Liver diseases

1. Prof. Asaad Abdullah Assiri
Professor of Pediatrics
Pediatric Gastroenterologist
Department of Pediatrics
College of Medicine
King Saud University

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3. 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

4. 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 4

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7. BILIARY ATRESIA
(continuation)
TREATMENT:
▪ SURGERY
▪ BEFORE 6 WEEKS OF AGE
▪ KASAI OPERATION HEPATO PORTOENTEROSTOMY
▪ LIVER TRANSPLANTATION
▪ FAT SOLUBLE VIT. A, D, E, K
▪ MCT
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9. 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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10. NEONATAL HEPATITIS
INFECTIOUS GIANT CELL IDIOPATHIC
▪ PRENATAL TORCHS
▪ POSTNATAL CMV, ECHOVIRUS
▪ TYPE II, GRAM NEGATIVE
▪ SEPTICAEMIA
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11. CLINICAL PRESENTATION
▪ SGA
▪ PURPURA
▪ HEPATOSPLENOMEGALY
▪ CATARACT
▪ THROMBOCYTOPENIA
▪ LIVER BIOPSY MARKED INFILTRATE OF
INFLAMMATORY CELLS FOCAL HEPATOCELLULAR
NECROSIS, GIANT CELLS 11

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14. 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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15. CONJUGATED
HYPERBILIRUBINAEMIA (CH)
DIRECT = (DH)
▪IT IS ALWAYS PATHOLOGICAL
▪CLINICALLY
- PALE
- DARK URINE
- PRURITIS
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18. D.D. DIAGNOSIS OF
CONJUGATED
HYPERBILIRUBINAEMIA
▪EXTRA HEPATIC BILE DUCT
OBSTRUCTION
- BILIARY ATRESIA
- CHOLEDOCHAL CYST
- SPONTANEOUS RUPTURE OF BILE DUCT
- INSPISSATED BILE SYNDROME
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19. D.D. DIAGNOSIS OF
CONJUGATED
HYPERBILIRUBINAEMIA
▪INTRA-HEPATIC CHOLESTASIS WITH
PAUCITY OF BILE DUCT
- ALAGILE SYNDROME
- NON-SYNDROMATIC PAUCITY OF INTRA-
HEPATIC
DUCTS
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20. 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 NUTRITION
20

21. 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. 21

22. 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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24. 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
CONTACT 24

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26. 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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27. ACUTE VIRAL HEPATITIS
▪HEPATITIS B:
- I. P. 150-180 DAYS
▪SOURCES OF INFECTION:
- BLOOD TRANSFUSION
- DIRECT CONTACT WITH CASES
▪VIRUS AND VIRUS MARKER
▪CLINICAL PRESENTATION
▪MANAGEMENT
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29. 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 HEPATITIS
LOW TITRE: CHRONIC INFECTION
▪ IgG HBcAb PAST EXPOSURE TO HEPATITIS B OR
CONTINUING HEPATITIS B INFECTION
(IF HBsAb IS POSITIVE)
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30. 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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31. 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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32. 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 INFECTION
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33. ACUTE VIRAL HEPATITIS
▪HEPATITIS D: (DELTA VIRUS)
- HEPATITIS
- FULMINANT HEPATIC FAILURE
- LIVER CIRRHOSIS
- HEPATO-CELLULAR CARCINOMA
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34. ACUTE VIRAL HEPATITIS
▪HEPATITIS C:
- CHRONIC LIVER DISEASES
- LIVER CIRRHOSIS
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35. ACUTE VIRAL HEPATITIS
▪HEPATITIS E:
- WATER BORNE EPIDEMIC OF HEPATITIS
- MILD ILLNESS
- NO CHRONOCITY ?
- MAYBE FULMINANT HEPATITIS
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CHRONIC PERSISTANT
HEPATITIS
▪HISTOLOGY:
- MONONUCLEAR CELL INFILTRATION
- NO ENCROACHMENT INTO THE PERIPORTAL
AREA
▪CLINICAL:
- ASYMPTOMATIC
- (INC.) LIVER ENZYME
▪PROGNOSIS GOOD
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39. 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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40. AUTOIMMUNE CAH
▪ CLINICAL
- FEMALE
- 10-25 YEARS OLD
- JAUNDICE
- CHRONIC LIVER DISEASE
- AUTO-IMMUNE HAEMOLYTIC
ANAEMIA
- AUTO-IMMUNE THYROIDITIS
- LEUCOPENIA, ANAEMIA
40

41. INVESTIGATION
▪ AUTO ANTIBODIES
▪ (INC) LIVER ENZYME
▪ HLA – B8, HLADW3
▪ PX:
- STEROID
- AZATHIOPRINE
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42. HBV-INDUCED CHRONIC
ACTIVE HEPATITIS
▪ CHRONIC LIVER DISEASE
▪ HEPATO-CELLULAR CARCINOMA
▪ PX:
- INTERFERONE
- VIDARABINE
- IMMUNO-SUPPRESSION
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43. METABOLIC LIVER
DISEASE
▪HYPOGLYCAEMIA
▪SPLENOMEGALY
▪JAUNDICE
▪LIVER CIRRHOSIS
▪HEPATITIS
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44. 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
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45. 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
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46. TYPE 1
▪GLUCOSE -6- PHOSPHATASE DEFICIENCY
▪HYPOGLYCAEMIA
▪HEPATOMEGALY
▪METABOLIC ACIDOSIS
▪HYPERLIPIDAEMIA
▪LABORATORY:
- (DEC) RESPONSE OF BLOOD SUGAR TO GLUCAGON
- LIVER BIOPSY HISTOLOGY, ENZYME ASSAY
▪Px HIGH STARCH DIET
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47. 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
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48. WILSON DISEASE
▪AUTOSOMAL RECESSIVE
▪MANIFESTATIONS OF WILSON’S DISEASE
▪HEPATIC
- HEPATOMEGALY
- HEPATOSPLENOMEGALY
- JAUNDICE
- CHRONIC AGGRESSIVE HEPATITIS
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49. ▪ 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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50. 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
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51. ▪ INVESTIGATION:
- ABDOMINAL U/S
- ABDOMINAL CT SCAN
- LIVER BIOPSY
▪ Px THE CAUSE
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52. PORTAL HYPERTENSION
▪UNCOMMON IN CHILDREN
▪CAUSES:
▪ PRESINUSOIDAL
- IDIOPATHIC
- NEONATAL SEPSIS
- UMBILICAL VEIN CATHERIZATION
▪ CLINICAL:
- HEMATEMESIS
- SPLENOMEGALY
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53. ▪INTRAHEPATIC CIRRHOSIS
▪SUPRAHEPATIC
- BUDD CHIARI SYNDROME (HEPATIC VEIN
THROMBOSIS)
- JAMAICAN VENO-OCCLUSIVE DISEASE
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54. MANAGEMENT
▪Px BLEEDING
▪I. V. VASOPRESSIN
▪SCLEROTHERAPY
▪SURGERY
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55. HEPATIC FAILURE
▪AETIOLOGY
- VIRAL HEPATITIS A, B, C, E
- PARACETAMOL
INH, COTRIMOXAZOLE
Na VALPORATE, PHENYTOIN
- REYE’S SYNDROME
- WILSON DISEASE
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56. HEPATIC FAILURE
(continuation)
▪CLINICAL
- DROWSINESS
- CONFUSION
- FLAPPING TREMOR
- COMA
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57. ▪ Px
- CIMITIDINE
- RESPIRATORY SUPPORT
- HEMODIALYSIS
- Px CEREBRAL OEDEMA
- Px ENCEPHALOPATHY
- ORAL LACTULOSE
NEOMYCIN, METRONIDAZOLE
- PROTEIN RESTRICTION
- FFP, VIT K
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58. REYE’S SYNDROME
▪ ENCEPHALOPATHY
▪ FATTY DEGENERATION OF THE LIVER
▪ CLINICAL
- FLU LIKE ILLNESS
- APPARENT IMPROVEMENT VOMITING
- DETERIORATING CONSCIOUSNESS COMA
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59. LABORATORY FINDINGS
▪(INC) LIVER ENZYME
▪(INC) BLOOD AMONIN
▪(DEC) Na+ (DEC) K+ (INC) UREA
▪HYPOGLYCAEMIA
▪METABOLIC ALKALOSIS
▪RESPIRATORY ALKALOSIS
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60. ▪ Px
- SUPPORTIVE
- Px CEREBRAL OEDEMA
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