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Ran Oren, MD Inst. Gastroenterology & Liver Diseases,Hadassah University Hospital, Jerusalem
Liver Function Tests (& Jaundice)
- בגוף ביותר הגדול 1500האיברגרם
עליונה ימנית בבטן נמצא
הכבד :תפקידי
, ופקטורי קרישה פקטורי לגוף החיוניים חלבונים יצירתגדילה
מהגוף חומרים ולהפרשת לעיכול החשובה מרה יצירת
) , , שומנים ) חלבונים סוכרים המזון אבות ויסות
רעלים סילוק
לפעילות תרופות הפיכת
רגנרציה ויכולת עצומה רזרבהמדהימה
Liver cells• Hepatocyte
• Bile duct epithelial cell
• Stellate cell
• Kupffer cell
• Endothelial cell
Liver diseases
• Acute
• Fulminant
• Chronic
• Cirrhosis
Etiology for liver diseases
• Inflammation• Infectious• Non-infectious
• Metabolic/Genetic
• Neoplasm
• Alcohol/drug induced/NAFLD
• Vascular
• Traumatic
Elevated liver enzymes (1)
• Hepato cellular damage• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Cholestasis• Alkaline posphatase (AP)• Gamma glutamyltrasferase (gamma GT)
Elevated liver enzymes (2)
• TransportTransport• Bilirubin
• Synthetic functionSynthetic function• Albumin, INR
• Fibro-markerFibro-marker• Stage of fibrosis• Fibrodynamics
Liver Function Liver Function TestsTests
• Misnomer (elavated liver enzymes)
• The upper limit of normal range
• The significance of normal serum levels in various diseases (HCV,
HBV, NAFLD)
Questions ?Questions ?• What is “healthy”?
• What is a healthy population?
Total Total PopulationPopulation
50.150.1
0
10
20
30
40
50
“New normal”
37.437.4
Excluding all abnormal Tests
Excluding Abnormal Tests except diabetes and dislipidemia
40.040.0
ALT- 95 ALT- 95 percentilepercentile
ALT- healthy upper limitALT- healthy upper limit
* <0.00001
U/l
5252
Maccabi
N=272,273 N=87,020 N=17,929
Importance of true Importance of true healthy range for ALThealthy range for ALT
Pro’s:
1.Valid indicator for liver disease
2. Early detection of liver disease
Con’s:
1. Economical burden
2. Patient’s anxiety
3. Decrease in blood donors pool
Reevaluation of ALT “normal” Reevaluation of ALT “normal” range => ALT range => ALT healthy healthy range range
• Piton et al, Hepatology, May, 1998-
ALT adjustment by sex and BMI
• Prati et al, Ann. Int. Med., July 2002
Prati et al, Ann. Int. Med., July 2002
• 6835 healthy Italian blood donors.
• Factors associated with ALT Age, BMI, serum cholesterol, triglycerides, glucose, physical exercise
• Healthy ranges of ALT - Low risk for liver disease (HCV) and NAFLD
• New upper limits (95 percentile): Men- 30U/l Women-19U/l
Hepato cellular damage
Elevated liver enzymes
• Acute elevation of transaminasesAcute elevation of transaminases• Chronic elevation of transaminasesChronic elevation of transaminases
in:in:• A patient taking a drug
• Obese patient / Suspected alcoholism
• Celiac disease
• Metabolic diseases
• Bilirubin Transport
• Cholestasis
Elevated liver enzymes
• Acute elevation of transaminasesAcute elevation of transaminases• Chronic elevation of transaminasesChronic elevation of transaminases in:in:
• A patient taking a drug• Obese patient / Suspected alcoholism• Celiac disease• Skin lesions
• Metabolic diseases• Bilirubin Transport• Cholestasis
Causes of chronic elevated
Aminotransferases levelsHepatic:
• Viral hepatitis• NAFLD • Autoimmune• Drug induced• Alcohol• Metabolic
o Hemochromatosiso Wilson’s diseaseo Alpha 1 antitrypsin
Non Hepatic:• Celiac sprue• Muscle diseases• Strenous exercise
Elevated liver enzymes
• Acute elevation of transaminasesAcute elevation of transaminases
• Chronic elevation of transaminasesChronic elevation of transaminases in:in:
• A patient taking a drugA patient taking a drug• Obese patient / Suspected alcoholism• Celiac disease• Skin lesions
• Metabolic diseases
• Bilirubin Transport
• Cholestasis
Elevated liver enzymes
• Acute elevation of transaminasesAcute elevation of transaminases
• Chronic elevation of transaminasesChronic elevation of transaminases in:in:• A patient taking a drug
• Obese patient / Suspected alcoholismObese patient / Suspected alcoholism• Celiac disease
• Metabolic diseases
• Bilirubin Transport
• Cholestasis
Non Alcoholic Fatty Liver Disease?Disease?NAFLDNAFLD
• Is the most common form of liver disease
• Is no longer considered benign• May progress to end-stage liver
disease
Elevated liver enzymes
• Acute elevation of transaminasesAcute elevation of transaminases• Chronic elevation of transaminasesChronic elevation of transaminases
in:in:• A patient taking a drug
• Obese patient / Suspected alcoholism
• Celiac disease
• Metabolic diseases
• Bilirubin Transport
• Cholestasis
Celiac Disease
• Prevalence 1:300
• Should be suspected in cases of idiopathic hypertransaminasemia
Elevated liver enzymes
• Acute elevation of transaminasesAcute elevation of transaminases• Chronic elevation of transaminasesChronic elevation of transaminases
in:in:• A patient taking a drug
• Obese patient / Suspected alcoholism
• Celiac disease
• Metabolic diseases
• Bilirubin Transport
• Cholestasis
Wilson’s disease
Elevated ferritin Elevated ferritin levelslevels
• Liver dysfunction, either acute or chronic, of whatever origin (but particularly alcoholic) can lead to an increase in ferritin level.
• Other etiologies of increased ferritin levels include• Genetic hemochromatosis • Secondary iron-overload conditions (hemolysis,
transfusions) • Some cases of steatosis (Moirand et al., 1997) • Hepatocellular carcinoma • Infection • Leukemia, lymphoma, breast or lung cancer • Hyperthyroidism • Still's disease • Gaucher's disease
Hepatic iron index
Skin disorder and elevated liver enzymes
elevated
Do you know diseases leading to both elevated aminotransferases
and skin disorders?
• Hemochromatosis
• Cirrhosis
• Acute viral hepatitis
• Primary biliary cirrhosis (PBC)
• Other diseases
Do you know diseases leading to both elevated aminotransferases
and skin disorders?
• Hemochromatosis
• Cirrhosis
• Acute viral hepatitis
• Primary biliary cirrhosis (PBC)
• Other diseases
Differential diagnosis of abnormal liver Differential diagnosis of abnormal liver tests and skintests and skin
• Viral hepatitis A, B and C• vasculitis-like lesions can occur due to deposition in the skin of immune
complexes
• Viral hepatitis A• a transient maculo-papular or urticarial rash can occur
• Chronic hepatitis B• Polyarteritis nodosa with vasculitis, and in younger children in papular
acrodermatitis (Gianotti-Crosti syndrome) with papular eruptions on the face and extremities
• Chronic hepatitis C• Mixed cryoglobulinemia, polyarteritis nodosa, erythema nodosum and
lichen planus
• Porphyria cutanea tarda (elicited by or combined) with HCV • Alcohol abuse
• Psoriasis and can lead to nummular eczema (discoid plaques on the lower limbs)
• Sarcoidosis (rare)
Elevated liver enzymes• Acute elevation of transaminasesAcute elevation of transaminases• Chronic elevation of transaminasesChronic elevation of transaminases
in:in:• A patient taking a drug• Obese patient / Suspected alcoholism• Celiac disease
• Metabolic diseases
• CholestasisCholestasis• Bilirubin Transport
Anicteric cholestasis can be a manifestation of several diseasesAnicteric cholestasis can be a manifestation of several diseases
Which of the following diseases do Which of the following diseases do not cause not cause
anicteric cholestasis?anicteric cholestasis?
A. AIDSB. Primary biliary cirrhosis (PBC) and primary
sclerosing cholangitis (PSC)C. Arteritis temporalisD. Complete obstruction of the common bile ductE. EndocarditisF. Gilbert's syndromeG. AmyloidosisH. Renal tumor without liver metastasis
Alkaline phosphatase can be elevated in several
diseasesA. Osteomalacia B. Late pregnancy C. Liver abscess D. Celiac diseaseE. Hyperthyroidism F. Crigler-Najjar syndromeG. Milk-alkali syndrome (Burnett's) H. Scurvy I. Lung cancer without liver metastasis
Which cause for a near-normal gammaGT can be excluded when aminotransferases are elevated
•Alcohol abuse
•Cholestasis
•Drug hepatitis
Which cause for a near-normal gammaGT can be excluded when aminotransferases are elevated
• Alcohol abuse• Chronic alcohol abuse leads to greatly enhanced
serum gammaGT
• Cholestasis • Cholestasis leads to greatly enhanced serum
gammaGT. Serum alkaline phosphatases are also enhanced in cholestasis
• Drug hepatitis• Hepatitis (viral or toxic) leads to a moderate elevation
of gammaGT, but estrogens (oral contraceptives or pregnancy) hamper the synthesis of gammaGT
Elevated liver enzymes (2)
• TransportTransport• Bilirubin
• Synthetic functionSynthetic function• Albumin, INR, cholesterol, glucose
• Fibro-markerFibro-marker• Stage of fibrosis• Fibrodynamics
Jaundice
54
CASE 1
The yellow patient
54
Case 1
• 6 year old girl
• 2 weeks fatigue
• Jaundice
• ALT 1200iu (n=30)
• AST 850 iu (n=30)
• Bilirubin 72 mmol/L (n=18)
What does “elevated bilirubin levels” mean?
Bilirubin: A breakdown of the porphyrin ring of heme containing proteins
Found in blood in 2 fractions:
• Conjugated = direct bilirubin• Unconjugated = indirect bilirubin
•Total bilirubin = direct + indirect
5757
Formation of bilirubin
• The formation of bilirubin occurs in reticuloedothelial cells in the liver and spleen.
• To be transported in blood bilirubin must be solubilized.
• Unconjugated bilirubin bound to albumin is transported to the liver.
• It is taken by hepatocytes via a carrier mediated membrane transport.
5858
5959
When do we see jaundice?
• Bilirubin above 3 mg/dl is seen as scleral icterus
6060
How much?
• 80% of 300 mg of bilirubin produced every day is derived from breakdown of hemoglobin in old red blood cells.
• The reminder comes from prematurely destroyed erythroid cells in the bone marrow and from turnover of hemoproteins such as myoglobin and cytochromes in body tissues.
6161
In the hepatocyte
• Bilirubin enters the endoplasmic reticulum and is conjugated to glucoronic acid.
• Conjugated bilirubin diffuse from the ER to the canalicular membrane where it is actively trasnported into canalicular bile by an energy dependent mechanism involveing MDR protein 2.
6262
6363
In the intestine
• Conjugated bilirubin is not taken by the intestine cells.
• In the distal ileum it is hydrolyzed to unconjugated bilirubin by bacteria.
• Unconjugated bilirubin is reduced by the normal gut flora to form a group of colorless tetrahdyroles called urobilinogens.
• 90% of the urobilinogen is secreted in the feces.• 10% of the urobilinogen is passively absorbed to the
protal blood and re-excreted by the liver.• A small fraction of uroblinogen escapes hepatic uptake
and filters across renal glomeruli to urine.
64
CASE 2
The yellow patient
64
6565
Conjugated = directWater soluble & excreted by the kidneyNormal in serum: 30% direct
Unconjugated = indirectInsoluble in water & bound to albumin in blood
Van Den Bergh assay: measure conjugated bilirubinAfter addition of alcohol, total amount is measuredThe indirect is the difference
6666
Elevation of unconjugated bilirubin (<15%)
• Rarely due to liver disease• Hemolysis• Congenital: Crigler Najjar syndrome; Gilbert syndrome
6767
Elevation of conjugated bilirubin (>15%)
• Liver or biliary tract disease
• Intrahepatic: hepatitis, acute and chronic liver disease, toxins
• Obstruction: intrahepatic, extrahepatic
• Inherited: Dubin Johnson, Rotor
6868
Urine bilirubin
Unconjugated bilirubin always binds to albumin & is not filtered in the kidney All bilirubin in the urine is conjugated Presence of bilirubinuria implies liver disease Normal: no bilirubin in urine During prolonged cholestasis a small fraction of bilirubin from plasma is filtered by glomeruli
69
Differential diagnosis of jaundice
• Pure hypebilirubinemia
• Hepatocellular
• Cholestatic • Intrahepatic cholestasis
• Extrahepatic cholestasis
7070
Only bilirubin elevated
DIRECT INDIRECT
Dubin-Johnson Rotor
Hemolysis evaluation
- +
GILBERT HEMOLYSIS
71
Causes of isolated hyperbilirubinemia
Direct hyperbilirubinemia
• Inherited conditions• Dubin-Johnson syndrome• Rotor's syndrome
72
Causes of isolated hyperbilirubinemia
Indirect hyperbilirubinemiaA.Hemolytic disordersInherited: Spherocytosis; elliptocytosis; Glucose-6-
phosphate dehydrogenase and pyruvate kinase; sickle cell anemia
Acquired: Microangiopathic hemolytic anemias; Paroxysmal nocturnal hemoglobinuria; Spur cell anemia; Immune hemolysis
B. Ineffective erythropoiesis: Cobalamin, folate, thalassemia, and severe iron deficiencies
C. Drugs: Rifampicin, probenecid, ribavirin
D. Inherited conditions: Crigler-Najjar types I and II; Gilbert's syndrome
73
Differential diagnosis of jaundice
• Pure hypebilirubinemia
• Hepatocellular
• Cholestatic • Intrahepatic cholestasis
• Extrahepatic cholestasis
74
Hepatocellular conditions that may produce Jaundice
• Viral hepatitisHepatitis A, B, C, D and EEpstein-Barr virusCytomegalovirusHerpes simplex
• Alcohol• Drug Toxicity• Enviromental toxins
Vinyl chlorideWild mushrooms – Amanita phalloides or A. verna
• Wilson's disease• Autoimmune hepatitis
7676
Case 3:• 78 years old male• Jaundice for 6 weeks• Lost 7 kg last month
GGT 1000 iu (normal up to 80)ALP 2000 iu (normal up to 130)Bilirubin 85 mmol/liter (normal up to 17)AST 75 (normal up to 40)ALT 65 (normal up to 40)INR 1.0
Cholestatic pattern
77
Differential diagnosis of jaundice
• Pure hypebilirubinemia
• Hepatocellular
• Cholestatic • Intrahepatic cholestasis
• Extrahepatic cholestasis
78
Extrahepatic cholestatic conditions that may produce Jaundice
• Malignant• Cholangiocarcinoma• Pancreatic cancer• Gallbladder cancer• Ampullary cancer• Malignant involvement of the porta hepatic lymph
nodes
• Benign• Choledocholithiasis• Postoperative biliary structures• Primary sclerosing cholangitis• Chronic pancreatitis• AIDS Cholangiopathy• Mirizzi syndrome• Parasitic disease (ascariasis)
79
Intrahepatic cholestatic conditions that may produce Jaundice
Viral hepatitisFibrosing cholestatic hepatitis – hepatitis B and CHepatitis A, Epstein-Barr virus, cytomegalovirus
Alcoholic hepatitisDrug toxicityPrimary biliary cirrhosisPrimary sclerosing cholangitisVanishing bile duct syndrome: Chronic rejection; Sarcoidosis; DrugsInherited: Progressive familial intrahepatic cholestasis; Benign recurrent
cholestasisCholestasis of pregnancyTotal parenteral nutritionNonhepatobiliary sepsisBenign postoperative cholestasisParaneoplastic syndromeVenooclusive diseaseGraft-verus-host diaseaseInfiltrative disease: TB; Lymphoma; Amyloid
8080
Cholestatic pattern
Review drugs
Ultrasound
Intrahepatic Extrahepatic
Non-dilated ducts Dilated ducts
ERCP / MRCP / CT/ EUS
AMA - AMA +
Liver biopsyERCP
Liver biopsy
Case 2:GGT 1000 iu (normal up to 80)ALP 2000 iu (normal up to 130)Bilirubin 85 mmol/liter AST 75 (normal up to 40)ALT 65 (normal up to 40)INR 1.0
Cholestatic pattern
8282
Case 3:• 65 years old male• Jaundice for 6 weeks
GGT 1000 iu (normal up to 80)ALP 2000 iu (normal up to 130)AST 75 (normal up to 40)ALT 65 (normal up to 40)INR 1.0
Cholangiocarcinoma
Conjugated hyperbilirubinemia
DubinJohnson
Rotor’ssyndrome
Dark pigmentationof the liver
Normalpigmentation
Defect Impaired biliarycanalicilartransport of organicanions (conjugatedbilirubin) – effluxinto circulation
Defects in hepaticuptake and storageof bilirubin andrelated cholephylicorganic anions
Signs Asymptomaticjaundice
Asymptomaticjaundice
Bilirubin 2-5 mg/dL – 60%conjugated
2-5 mg/dL – 60%conjugated
Non-conjugated hyperbilirubinemia
CriglerNaiiarType 1
CriglerNaiiarType 2
Gilbert’ssyndrome
BilirubinUGT-activityIn heaptic cell
Undectable Severlydecreased but
detectable
Reduced by30%
Uncojugatedbilirubin
10-40 mg/dL 7-15 mg/dL 1-5 mg/dL
Phenobarbitalaction
No effect Reducesbilirubin with
more 20 %
Jaundicedisappears
Prognosis Kericterusdeath
Rarelykernicterus
Excellent
Elevated liver enzymes (2)
• TransportTransport• Bilirubin
• Synthetic functionSynthetic function• Albumin, INR, cholesterol, glucose
• Fibro-markerFibro-marker• Stage of fibrosis• Fibrodynamics
Features of an Ideal Marker of Liver FibrosisFeatures of an Ideal Marker of Liver Fibrosis
• Liver specificLiver specific
• Stage of fibrosisStage of fibrosis
• Activity of matrix depositionActivity of matrix deposition
• Easy to performEasy to perform
StudyStudy Serological Test Serological Test Disease Disease Correlation with Correlation with Fibrosis Fibrosis
SensitivitySensitivity Specificity
McCormick (146) ALT HCV 0.35
Assy (72) HCV 0.51Wong (74) HCV 76 48
Imperiale (61) AST/ALT ratio HCV 56 90
Giannini (64) HCV 77.8 96.9
Pohl (89) HCV 56 90Park (63) HCV 0.19 47 97Angulo (76) NAFLD 0.182
Sheth (62) 53 100 Giannini (64) Platelets HCV 91.1 88.3
Beaton (147) Hemochromatosis 79 82
Giannini (64) AST/ALT ratio + platelet count HCV 96.7 86.4
Pohl (89) HCV 41 99Bonacini (148) Discriminant* score Mixed 0.64 46 96
Saadeh (149) HCV 32 96
Croquet (65) Prothrombin index Mixed 0.70
Teare (69) PGA Mixed 91 81
Naveau (68) PGAA index Alcohol 79 89
Imbert-Bismut (71) Fibrotest HCV 75 85
Rossi (150) HCV 67 78
Forns (86) Forns fibrosis index HCV 94 51
Wai (88) APRI HCV 89 75
• Age (y)
• Male gender n, (%)
• AST (IU/L)
• ALT (IU/L)
• Gamma-GT (IU/L)
• Bilirubin (mg/dL)
• Glucose (mg/dL)
• Cholesterol (mg/dL)
• Albumin (g/L)
• Leucocytes (109/L)
• Platelets (109/L)
• Prothrombin time (%)
• Viral load (IU/mL X103)
• HCV Genotype 1
Identification of Chronic Hepatitis C Patients Identification of Chronic Hepatitis C Patients
Without Hepatic Fibrosis by a Without Hepatic Fibrosis by a Simple Simple Predictive ModelPredictive Model
Xavier Forns,et alXavier Forns,et al, , Hepatology. 2002 Oct;36(4 Pt 1):986-92Hepatology. 2002 Oct;36(4 Pt 1):986-92. .
• AST
• 2 macroglobulin
• ALT
• Haptoglobin (decrease)
• globulin
• GGT
• Total bilirubin
• Apo A1 (decrease)
• Albumin (decrease)
1 globulin
2 globulin (decrease)
• globulin
Biochemical markers of liver fibrosis in patients withBiochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective studyhepatitis C virus infection: a prospective study
Vlad Ratziu, Laurence Pieroni, Frederic Charlotte, Yves Benhamou, Thierry Poynard, for Vlad Ratziu, Laurence Pieroni, Frederic Charlotte, Yves Benhamou, Thierry Poynard, for thethe
MULTIVIRC group, MULTIVIRC group, THE LANCET • Vol 357 • April 7, 2001THE LANCET • Vol 357 • April 7, 2001
Markers of matrix depositionMarkers of matrix deposition Procollagen I C terminal
Procollagen III N terminal
Tenascin
Tissue inhibitor of metalloproteinase TIMP
TGF
Markers of matrix removalMarkers of matrix removal Procollagen IV C peptide
Procollagen IV N peptide (7-S collagen)
Collagen IV
Undulin
Metalloproteinase MMP
Urinary desmosine and hydroxylysylpyridinoline
UncertainUncertain Hyaluronan
Laminin
YKL-40 (Chondrex)
?האם הביופסיה מייצגת? הומוגנית
Sampling Variability of Liver Biopsy in NAFLD
האם ביופסית הכבד חשובה ?לאבחנת המחלה
סמך על :האבחנה
ההפטיטיס לוירוס חיוביים בדם C נוגדניםAnti HCV Ab’s
עםהנגיף לנוכחות מולקולרית עדותHCVPCR positive
?מהם חסרונות הביופסיה
• במהלך פעמיים או פעם מבוצע ולכן חודרניהשנים
• Inter/intra-observer variability
• רק מהכבד 1:50000דוגם• 3:10000תמותה • 1:1000תחלואה
• אחוז 30כאב • " - ב וכי קרישה נגד התוויות קיימות
• 2000$מחיר-
האם קיימות אלטרנטיבות לביופסית הכבד? ?מה דרוש מהאלטרנטיבה
• - האלטרנטיבה סטטי מצב דוגמת ביופסיהדינמיקה לייצג אמורה
לכבד • ספציפית
ומינימליים • עדינים שנויים מייצגת
•Reproducible
Staging Systems• Ordinal categorical variables
• Categories are not evenly distributed
• Ordinal categorical variables
• Categories are not evenly distributed
-4
-3
-2
-1
0
1
2
3
4
5
6
0 1 2 3 4
Scheuer Fibros is Score
Dis
crim
inan
t S
core
MildModerate
severe
• Blood tests
– Fibrotest
– APRI
– ELF
– Forn’s
– FIBROSpect
– Fibrometer
– Hepascore
– FIB-4 (coinfected patients)
• Blood tests
– Fibrotest
– APRI
– ELF
– Forn’s
– FIBROSpect
– Fibrometer
– Hepascore
– FIB-4 (coinfected patients)
Non-Invasive: Test of Fibrosis
• Liver Imaging
–Transient
elastrography
–MR spectoscopy
–Diffuse-
weighted MRISterling, Hepatology. 2006 43(6):1317-25Halfon Am J Gastro. 2006; 101: 547-55Wai Hepatol. 2003; 38: 518-26Forms, Hepatol. 2002; 36:986-92Patel, J Hepatol. 2004; 41: 935-42
Rosenberg, Gastro 2004 127:1704-13Zaman, Am J Gastro. 2007; 120: e9-12Lewin, Hepatol. 2007; 46: 658-65Adams, Clin Chem. 2005; 51:1867-167Cales, J Hepatol. 20054; 42: 1373-1383
Fibroscan-LimitationsFibroscan-Limitations
-Ascites-Ascites -Obese patients*-Obese patients*
-Narrow intercostal space*-Narrow intercostal space*
*need a special probe.*need a special probe.
FibroTestFibroTest ActiTest ActiTest• Serologic markers based algorithmSerologic markers based algorithm
• Assess the degree of fibrosis and Assess the degree of fibrosis and necroinflammatory histological activitynecroinflammatory histological activity
• Combined 5 componentsCombined 5 components
FibroTestFibroTest ActiTest ActiTest
0.00
0.33
0.67
1.00
F0 F1 F2 F3 F4
Fib
rote
st
FibroFibroTest: Test: from blood donors to from blood donors to cirrhotics (n=1570) Clin Chem 2004, cirrhotics (n=1570) Clin Chem 2004,
Comp Hepatol 2004Comp Hepatol 2004
FibroTestFibroTest ActiTest ActiTest LimitationsLimitationsImpact of inflammation and therapyImpact of inflammation and therapy - inaccurate in patients receiving - inaccurate in patients receiving
anti-viral therapy .anti-viral therapy . - sensitive to haemolysis (Ribavirin). - sensitive to haemolysis (Ribavirin). Impact of co-morbidityImpact of co-morbidity - Gilbert Syndrome.- Gilbert Syndrome. -arthritis, connective tissue -arthritis, connective tissue
diseases-not proveddiseases-not proved.
לסכום
הכבד • ממחלות גדול חלק בין משותף מכנה קיים , המעבדה ובדיקות הבדיקה הקליניקה מבחינת
לתפקודי • הכבד אנזימי בין ההבדל את להבין ישהכבד
בדם • בילירובין רמת לעלית הסיבות את להבין יש
כתחליף • חודרניות הבלתי בבדיקות הינו העתידהכבד לביופסית