : bilirubin, ALP, GGT

PT, albumin, bilirubin-most common tests used as prognostic factors

Liver Function Test

Liver Function TestLiver 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

Albumin

• depend on nutrition, volume status, vascular integrity, catabolism, hormone, loss in stool and urine

• not specific for liver disease• T1/2 19-21 D

– not reliable indicator of acute liver disease

Hypoalbuminemia

globulin chol/TG Hb

1.decrease synthesis

-protein malnutrition

-chronic liver disease

-chronic inflammation

2.increase loss

-NS

3.increase Vd (ascites, overhydration)

4.increase turnover (catabolic state, steroid)

Globulin

• produced by stimulated B lymphocyte

• elevation in

• chronic liver disease

• chronic inflammation and malignant disease

Prothrombin time

• liver synthesize coagulation factor except FVIII

• most present in excess, clotting abnormality occur only when substantial impairment in ability of liver to synthesis

• PT : FI, II, V, VII, IX and X• T1/2 FVII 6 hrs. (shortest)

Prothrombin time

prolonged : • vitamin K deficiency (malnutrition,

malabsorption, antibiotics)• massive transfusion • congenital disease • liver disease (acute as well as

chronic)• warfarin • DIC

AST and ALT

• most frequent used markers of hepatocellular necrosis, but not correlate with eventual outcome

• decrease : recovery or poor prognosis poor prognosis : rapid fall with rising of

bilirubin and PT

• level of transminase elevation

• predominant AST / ALT elevation

• rate of transaminase declination

AST, ALT

ALT and AST

• >15 times : acute hepatic injury

• 5-15 times : less useful

• <5 times : chronic hepatic injury

improved acute hepatic injury

AST/ALT ratio

• < 1 : majority of liver disease• >2

– extrahepatic source– alcoholic hepatitis– ischemic and toxin – acute Wilson’s disease : hemolysis– cirrhosis

• >4 : fulminant Wilson’s disease

0

10

20

30

40

50

60

70

80

90

alcoholic post necroticcirrhosis

chronichepatitis

obstructivejaundice

viral hepatitis

AST/ALT >1

AST/ALT >2

AST/ALT ratio

Rate of Transaminase Declination

rapid • ischemic• short half life drug• acute biliary tract

obstruction • fulminant hepatitis

slow• acute viral hepatitis• long half life drug• AIH• metabolic disease

ALT and AST < 5 timesALT predominant• Chronic hepatitis B, C• Acute hepatitis (A-E,

EBV, CMV)• Steatohepatitis• Hemochromatosis• Medications/toxins• Autoimmune hepatitis• Alpha1-antitrypsin

deficiency• Wilson’s disease• Celiac disease

AST predominant• Alcohol-related liver injury• Steatohepatitis• Cirrhosis• Drug• Nonhepatic

– Hemolysis– Myopathy– Thyroid disease– Strenuous exercise

*almost any types of liver disease

ALT and AST < 5 times and AST predominant

• history alcohol intake (history from patient and family members)

• hemolysis studies

• aldolase

• CPK

• macro-AST

Alcoholic hepatitis

• appropriate history of alcoholic consumption, serologic exclusion of other liver disease

• ♂ 40-80 g/D, ♀ 20-40 g/D 10-12 yrs.

• characteristic pattern – AST rarely exceeds 300 IU/dl – AST/ALT >1 in 92%, >2 in 70%

• pyridoxine deficiency• alcohol induces release of mitochondrial AST

– GGT/ALP >2.5

ALT and AST > 15 times

• Acute viral hepatitis (A-E, herpes)

• Medications/toxins• Ischemic hepatitis• Acute bile duct

obstruction

• Autoimmune hepatitis

• Wilson’s disease• Acute Budd-Chiari

syndrome• Hepatic artery

ligation • Heat stroke

AST predominate : medication/toxin, ischemic >75 times : ischemic, toxic, viral (less common)

Ischemic hepatitis

• low-flow hemodynamic state– hypotension, sepsis, cardiac arrhythmia,

MI, HF, hemorrhage, extensive burns, severe trauma, heat stroke

• hypotension often not documented

• usually subclinical

(shock liver, acute hepatic circulatory insufficiency)

• sudden and massive (>2000) elevation of liver enzyme, tend to decrease rapidly and return normal within 1 wk.

• mild and transient elevation of bilirubin (80% < 2 mg/dl) and ALP

• extreme elevation LDH (>5000), ALT/LDH < 1.5

• rare acute liver failure • Rx and prognosis α underlying disease

Ischemic hepatitis

Ischemic hepatitis

Acute biliary obstruction

• aminotransferase peak early and decline rapidly over 24-72 hr. despite unresolved obstruction

• after aminotransferase decrease, bilirubin and ALP increase

• 25% of patients with AST > 10X

Acute biliary obstruction

LDH

• non specific

• rhabdomyolysis, MI, hemolysis, stroke, renal infarction, acute or chronic liver disease

• use in – ischemic hepatitis : transient, massive

elevation– malignant infiltration of liver : sustained

elevation with ALP

RE cell plasma hepatocyte

HEME UCB UCB

+

albumin

UCB+ligandin

bile

urobilinogen stercobilinogen

BilirubinUDP-glucoronyltransferase

• Direct bilirubin : reacted directly with reagent

Indirect bilirubin : require addition of alcohol for color development

• Unconjugated bilirubin = indirect form

Conjugated bilirubin = bilirubin mono and di-glucoronides

Bilirubin

Diagnostic approach in elevated serum bilirubin

elevated bilirubin

History and PE

unconjugated bilirubin

normal ALP, ALT, AST

conjugated bilirubin

hemolysis studies, review medications

Isolated unconjugated hyperbilirubinemia

• IDB fraction > 85% of total bilirubin1. increase production :

• hemolysischronic hemolysis-not sustained increase of bilirubin >5 mg/dl in normal hepatic function

• ineffective erythropoiesis : folate, • drug : rifampicin, ribavirin, probenecid• resolution of hematoma

2. defects in hepatic uptake/conjugation• Gilbert’s syndrome• Crigler-Najjar syndrome

Gilbert’s syndrome

• benign, unconjugated hyperbilirubinemia with otherwise normal liver chemistries

• up to 5% of normal population• polymorphism in gene encoding

bilirubin UDP-GTimpair ability to conjugate bilirubin• prominent in fasting state, systemic

illnesses, hemolysis, some medications


• Dx : – asymptomatic, healthy– mild unconjugated hyperbilirubinemia

(<4 mg/dl) with otherwise normal liver chemistries test

– exclusion medications and hemolysis

Indirect Hyperbilirubinemia

Bilirubin AST, ALT Alb Glob PT

hemolysis 5 mg/dl increase AST N N N


5 mg/dl normal N N N


elevated bilirubin

History and PE




• DB > 50% of total bilirubin

• can’t differentiate obstruction and parenchymal disease

• Delta fraction – CB tightly bound to albumin – tendency of hyperbilirubinemia to resolve

more slowly than other biochemical tests

Conjugated hyperbilirubinemia

Conjugated hyperbilirubinemia

• Bile duct obstruction• Hepatitis• Cirrhosis• Medications/Toxins• Primary biliary

cirrhosis• Primary sclerosing

cholangitis• Sepsis• Total parenteral

nutrition

• Intrahepatic cholestasis of pregnancy

• Benign recurrent cholestasis

• Vanishing bile duct syndromes

• Dubin-Johnson syndrome

• Rotor syndrome


elevated bilirubin

History and PE

unconjugated bilirubinnormal ALP, ALT, AST

conjugated bilirubinnormal ALP, ALT, AST abnormal ALP, ALT, AST

Rotor’s syndromeDubin-Johnson syndrome


elevated bilirubin

History and PE




normal ALP, ALT, AST abnormal ALP, ALT, AST

Rotor’s syndrome AST, ALT ALP

Dubin-Johnson syndrome predominate predominate

hemolysis studies, review medications

as elevated

ALT evaluation U/S

ERCP as elevated ALT evaluation

review medications

AMA, ERCP, liver biopsy

present absent

/ /

Alkaline phosphatase

• family of isoenzyme catalyze hydrolysis of No. of P esters at alkaline pH

• require Zn for activity

• present in nearly all tissues (liver, bone, intestinal, placenta, kidney)

• liver ALP– isoenzyme, 5’-nucleotidase, GGT

Physiologic• >60 yr.• child and adolescent• pregnancy• blood group O• post meal (fatty meal)

Pathologic• intrahepatic • extrahepatic



Intrahepaticviral alcohol

drug pregnancy

PBC PSC

TPN sepsis

vanishing bile duct syndrome

benign recurrent cholestasis

benign post-op. cholestasis

paraneoplastic syndrome

venoocclusive disease

GVHD

Extrahepaticintraluminal obstruction :

gall stones, ascariasis,

hemobilia

disease of BD :

PSC, choledochal cyst,

cholangioCA,

AIDS cholangiopathy

external compression :

LN, GB CA, Mirizzi’s syndrome,

CA pancreas, ampullar adenoma


• in biliary obstruction– induction of ALP synthesis 2° to enhanced

translation of mRNA ALP levels, may not rise until 1-2 days

– T1/2 1 wk, take several days for levels to normalise after resolution

• in malignancy ….. • no identifiable liver/bone involvement• biochemical distinct from liver ALP• associated variety of different CA ex lung

CA


• initial evaluation : determine hepatic or nonhepatic origin, concomitant elevation of other serum LFT

• level not a reliable indicator of severity of underlying liver disease

• degree not help to distinguish intrahepatic and extrahepatic

Isolated hepatic ALP elevation

• Partial bile duct obstruction• Medications• Infiltrative liver disease• Hepatic metastasis• PBC• PSC• Hepatitis• Cirrhosis• Vanishing bile duct syndromes• Benign recurrent cholestasis

Infiltrative diseases

• TB• Fungal infection• HCC • Lymphoma• Metastatic malignancy• Amyloidosis • Sarcoidosis • Other granulomatous diseases

modest (up to 3x) rise in aminotransferase,

and up to 20x rise in ALP, bilirubin N-5x


• ALP > 1000 : malignant biliary obstruction, sepsis, AIDS with systemic infection

• decrease : hypothyroidism, pernicious anemia, Zn deficiency, congenital, Wilson’s disease, severe hepatic insufficiency

Medications elevation of bilirubin and ALP

• Anabolic steroid• Allopurinol• Amoxicillin-clavuronic acid• Captopril• Carbamazepine• Chlorpropamide• Cyproheptadine• Diltiazem• Erythromycin• Estrogens• Floxuridine• Flucloxacillin• Fluphenazine

• Gold salts• Imipramine• Indinavir• Iprindole• Nevirapine• Methytestosterone• Methylenedioxymethamphetam

ine• Oxaprozin• Pizotyline• Quinidine• Tolbutamide• TPN• Trimethoprim-

sulfamethoxazole

Diagnostic approach in elevated serum alkaline phosphatase

elevated ALP

History and PE

normal bilirubin, ALT, AST abnormal liver chemistries

GGT or 5’nucleotidase U/S

not hepatobiliary U/S

review medication

AMA

ERCP AMA

liver biopsy observation

as elevated ALT evaluation, liver biopsy, ERCP

negative positive

no duct dilatation

yes no

negative

> 6 months

γ-glutamyltransferase (GGT)

• catalyzed transfer of γ-glutamyl groups of peptides to other amino acid

• abundant in liver, kidney, pancreas, intestine, and prostate, spleen, heart, brain but not in bone

• T1/2 – 7-10 days– 28 days in alcohol-associated liver injury

γ-glutamyltransferase (GGT)

• increase– alcohol – drug

• anticonvulsant (CBZ, phenytoin, and barbiturate), warfarin, OC

– almost all type of liver diseases – COPD, renal failure, DM, hyperthyroidism,

RA, AMI, pancreatic disease

Summary Hepatocellular necrosis Biliary obstruction Infiltration

toxin/ ischemia

viral alcohol complete partial

AST/ALT 50-100X 5-50X 2-5X 1-5X 1-5X 1-3X

ALP 1-3X 1-3X 1-10X 2-20X 2-10X 1-20X

Bilirubin 1-5X 1-30X 1-30X 1-30X 1-5X 1-5X

PT increase in severe,

unresponsive to vit K

increase,

responsive to vit K

normal

albumin increase in subacute/chronic usually normal, decrease in advance

normal

Take home message

• initial evaluation : assess in clinical context

• classified in 3 groups synthetic function : albumin, clotting

time cholestasis : bilirubin, ALP, GGT hepatocyte injury : AST, ALT

misnomer– not effectively assess actual function – not always specific for the liver– limited information regarding presence or

severity of complication

Liver Function Test

Liver Chemistry Test

Liver Function Test

• normal may have abnormal test

• normal value not ensure that patient is free of liver disease

• level of abnormality does not reflect severity but may help in DDx

• decrease in the value does not mean improvement

• limitation in sensitivity and specificity

Thank You

Piyanant Chonmaitree, MD.Department of Medicine

Srinakharinwirot University

Liver Function Test Final (1)

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