Prof. Asaad Abdullah AssiriProfessor of Pediatrics

Pediatric GastroenterologistDepartment of Pediatrics

College of MedicineKing Saud University

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BILIARY ATRESIA ETIOLOGY / PATHOLOGY PROGRESSIVE PANDUCTULARSCLEROTIC

PROCESS THAT MAY CONTINUE IN THE INTRAHEPATIC DUCT EVEN AFTER SURGICAL RELIEF OF BILIARY OBSTRUCTION

INTRA-UTERINE REOVIRUS TYPE III INFECTION 10%-15% INCIDENCE OF ASSOCIATED

ANOMALIES- PRE-DUODENAL PORTAL VIEW- INTESTINAL MALROTATION- POLYSPLENIA- ABSENT INFERIOR VENA CAVA

3

BILIARY ATRESIA (continuation)

INCIDENCE 1:15,000 LIVE BIRTHS CLINICALLY

- WELL- JAUNDICE 2 WEEKS

LABORATORY INVESTIGATION: 99M TC IMINODIACETIC ACID (IDA SCAN)

- SLOW UPTAKE WITH NO OR DELAYED EXCRETION (PARENCHYMAL DYSFUNCTION)- RAPID HEPATOCYTE UPTAKE WITH NO INTESTINAL EXCRETION (EXTRA HEPATIC OBSTRUCTION)

ABDOMINAL ULTRASOUND LIVER BIOPSY OPERATIVE CHOLANGIOGRAPHY 4

5

6

BILIARY ATRESIA (continuation)

TREATMENT: SURGERY

BEFORE 6 WEEKS OF AGE

KASAI OPERATION HEPATO PORTOENTEROSTOMY

LIVER TRANSPLANTATION

FAT SOLUBLE VIT. A, D, E, K

MCT7

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BILIARY ATRESIA (continuation)

PROGNOSIS OF KASAI OPERATION

10% NO BILE DRAINAGE

90% BILE DRAINAGE

- 1/3 FAIL SEVERE LIVER DAMAGE

- 1/3 INDETERMINATE – MODERATE LIVER

DISEASE

- 1/3 CURED – MINIMAL LIVER DISEASE

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NEONATAL HEPATITIS

INFECTIOUS GIANT CELLIDIOPATHIC

PRENATAL TORCHS POSTNATAL CMV, ECHOVIRUS TYPE II, GRAM NEGATIVE SEPTICAEMIA

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CLINICAL PRESENTATION

SGA

PURPURA

HEPATOSPLENOMEGALY

CATARACT

THROMBOCYTOPENIA

LIVER BIOPSY MARKED INFILTRATE OF

INFLAMMATORY CELLS FOCAL

HEPATOCELLULAR NECROSIS, GIANT CELLS11

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CONJUGATED NON-CHOLESTATIC

HYPERBILIRUBINAEMIA DUBIN – JOHNSON SYNDROME ROTOR’S SYNDROME DEFECTIVE EXCRETION OF CONJUGATED

BILIRUBIN FROM HEPATOCYTE NORMAL HANDLING OF BILE ACID NORMAL LFTA MILD CONJUGATED HYPERBILIRUBINAEMIA LIVER BIOPSY

- NORMAL IN ROTORS- PIGMENTED GRANULE IN DUBBIN-JOHNSON

PROGNOSIS EXCELLENT

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CONJUGATED HYPERBILIRUBINAEMIA

(CH)DIRECT = (DH)

IT IS ALWAYS PATHOLOGICALCLINICALLY

- PALE- DARK URINE- PRURITIS

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16

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D.D. DIAGNOSIS OF CONJUGATED

HYPERBILIRUBINAEMIA EXTRA HEPATIC BILE DUCT OBSTRUCTION

- BILIARY ATRESIA

- CHOLEDOCHAL CYST

- SPONTANEOUS RUPTURE OF BILE DUCT

- INSPISSATED BILE SYNDROME 18

D.D. DIAGNOSIS OF CONJUGATED

HYPERBILIRUBINAEMIA INTRA-HEPATIC CHOLESTASIS WITH PAUCITY OF BILE DUCT- ALAGILE SYNDROME- NON-SYNDROMATIC PAUCITY OF INTRA-HEPATIC

DUCTS 19

D.D. DIAGNOSIS OF CONJUGATED

HYPERBILIRUBINAEMIA INTRA-HEPATIC CHOLESTASIS WITH

NORMAL BILE DUCT- GIANT CELL HEPATITIS- INFECTIOUS AGENTS - CMV, RUBELLA, HERPES- METABOLIC:

* GALACTOSEMIA* a1 ANTITRYPSIN DEFICIENCY* CEREBRO HEPATORENAL SYNDROME

(ZELLWEGER SYNDROME) * RECURRENT FAMILIAL CHOLESTASIS (BYLER DISEASE)

* TOTAL PARENTAL NUTRITION20

CONJUGATED HYPERBILIRUBINAEMIA

EVALUATION FRACTIONATE SERUM BILIRUBIN SERUM TRANSMINASES, ALKALINE PHOSPHATASE

(OR 5’ – NUCLEOTIDASE), ALBUMIN CHOLESTEROL PROTHROMBIN TIME

STOOL COLOR CULTURES (BLOOD, URINE, ETC.) HEPATITIS B SURFACES ANTIGEN, TORCH TITERS,

VDRL SERUM a1-ANTITRYPSIN LEVEL AND PHENOTYPE.

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CONJUGATED HYPERBILIRUBINAEMIA EVALUATION (continuation)

METABOLIC SCREEN-URINE / SERUM AMINO ACIDS; URINE FOR REDUCING SUBSTANCE

THYROID SCREEN OPHTHALMOLOGIC EXAMINATION SWEAT CHLORIDE SKULL, LONG BONES, ABDOMINAL AND CHEST X-

RAY FILMS ABDOMINAL ULTRASOUND DUODENAL INTUBATION (STRING TEST FOR

COLOR, BILIRUBIN, BILE ACIDS) HEPATOBILIARY SCINTIGRAPHY PERCUTANEOUS LIVER BIOPSY

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ACUTE VIRAL HEPATITIS

HEPATITIS A: I. P. 6 WEEKS TRANSMISSION FOETAL – ORAL ROUT NO CHRONIC CARRIER STATE LAB: Igm SPECIFIC ANTI HAV

MANAGEMENT: ISOLATION BED REST PERSONAL HYGIENE HUMAN IMMUNOGLOBULIN 0.02 ml/kg

FOR CONTACT24

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VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF SEROLOGICAL MARKERS OF VIRAL HEPATITIS

MARKER SIGNIFICANCE HEPATITIS A: Igm HAV Ab

ACUTE HEPATITIS (MAY BE POSITIVE FOR UP TO ONE YEAR)

IgG HAV Ab IMMUNITY TO HEPATITIS A DUE TO PAST INFECTION, ACTIVE IMMUNIZATION OR PASSIVE IMUNIZATION

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ACUTE VIRAL HEPATITIS

HEPATITIS B:- I. P. 150-180 DAYS

SOURCES OF INFECTION:- BLOOD TRANSFUSION

- DIRECT CONTACT WITH CASES

VIRUS AND VIRUS MARKERCLINICAL PRESENTATIONMANAGEMENT

27

28

VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF

SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation)

MARKER SIGNIFICANCE HEPATITIS B: HBsAg

ACUTE OR CHRONIC HEPATITIS B INFECTION

Igm HBcAb HIGH TITRE: ACUTE HEPATITISLOW TITRE: CHRONIC INFECTION

IgG HBcAb PAST EXPOSURE TO HEPATITIS B OR CONTINUING HEPATITIS B INFECTION (IF HBsAb IS POSITIVE)

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VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF

SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation)

MARKER

SIGNIFICANCE

HBsAb IMMUNITY TO HEPATITIS B, POST-INFECTIVE OR WITH ACTIVE OR PASSIVE IMMUNIZATION

HBeAg HIGHLY INFECTIOUS STATE IN ACUTE OR CHRONIC INFECTION

HBeAb LESS INFECTIVE STATE IN THE HBsAb POSITIVE PATIENT

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VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF

SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation)

MARKER SIGNIFICANCE HBV-SPECIFIC DNA POLYMERASE

A MORE SENSITIVE INDICATOR OF PERSISTING VIRAL INFECTION

HBV DNA BY DIRECT DNA HYBRIDIZATION

AN EVEN MORE SENSITIVE INDICATOR OF VIRAL REPLICATION

DANE PARTICLE POSITIVE

HIGHLY INFECTIOUS STATE IN ACUTE OR CHRONIC INFECTION

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VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF

SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation)

MARKER SIGNIFICANCE DANE ANTIBODY

PAST INFECTION

DELTA AGENT ACUTE OR CHRONIC INFECTION WITH DELTA

IgM DELTA ANTIBODY

CONTINUING DELTA INFECTION

IgG DELTA ANTIBODY

PAST DELTA INFECTION32

ACUTE VIRAL HEPATITIS

HEPATITIS D: (DELTA VIRUS)- HEPATITIS- FULMINANT HEPATIC FAILURE- LIVER CIRRHOSIS- HEPATO-CELLULAR CARCINOMA

33

ACUTE VIRAL HEPATITIS

HEPATITIS C:- CHRONIC LIVER DISEASES- LIVER CIRRHOSIS

34

ACUTE VIRAL HEPATITIS

HEPATITIS E:- WATER BORNE EPIDEMIC OF HEPATITIS- MILD ILLNESS- NO CHRONOCITY ?- MAYBE FULMINANT HEPATITIS

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36

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CHRONIC PERSISTANT HEPATITIS

HISTOLOGY:- MONONUCLEAR CELL INFILTRATION- NO ENCROACHMENT INTO THE PERIPORTAL AREA

CLINICAL:- ASYMPTOMATIC- (INC.) LIVER ENZYME

PROGNOSIS GOOD37

3838

CHRONIC ACTIVE HEPATITIS (CAH)

PATHOLOGY:

MONONUCLEAR AND PLASMA CELL

INFILTRATION OF THE PORTAL AND

PERIPORTAL AREAS OF THE LIVER AND

DESTRUCTION OF THE HEPATOCYTES.

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AUTOIMMUNE CAH CLINICAL

- FEMALE- 10-25 YEARS OLD- JAUNDICE- CHRONIC LIVER DISEASE- AUTO-IMMUNE HAEMOLYTIC ANAEMIA- AUTO-IMMUNE THYROIDITIS- LEUCOPENIA, ANAEMIA

40

INVESTIGATION AUTO ANTIBODIES (INC) LIVER ENZYME

HLA – B8, HLADW3 PX:

- STEROID- AZATHIOPRINE

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HBV-INDUCED CHRONIC ACTIVE

HEPATITIS CHRONIC LIVER DISEASE HEPATO-CELLULAR CARCINOMA

PX:- INTERFERONE- VIDARABINE- IMMUNO-SUPPRESSION

42

METABOLIC LIVER DISEASE

HYPOGLYCAEMIASPLENOMEGALYJAUNDICELIVER CIRRHOSISHEPATITIS

43

α1-ANTITRYPSIN DEFICIENCY

a ANTITRYPSIN A GYCO PROTEIN A POTENT INHIBITOR OF MANY PROTEOLYTIC ENZYMES

20 PHENOTYPES Pi ZZ > LIVER DISEASE CLINICAL CONJUG. HYPERBILIRUBINAEMIA HEPATOMEGALY HEPATIC FAILURE LIVER CIRRHOSIS, PORTAL HYPERTENSION

- LIVER BIOPSY PERIODIC ACID – SCHIFF – POSITIVE DIASTASE RESISTANT GRANULES IN PERIPORTAL HEPATOCYTE - BIOCH 1 ANTITRYPSIN PHENOTYPE

44

GLYCOGEN STORAGE DISEASE ACCUMULATION OF GLYCOGEN IN

THE LIVER, MUSCLES AND KIDNEY

10 VARIANTS ARE RECOGNIZED

THE DIAGNOSIS IS CONFIRMED BY

ENZYME ASSAY IN LIVER TISSUE

45

TYPE 1GLUCOSE -6- PHOSPHATASE

DEFICIENCYHYPOGLYCAEMIAHEPATOMEGALYMETABOLIC ACIDOSISHYPERLIPIDAEMIALABORATORY:

- (DEC) RESPONSE OF BLOOD SUGAR TO GLUCAGON- LIVER BIOPSY HISTOLOGY, ENZYME ASSAY

Px HIGH STARCH DIET46

GALACTOSEMIA INH: AUTOSOMAL RECESSIVE GALACTOSE -

1- PHOSPHATE URIDYL TRANSFERAN DEFICIENCY

CLINICAL- VOMITING- DIARRHOEA- HYPERBILIRUBINAEMIA- CATARACT- URINE POSITIVE FOR REDUCING SUBSTANCE- RBCS GALACTOS 1 PHOSPHATE URIDYL TRANSF (DEC)

Px GALACTOSE FREE DIET 47

WILSON DISEASEAUTOSOMAL RECESSIVEMANIFESTATIONS OF WILSON’S

DISEASEHEPATIC

- HEPATOMEGALY- HEPATOSPLENOMEGALY- JAUNDICE- CHRONIC AGGRESSIVE HEPATITIS

48

EYE- KAYSER – FLEISCHER RINGS

HAEMATOLOGY- HAEMOLYTIC ANAEMIA

CNS- BEHAVIOURAL DISTURBANCES,

LABORATORY- SERUM CAERULO PLASMIN (DEC)- URINARY COPPER (INC)- LIVER COPPER (INC)

Px PENICILLAMINE

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LIVER CIRRHOSIS WIDESPREAD HEPATIC

FIBROSIS CLINICAL:

- FAILURE TO THRIVE- HEPATOSPLENOMEGALY- SPLENOMEGALY- HEPATIC ENCEPHALOPATHY- SIGNS OF CHRONIC LIVER DISEASE- MAYBE ONLY SPLENOMEGALY- MAYBE NORMAL LABORATORY FINDING

50

INVESTIGATION:

- ABDOMINAL U/S

- ABDOMINAL CT SCAN

- LIVER BIOPSY

Px THE CAUSE

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PORTAL HYPERTENSIONUNCOMMON IN CHILDRENCAUSES:

PRESINUSOIDAL- IDIOPATHIC- NEONATAL SEPSIS- UMBILICAL VEIN CATHERIZATION CLINICAL:- HEMATEMESIS- SPLENOMEGALY

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INTRAHEPATIC CIRRHOSIS

SUPRAHEPATIC

- BUDD CHIARI SYNDROME (HEPATIC

VEIN THROMBOSIS)

- JAMAICAN VENO-OCCLUSIVE DISEASE

53

MANAGEMENTPx BLEEDING

I. V. VASOPRESSIN

SCLEROTHERAPY

SURGERY

54

HEPATIC FAILUREAETIOLOGY

- VIRAL HEPATITIS A, B, C, E- PARACETAMOL INH, COTRIMOXAZOLE Na VALPORATE, PHENYTOIN- REYE’S SYNDROME- WILSON DISEASE

55

HEPATIC FAILURE (continuation)

CLINICAL

- DROWSINESS

- CONFUSION

- FLAPPING TREMOR

- COMA

56

Px- CIMITIDINE- RESPIRATORY SUPPORT- HEMODIALYSIS- Px CEREBRAL OEDEMA- Px ENCEPHALOPATHY- ORAL LACTULOSE NEOMYCIN, METRONIDAZOLE- PROTEIN RESTRICTION- FFP, VIT K

57

REYE’S SYNDROME ENCEPHALOPATHY

FATTY DEGENERATION OF THE LIVER

CLINICAL

- FLU LIKE ILLNESS

- APPARENT IMPROVEMENT VOMITING

- DETERIORATING CONSCIOUSNESS

COMA

58

LABORATORY FINDINGS

(INC) LIVER ENZYME

(INC) BLOOD AMONIN

(DEC) Na+ (DEC) K+ (INC)

UREA

HYPOGLYCAEMIA

METABOLIC ALKALOSIS

RESPIRATORY ALKALOSIS59

Px

- SUPPORTIVE

- Px CEREBRAL OEDEMA

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