Comprehensive slides on liver function tests

1. LIVER CHEMISTRY
AND FUNCTION
TESTS

2. Uses
• Identifies presence of liver disease
• Type of liver disease-
• Primary hepatocellular
• Cholestatic
• Mixed
• Gauge severity and progression of liver disease
• Monitor therapy response
• Serial LFTs can identify particular cause of disease

3. Limitations
• Total functional capacity of the liver
• Varied biochemical functions
• Individually lack sensitivity and specificity
• Lack of sensitivity (may be normal in cirrhosis or HCC)
• Lack of specificity (aminotransferase levels may be elevated in
musculoskeletal or cardiac disease)
• Results suggest general category of liver disease, not a specific
diagnosis

4. General categories of tests
Tests to detect injury to hepatocytes
Tests of the biosynthetic capacity of the liver
•
•All the enzyme tests
• aminotransferases and alkaline phosphatase
albumin, prothrombin time, ceruloplasmin, ferritin,
alpha 1 antitrypsin, lipoproteins

5. • Tests of the capacity of the liver to transport
organic anions and metabolize drugs
S bilirubin, s bile acids, BSP, indocyanine green (ICG), serum bile acids,
serum caffeine, serum lidocaine metabolites, and breath tests.
• Tests to detect fibrosis in the liver
• Tests for chronic inflammation or altered
immunoregulation
Fibrotest, fibrosure, Enhanced liver fibrosis
Immunoglobulins and specific antibodies

6. Bilirubin metabolism
• Bilirubin, a tetrapyrrole pigment, is a breakdown product of
ferroprotoporphyrin IX (heme).
• Approximately 70% to 80% of the bilirubin produced from the
breakdown of hemoglobin in senescent red blood cells .
• The remainder comes from prematurely destroyed erythroid
cells in bone marrow
• From the turnover of hemoproteins in tissues throughout the
body, mainly liver.
• The initial steps leading to the formation of bilirubin occur in
reticuloendothelial cells, primarily in the spleen and liver.

7. • The first reaction, catalyzed by the microsomal enzyme heme
oxygenase
• oxidatively cleaves the α bridge of the porphyrin group, opens
the heme ring, and produces equimolar amounts of biliverdin
and carbonmonoxide.
• The second reaction, catalyzed by the cytosolic enzyme
biliverdin reductase,
• reduces the central methylene bridge of biliverdin, converting
it to bilirubin .

8. • Bilirubin formed in the reticuloendothelial cells is
lipid-soluble.
• Transported in blood, by reversible, noncovalent
binding to albumin.
• Bilirubin is transported to the liver,
• Taken up by hepatocytes in a process that
involves carrier-mediated membrane transport .

9. • In the hepatocyte, bilirubin is coupled to
glutathione-S-transferases (formerly called
ligandins)
• Bilirubin is then solubilized by means of
conjugation to glucuronic acid.
• Bilirubin monoglucuronide and diglucuronide are
formed, both of which are called direct-acting
bilirubins

10. • The conjugation is catalyzed by an enzyme
system in the endoplasmic reticulum of the
hepatocyte .
• The bilirubin conjugates are then actively
transported from the hepatocyte into canalicular
bile.
• Mediated by an adenosine triphosphate–
dependent transport process.

11. • It is the rate-limiting step in hepatic bilirubin
excretion.
• Mediated by a protein in the bile canalicular
membrane called multidrug resistance–
associated protein 2
• The conjugated bilirubins drain from the bile
duct into the duodenum
• hydrolyzed to unconjugated bilirubin by
bacterial β glucuronidases in the distal ileum and
colon

12. • The unconjugated bilirubin is reduced by normal
intestinal bacteria to colorless tetrapyrroles
called urobilinogens.
• Approximately 80% to 90% of these products are
excreted in feces (unchanged or as urobilins)
• The remaining 10% to 20% of the urobilinogens
are passively absorbed, enter the portal venous
blood.
• A small fraction (<3 mg/dL) is excreted in urine

14. Van den Bergh Reaction
• Serum bilirubin measured in clinical labs by modification of
the diazo reaction.
• The conjugated fraction of bilirubin reacts “directly,” with the
diazo reagent without any accelerant.
• conjugated bilirubin fraction measured by photometric
analysis within 30 to 60 seconds.
• The total bilirubin is measured 30 to 60 minutes after the
addition of an accelerant ( alcohol or caffeine).
• The unconjugated fraction determined by subtracting the
direct component from the total bilirubin

15. Normal values
• Normal values of total serum bilirubin is less than 1.0- 1.5
mg/dl (95% - 0.2-0.9)
• Indirect fraction normal values- 0.8-1.2 mg/dl
• Upper limit of normal for the Direct acting fraction is 30%
• If direct fraction is <15%, bilirubin is entirely indirect.
• Mild increase in conjugated bilirubin in the serum - suspect
liver injury. (0.1 mg/dl)

16. Newer methods
• Newer and more accurate methods of measuring bilirubin( eg
HPLC)
• These new methods allow the identification of delta bilirubin.
• delta bilirubin has the half-life of albumin(14 to 21 days).
• serum bilirubin in some patients with prolonged jaundice
seems to lag behind clinical recovery .
• some patients with conjugated hyperbilirubinemia do not
have bilirubinuria.

17. • Hyperbilirubinemia may result from
• overproduction of bilirubin through excessive breakdown of
hemoglobin;
• impaired hepatocellular uptake,
• conjugation, or excretion of bilirubin;
• or regurgitation of unconjugated and conjugated bilirubin from
damaged hepatocytes or bile ducts.

18. • The presence of conjunctival icterus suggests a
total serum bilirubin level of at least 3.0 mg/dL .
• Does not allow differentiation between
conjugated and unconjugated
hyperbilirubinemia.
• Tea- or cola-colored urine may indicate the
presence of bilirubinuria and thus conjugated
hyperbilirubinemia.

19. • The magnitude and duration of
hyperbilirubinemia have not been critically
assessed as prognostic markers.
• Higher the serum bilirubin level in patients with
viral hepatitis, the greater the hepatocellular
damage .
• Patients may die of acute liver failure with only a
modest elevation of serum bilirubin.
• Total serum bilirubin correlates with poor
outcomes in alcoholic hepatitis

20. Causes of isolated
hyperbilirubinemia in adults
cause Mechanism
Indirect hyperbilirubinemia
Hemolytic disorders
inherited
Red cell enzyme defects (G6PD DEF)
Sickle cell disease
Spherocytosis and elliptocytosis Over production of
Acquired bilirubin
Drugs and toxins
Hypersplenism
Immune mediated/ PNH/ Traumatic

21. Causes of isolated
hyperbilirubinemia in adults
Ineffective erythropoiesis
Cobalamine def
Folate def
Profound iron def
Thalassemia
Drugs – rifampicin/probencid Impaired hepatocellular uptake
Inherited conditions
Crigler- Najjar type 1 and 2/ Gilbert’s
syn
Impaired conjugation of bilirubin
Hematoma Overproduction of bilirubin
DIRECT HYPERBILIRUBINEMIA
Inherited conditions
Dubin- Johnson Syndrome Impaired conjugation of bilirubin
Rotor’s Syndrome

22. Conjugated hyperbilirubinemia
• Bile duct obstruction
• Hepatitis
• Cirrhosis
• Medications/Toxins
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Sepsis
• Total parenteral nutrition
• Isolated
• Dubin-Johnson syndrome
• Rotor syndrome
• Intrahepatic cholestasis of
pregnancy
• Benign recurrent cholestasis
• Vanishing bile duct syndromes

24. Aminotranferases
• The serum aminotransferases are the most sensitive markers
of acute hepatocellular injury .
• catalyze the transfer of the α-amino groups of alanine and l-
aspartic acid, respectively, to the α-keto group of ketoglutaric
acid.
• AST, found in cytosol and mitochondria, is widely distributed
throughout the body.
• ALT, a cytosolic enzyme has the greatest concentration in the
liver.

25. Aminotranferases
• Increases in serum values of the
aminotransferases reflect
• either damage to tissues rich in these enzymes
• changes in cell membrane permeability that allow ALT and AST to
leak into serum
• hepatocyte necrosis is not required for the
release of aminotransferases,
• the degree of elevation of the aminotransferases
does not correlate with the extent of liver injury.

26. Aminotranferases
• They are probably cleared by cells in the reticuloendothelial
system, with AST cleared more rapidly than ALT.

27. • An increased ratio of AST to ALT may also be seen in muscle
disorders.
• The degree of elevation is typically less than 300 U/L.
• In cases of acute muscle injury, the AST/ALT ratio may initially
be greater than 3 : 1
• declines toward 1 : 1 because of the shorter serum half-life of
AST.
• The ratio typically is close to 1 : 1 in patients with chronic
muscle diseases.

28. • AST to ALT ratio is < 1 in patients with chronic
viral hepatitis and NAFLD.
• AST/ALT ratio of greater than 1 as an indicator
of cirrhosis in patients with chronic hepatitis
C.
• The increase in AST/ALT ratio is believed to
result from impaired functional hepatic blood
flow, with a consequent decrease in hepatic
sinusoidal uptake of AST.

29. Causes of elevated serum
aminotransferase levels
Chronic,mild elevations, ALT>AST (<150U/L or 5 × normal)
Hepatic causes
Alpha 1 antitrypsin def
Autoimmune hepatitis
Chronic viral hepatitis
Hemochromatosis
Medications and toxins
Steatosis and steahepatitis
Wilson’s disease
Nonhepatic causes
Celiac disease
hypothyroidism

30. Severe , acute elevations, ALT>AST (1000 U/L or 20 – 25 × normal)
Hepatic causes
Acute bile duct obstruction
Acute Budd- Chiari syndrome
Acute viral hepatitis
Autoimmune hepatitis
Hepatic artery ligation
Ischemic hepatitis
Medications/ toxins
Wilsons disease
Severe, acute elevations, AST>ALT(>1000U/L or >20-25 × normal)
Hepatic causes
Medication and toxins in patient with underlying ALD
Nonhepatic causes
Acute rhabdomyolysis

31. Chronic, mild elevations, AST>ALT(<150 U/L, <5× NORMAL)
Hepatic causes
Alcohol liver injury
cirrhosis
Non-hepatic causes
Hypothyroidism
Macro- AST
Myopathy
Strenous exercise

32. Asymptomatic transaminase
elevations

33. De Ritis Ratio
• Ratio of AST/ALT
•

34. • Alcoholic hepatitis AST> ALT
• Decrease in pyridoxal phosphate leading to decreased ALT
activity
• Mitochondrial damage leading to increased release of mAST
into the serum
• Specificity is increased by measuring mAST/AST ratio
• But AST has a shorter half life and hence the ratio maybe 1 in
alcoholics if measured after a gap after the last binge

35. • PBC and PSC the ratio is >1 but not more than 2
• Acute hepatic toxicities like paracetamol- >2
• DILI- Drugs damaging mitochondria- AST>ALT
cyproterone damaging cytosol ALT>>AST

36. • NAFLD- AST/ALT <1 in morbidly obese patients
• Since obesity and insulin resistance increases ALT levels
• ALT levels predict progression to metabolic syndrome
• Both AST and ALT predict diabetes
• Increased AST/ALT ratio in NASH indicates development of
cirrhosis

37. • Isolated AST elevation
• Hepatic Source with B6 deficiency
• Non- Hepatic source- sample hemolysis
rhabdomyolysis

38. Alkaline Phosphatase
• The term alkaline phosphatase applies to a group
of isoenzymes distributed widely throughout the
body.
• The isoenzymes of greatest clinical importance
in adults are in the liver and bone
• Other isoenzymes originate from the placenta,
small intestine, and kidneys.
• In liver, alkaline phosphatase is found on the
canalicular membrane of hepatocytes;
• Alkaline phosphatase has a serum half-life of
approximately seven days.

39. Alkaline phosphatase
• hepatobiliary disease induces synthesis and leakage
of ALP
• In isolated elevation , the serum GGTP or 5′NT are
used to distinguish a liver origin from bone origin.
• A low serum level may occur in Wilson’s disease,
esp with fulminant hepatitis and hemolysis because
of reduced activity of the enzyme due to
dispacement of zinc by copper
• Low levels also occur in hypothyroidism, perinicious
anemia, Zn def, congenital hypophosphtasia

40. Evaluation of ALP elevations

41. Gamma glutamyl
transpeptidase
• Found in the cell membranes of a wide
distribution of tissues includes
• liver (both hepatocytes and cholangiocytes), kidney,
pancreas, spleen, heart, brain, and seminal vesicles.
• No difference in levels between men and
women and no rise in pregnancy.
• elevated serum GGTP level has high sensitivity
and low specificity for hepatobiliary disease.

42. Gamma glutamyl
transpeptidase
• The primary use is to identify the source of an
isolated elevation in the serum alkaline
phosphatase level.
• GGTP is not elevated in bone disease .
• Elevated in patients taking phenytoin,
barbiturates, and some drugs used in HAART
including NNRT and protease inhibitor
(abacavir).
• Serum GGTP levels are also elevated in alcoholics

43. 5′-Nucleotidase
• Associated with the canalicular and sinusoidal plasma
membranes.
• Also found in intestine, brain, heart, blood vessels, and
endocrine pancreas.
• Levels are unaffected by sex or race, values are lowest in
children.
• Use - Identify the organ source of an isolated serum alkaline
phosphatase elevation .

45. WhenSAPelevationisdetected
Repeat the test
Confirm the hepatic origin
If medications suspected, discontinue them and repeat test
Persistently elevated SAP - evaluate for
•Serum gammaglutamyl transferase
•5´-Nucleotidase
•AP isoenzymes
•Cholestatic liver disease
•Infiltrative liver disease
•Biliary obstruction

46. • AP elevation upto 3 times ULN
• > 3 times ULN
•Nonspecific
•Occurs in all types of liver disorders
•Viral hepatitis
•Cirrhosis
•Infiltrative diseases of the liver
•CHF etc
•Cholestatic disorders Extrahepatic
Intrahepatic
•Infiltrative disorders
•Mets

47. Intrahepatic causes of cholestatic
liver enzyme elevations in adults
Drugs
Bland cholestasis
anabolic steroids
estrogens
Cholestatic hepatitis
ACEI-captopril,enalapril
Azathioprine
Chorpromazine
NSAIDS- Sulindac, piroxicam
Antimicrobials- amox-clav, ketoconazole
Granulomatis hepatitis
Allopurinol
Antibiotics-sulfonamides
Antiepileptics- carbamezepine, phenytoin
CVS agents-hydralazine, procainamide, quinidine
phenylbutazone

48. Intrahepatic causes of cholestatic
liver enzyme elevations in adults
Vanishing bile duct syndrome
Amox-clav
Chlorpromazine
Dicloxacillin
Erythromycin
flucloxacillin
Primary biliary cirrhosis
Primary sclerosing cholangitis
Granulomatis liver disease
brucellosis
fungal- histoplasmosis, coccidiomycosis
Leprosy
Q-fever
Schistosomiasis
Tuberculosis

49. Intrahepatic causes of cholestatic
liver enzyme elevations in adults
Sarcoidosis
Idiopathic granulomatous hepatitis
Viral hepatitis
Hepatitis A,B,C, EBV, CMV
Idiopathic adult ductopenia
Genetic conditions
PFIC 1,2,3
BRIC TYPE1,2
MALIGNANCY- HCC,METS
Infiltrative liver diseases- amyloidosis
Intrahepatic cholestasis of pregnancy
Total parentral nutrition
GVHD

50. EXTRAHEPATIC CAUSES OF CHOLESTATIC
LIVER ENZYMES IN ADULTS
Intrinsic
Choledocholithiasis
Immune-mediated duct injury
Autoimmune pancreatitis
primary sclerosing cholangitis
Malignancy – ampullary cancer, cholangiocarcinoma
Infections – AIDS Cholangiopathy
CMV
Cryptosporidiosis, microspoidiosis
Parasitic infection- ascariasis
Extrinsic
Malignancy- gall bladder cancer
pancreatic cancer
mets
Mirizzi’s syndrome
Pancreatitis, pancreatic pseudocyst

53. •USS to assess hepatic parenchyma and biliary system
should be part of initial evaluation
•Additional imaging of abdomen if indicated
•CT, MRI, MRCP
•If extrahepatic obstruction evident, ERCP or PTC
•If no obstruction, do AMA (anti-mitochondrial antibody)
•Continued presence of persistently elevated SAP ( > 6
months ) of unknown origin - further evaluation with
imaging and/or biopsy
•Potentially treatable cholestatic and infiltrative diseases
with long asymptomatic periods with mild elevations of AP
being the only finding
Eg PBC, PSC, Sarcoidosis etc

54. TESTS OF HEPATIC SYNTHETIC
FUNCTION
• ALBUMIN
• accounts for 75% of the plasma colloid oncotic
pressure .
• average adult produces approximately 15 g/day.
• The half-life of albumin is 14 to 21 days.

55. ALBUMIN
• Not useful in acute liverinjury.
• levels < 3 g/dL suspect chronic injury.
• excellent marker of hepatic synthetic function in
patients with CLD and cirrhosis
• differential diagnosis of serum
hypoalbuminemia,
• hepatocellular dysfunction,
• malnutrition,
• protein-losing enteropathy or
• nephrotic syndrome,
• chronic systemic inflammatory conditions, and hormonal
imbalances

56. PROTHROMBIN TIME
• Clotting - end result of a complex series of
enzymatic reactions involving clotting factors
• All the factors are produced in liver except
factor VIII- produced by vascular endothelial
cells.
• P.T is a measure of the rate at which
prothrombin is converted to thrombin,
• Reflects the extrinsic pathway of coagulation.
• Factors involved in the synthesis of prothrombin
include II, V, VII, and X.

57. International normalized ratio
(INR)
• used to express the degree of anticoagulation on
warfarin therapy.
• standardizes prothrombin time measurement
according to the characteristics of the
thromboplastin reagent used in a particular lab.
• the initial measurement is expressed as an
international sensitivity index (ISI), which is then
used in calculating the INR.
• concern has been raised about the validity of
using the ISI (and INR) in patients with chronic
liver disease.

58. • Causes of prolonged P.T
• hepatic dysfunction,
• congenital deficiency of clotting factors,
• vitamin K deficiency (vitamin K is required for normal functioning
of factors II, VII, IX, and X)
• disseminated intravascular coagulation (DIC).
• DIC identified by measuring a factor VIII level
in serum.
• Vitamin K deficiency -subcutaneous
administration of vit K (e.g., 10 mg) leads to
improvement in P.T by 30%.

59. • P.T most useful in cases of acute liver disease.
• Allows an assessment of current hepatic synthetic function;
• Factor VII has the shortest serum half-life (six hour).
• Prognostic value in acute acetaminophen- and non-
acetaminophen-related liver failure , alcoholic hepatitis .
• INR, component of the MELD score

60. TESTS TO DETECT HEPATIC
FIBROSIS
• liver biopsy is the standard for the assessment
of hepatic fibrosis.
• noninvasive measures of hepatic fibrosis have
been developed.
• measures include single serum biochemical
markers and multiparameter tests aimed at
detecting and staging the degree of hepatic
fibrosis.
• hyaluronan is the best to date

61. Hyaluronan
• Hyaluronan is a glucosaminoglycan produced in mesenchymal
cells .
• Typically degraded by hepatic sinusoidal cells,
• serum levels of hyaluronan are elevated in patients with
cirrhosis as a result of sinusoidal capillarization .
• A fasting hyaluronan level greater than 100 mg/L had a
sensitivity of 83% and specificity of 78% for the detection of
cirrhosis.
• useful for identifying advanced fibrosis in patients with
chronic hepatitis C, chronic hepatitis B, ALD, and
NASH

62. FibroTest & FIBROSpect II
• FibroTest ( FibroSure in the United States) is the best
evaluated of the multiparameter blood tests.
• It incorporates haptoglobin, bilirubin, GGTP, apolipoprotein A-
I, and α2-macroglobulin.
• High positive & negative predictive values for diagnosing
advanced fibrosis chronic hepatitis C.
• The newer FIBROSpect II assay incorporates hyaluronate,
tissue inhibitor of metalloproteinase 1, and α2-macroglobulin.
• Sensitivity of 72% & specificity of 74% for identifying advanced
fibrosis in chronic hepatitis c.

63. Transient elastography (TE),
• Uses ultrasound waves to measure hepatic stiffness
noninvasively.
• The ultrasound transducer emits a low-frequency (50 Hz)
shear wave.
• Amount of time required for the wave to go through a set
“window” of tissue is measured.
• The window of tissue is 1 cm by 4 cm, 100 times the area of an
average liver biopsy.
• Use - to identify advanced fibrosis in patients with
• chronic hepatitis C, PBC, hemochromatosis, NAFLD, and recurrent
chronic hepatitis after liver transplantation

64. Magnetic resonance elastography
(MRE)
• Another noninvasive technique under study.
• low-frequency (65 Hz) waves are transmitted
into the right lobe of the liver.
• The shear elasticity of the liver is measured .
• MRE was found to be superior to TE for staging
liver fibrosis in patients with a variety of chronic
liver diseases

65. QUANTITATIVE LIVER FUNCTION
TESTS
• Evaluate the excretory or detoxification capacity
of the liver more specifically than the serum
bilirubin level.
• lack of specificity and often cumbersome
methodology have limited their widespread
acceptance

66. Metabolic Capacity :
Indocyanine Green ( ICG ) test
14C- Galactose breath test
Microsomal enzyme function :
Aminopurine breath test
Caffeine breath test
Functional hepatic perfusion :
Galactose tolerance test
ICG ( low dose ) test
Microsomal enzyme function and hepatic perfusion :
Lidocaine clearance test

67. Indocyanine green (ICG)
• ICG is a nontoxic dye that is cleared exclusively by the liver;
• 97% of an administered dose (0.64-6.4 mol/kg I.V bolus) is
excreted unchanged into bile.
• ICG can be measured directly by spectrophotometry.
• Noninvasive methods (dichromatic earlobe densitometry and
fingertip optical sensors) appear to correlate well with levels
determined by blood sampling.
• uses of ICG include the
• assessment of hepatic dysfunction,
• measurement of hepatic blood flow,
• and prediction of clinical outcomes in patients with liver
disease.

68. galactose elimination capacity
• studied as a measure of functional hepatic mass.
• Galactose is given as a single intravenous bolus
(0.5 g/kg), and blood samples are collected.
• Patients with cirrhosis and chronic hepatitis have
reduced galactose clearance from serum as
compared with healthy controls

69. Caffeine clearance tests
• Quantify functional hepatic capacity.
• Assessing the activity of cytochrome P450 1A2,
N-acetyltransferase, and xanthine oxidase.
• Caffeine - given orally (200 to 366 mg), and
levels are measured in blood, urine, saliva,
breath, or scalp hair.
• Tobacco use increases caffeine clearance.
• Drug interactions can affect results.
• Increasing age correlates with decreased
caffeine clearance.

70. Lidocaine metabolite formation
• Lidocaine is metabolized to
monoethylglycinexylidide (MEGX) by the hepatic
cytochrome P450 system.
• Serum samples are taken 15, 30, and 60 minutes
after I.V dose of lidocaine (1 mg/kg).
• Not superior to the Child-Turcotte-Pugh (CTP)
or MELD score in predicting prognosis in
cirrhosis sec to viral hepatitis.

71. 14C and 13C aminopyrine breath
tests
• Measures hepatic mixed-function oxidase mass.
• The radioactive methyl groups of aminopyrine undergo
demethylation
• Eventual conversion to labeled CO2, which is then exhaled and
can be measured.
• After an overnight fast, a known dose of 14C aminopyrine
(1 to 2 ? Ci) is administered orally,
• Breath samples are taken every 30 minutes for 4 hours, or
check a single sample at either 1 or 2 hours.
• Healthy subjects excrete 6.6% ? 1.3% of the administered
dose in the breath in two hours.
• Patients with hepatocellular injury excrete considerably less.

72. Bile acids
• Bile acids are synthesized from cholesterol in hepatocytes.
• conjugated to glycine or taurine, and secreted into bile.
• After passage into the small intestine, most bile acids are
actively reabsorbed.
• The liver efficiently extracts bile acids from the portal blood.
• In healthy persons, all bile acids in serum emanate from the
reabsorption of bile acids in the small intestine.
• Maintenance of normal serum bile acid concentrations
depends on hepatic blood flow, hepatic uptake, secretion of
bile acids, and intestinal transit.

73. Bile acids
• Serum bile acids are sensitive but nonspecific indicators of
hepatic dysfunction .
• some quantification of functional hepatic reserve.
• correlate moderately well with the results of aminopyrine
breath tests chronic hepatitis.
• Correlation between serum bile acid levels and the histologic
severity of chronic hepatitis and alcoholic liver disease is poor.
• Elevated in patients with cholestatic liver diseases but normal
in patients with Gilbert's syndrome and Dubin-Johnson
syndrome ..

74. SPECIFIC APPLICATIONS OF LIVER
BIOCHEMICAL TESTING
• Liver biochemical tests have been used to
• monitor for and assess the severity of drug-induced liver injury,
• assess operative risk,
• identify candidates for liver transplantation,
• direct donor organ allocation.

75. Drug-induced liver injury
• Most drugs that are hepatotoxic cause idiosyncratic liver injury
• Defined as injury that is unpredictable, occurs at therapeutic
drug levels, and is infrequent.
• The estimated frequency for any particular medication (1 in
1000 to 1 in 100,000).
• marked by a variable latency period (5 to 90 days, or even
longer).
• Other drugs produce dose-dependent toxicity.
• These injuries are predictable, have a high incidence.

76. Drug-induced liver injury
• Acetaminophen causes dose-dependent liver injury.
• The dose of acetaminophen exceeds 15 g, almost four times
the recommended daily dose, in 80% of cases.
• Therapeutic dose (<4 g/day) can be sufficient to cause liver
injury in susceptible persons.
• Most occurrences of drug-induced liver injury are mild.
• Respond promptly to drug withdrawal with complete
resolution.
• Isolated elevation of the serum aminotransferase levels( 3
times normal), is associated with a positive outcome

77. SURGICAL CANDIDACY AND
ORGAN ALLOCATION
• Patients with acute and chronic liver disease are
potentially at increased risk of morbidity and
mortality .
• The risk depends on the etiology , severity , and
planned operation.
• unexpected elevated liver enzyme levels should
prompt a postponement of surgery.
• Elective surgery should be postponed in patients
with acute hepatitis..

78. SURGICAL CANDIDACY AND
ORGAN ALLOCATION
• The surgical risk in chronic hepatitis
correlates with the severity of histologic
inflammation .
• Only portal inflammation and interface
hepatitis have low operative risk.
• Panlobular hepatitis has an increased risk.
• The etiology of chronic hepatitis does not
influence outcome

79. Assessment of surgical risk in
patients with alcoholic liver
disease.
• Examination of histology is critical .
• Hepatic steatosis alone is associated with a low
operative risk.
• Alcoholic hepatitis is associated with a mortality
rate as high as 55% in patients undergoing
portosystemic shunt surgery .
• A period of abstinence of three to six months
before elective surgery is recommended in these
patients.

80. • Cirrhosis is associated with increased operative
risk, particularly with cardiothoracic surgery,
hepatic resection, and other abdominal
operations.
• The CTP scoring system is useful for predicting
perioperative mortality.

81. Modified Child-Turcotte-Pugh score for grading
severity of liver disease

82. • surgery may be undertaken in patients with Child's class A
cirrhosis,
• whereas the medical condition of patients with Child's class B
cirrhosis should be optimized prior to planned surgery.
• The mortality rate in patients with Child's class C cirrhosis is
prohibitive, and surgery should be avoided.

83. MELD score
• Predicts survival in cirrhosis and portal hypertension
undergoing placement of a transjugular intrahepatic
portosystemic shunt (TIPS).
• validated as an accurate predictor of survival in
advanced liver disease.
• Formula: 9.57 ? loge(creatinine) + 3.78 ? loge(total
bilirubin) + 11.2 ? loge(INR) + 6.43.
• The working range is 6 to 40
• score correlates with mortality in patients undergoing
surgery other than liver transplantation.

84. • MELD is used most often for prioritizing the allocation of
donor organs for liver transplantation.
• Before 2002, organs were allocated by the United Network
for Organ Sharing (UNOS) on the basis of the CTP score and
time on the wait list.