liver function test final (1)
TRANSCRIPT
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Case presentation
Dr syeda shaheera zaidi
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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
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Presenting complaints
• Jaundice------ since childhood
• Generalized weakness--------10 days
• Vomitting-------10 days
• Fever-----------2 days
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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
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• 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
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• 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.
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• 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
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Personal hx
• Sleep: decreased
• Apetite: decreased
• Bowel habits: constipation
• Micturition: normal
• Addiction: nil
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Gynea/ obs hx
• Married for 2 years
• Primary gravida
• No previous abortions/IUD/ still births
• Menstrual hx: normal
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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
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Drug history
• She has been taking syp hepamrez for many years
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socioeconomic
• Belong to low socioeconomic status
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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
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• Aneamia: ++• Jaundice: +++• Edema: +(dorsum of feet, pitting)• dehydration: -ve• Cynosis: -ve• Clubbing: -ve• JVP: not raised• Lymph node: not enlarged• Palmer erythema: -ve
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• Asterexis: -ve
• Scratch mark: -ve
• Thyroid: not palpable
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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
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CNS examination
• GCS: 15/15
• Moving all 4 limbs
• Plantars: bilaterally down going
• SOMI: -ve
• Horizontal nystagmus in both eyes
• Cranial nerves: intact
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chest
• Equal air entery on both sides
• NVB with no added sounds
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CVS
• S1 and s2 audible in all 4 areas
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Differential daignosis
• Acute hepatitis? Hepatitis E
• Heamoglobinopathy
• Congenital hyperbillirubinemia e.g Gilbert’s/ crigler najjar
• Chronic liver disease
• Epilepsy
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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
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• Peripheral film:hypochromic, microcytic, anisocytosis
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UCE
• BUN: 11 mg/dl
• Cr: 0.4mg/dl
• Na: 136meq/l
• K: 3.7meq/l
• Cl: 100meq/l
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LFTs
• Billi T: 27.64mg/dl
• Billi Direct: 3.26 mg/dl
• Billi indirect: 24.38mg/dl
• SGPT: 146U/L
• ALP: 200 U/L
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• RBS: 103 mg/dl
• LDH: 359 U/L
• Uric acid: 4.07 mg/dl
• Retic count: 4.9% ( corrected retic = 2.88%)
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Coagulation profile
• PT: 26.5/26
• APTT: 10.3/10.5
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• Protein total: 5.0g/dl
• Albumin: 2.3 g/dl
• Globulin: 2.7 gm/dl
• A/G ratio: 0.9
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Urine DR
• pH: 6.0
• RBCs: 1-2/hpf
• Pus cells: numerous/hpf
• Protein: ++
• Glucose: -ve
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Viral profile
• HBsAg: -ve
• Anti HCV: -ve
• Anti HAV IgM: -ve
• Anti HEV IgM: -ve
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• MPx3: all –ve
• ICT malaria: -ve (for both vivax and falciparum)
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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
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U/S for fetal well being
• Single alive intrauterine fetus corresponding to 30 weeks+/- 1 week
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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
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• 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
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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
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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
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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
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ABGs
• Fio2: 21%
• pH: 7.50
• PCO2: 26 mm Hg
• PO2: 113 mmHg
• SO2: 99%
• HCO3 :20 meq/l
• ABE: -2
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• Hb electrophoresis -----awaited
• ANA and serum ceruloplasmin-----awaited
• Neuro opinion seeked: plan for MRI brain
• Phenytoin levels sent
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Final diagnosis
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Liver Function Test
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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
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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
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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
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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
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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
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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
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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
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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)
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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 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)
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Prothrombin time
prolonged : • vitamin K deficiency (malnutrition,
malabsorption, antibiotics)• massive transfusion • congenital disease • liver disease (acute as well as
chronic)• warfarin • DIC
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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
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• level of transminase elevation
• predominant AST / ALT elevation
• rate of transaminase declination
AST, ALT
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ALT and AST
• >15 times : acute hepatic injury
• 5-15 times : less useful
• <5 times : chronic hepatic injury
improved acute hepatic injury
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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
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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
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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
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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
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ALT and AST < 5 times and AST predominant
• history alcohol intake (history from patient and family members)
• hemolysis studies
• aldolase
• CPK
• macro-AST
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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
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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)
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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)
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• 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
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Ischemic hepatitis
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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
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Acute biliary obstruction
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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
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RE cell plasma hepatocyte
HEME UCB UCB
+
albumin
UCB+ligandin
bile
urobilinogen stercobilinogen
BilirubinUDP-glucoronyltransferase
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• 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
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Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
hemolysis studies, review medications
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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
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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
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Gilbert’s syndrome
• Dx : – asymptomatic, healthy– mild unconjugated hyperbilirubinemia
(<4 mg/dl) with otherwise normal liver chemistries test
– exclusion medications and hemolysis
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Indirect Hyperbilirubinemia
Bilirubin AST, ALT Alb Glob PT
hemolysis 5 mg/dl increase AST N N N
Gilbert’s syndrome
5 mg/dl normal N N N
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Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
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• 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
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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
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Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubinnormal ALP, ALT, AST
conjugated bilirubinnormal ALP, ALT, AST abnormal ALP, ALT, AST
Rotor’s syndromeDubin-Johnson syndrome
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Diagnostic approach in elevated serum bilirubin
elevated bilirubin
History and PE
unconjugated bilirubin
normal ALP, ALT, AST
conjugated bilirubin
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
/ /
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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
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Physiologic• >60 yr.• child and adolescent• pregnancy• blood group O• post meal (fatty meal)
Pathologic• intrahepatic • extrahepatic
Alkaline phosphatase
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Alkaline phosphatase
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
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Alkaline phosphatase
• 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
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Alkaline phosphatase
• 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
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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
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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
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Alkaline phosphatase
• ALP > 1000 : malignant biliary obstruction, sepsis, AIDS with systemic infection
• decrease : hypothyroidism, pernicious anemia, Zn deficiency, congenital, Wilson’s disease, severe hepatic insufficiency
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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
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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
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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
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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
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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
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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
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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
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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
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Thank You
Piyanant Chonmaitree, MD.Department of Medicine
Srinakharinwirot University