Liver Diseases Prof Asaad Abdullah Assiri Professor of
Liver Diseases Prof. Asaad Abdullah Assiri Professor of Pediatrics Pediatric Gastroenterologist Department of Pediatrics College of Medicine King 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 3
BILIARY ATRESIA (continuation) § INCIDENCE 1: 15, 000 LIVE BIRTHS § CLINICALLY § § - WELL - JAUNDICE 2 WEEKS LABORATORY INVESTIGATION: 99 M 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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BILIARY ATRESIA (continuation) TREATMENT: § SURGERY § BEFORE 6 WEEKS OF AGE § KASAI OPERATION HEPATO PORTOENTEROSTOMY § LIVER TRANSPLANTATION § FAT SOLUBLE VIT. A, D, E, K § MCT 7
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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 9
NEONATAL HEPATITIS INFECTIOUS IDIOPATHIC GIANT CELL § PRENATAL TORCHS § POSTNATAL CMV, ECHOVIRUS § TYPE II, GRAM NEGATIVE § SEPTICAEMIA 10
CLINICAL PRESENTATION § SGA § PURPURA § HEPATOSPLENOMEGALY § CATARACT § THROMBOCYTOPENIA § LIVER BIOPSY MARKED INFILTRATE OF INFLAMMATORY CELLS FOCAL HEPATOCELLULAR NECROSIS, GIANT CELLS 11
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CONJUGATED NONCHOLESTATIC 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 14
CONJUGATED HYPERBILIRUBINAEMIA (CH) DIRECT = (DH) § IT IS ALWAYS PATHOLOGICAL § CLINICALLY - PALE - DARK URINE - PRURITIS 15
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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 * a 1 ANTITRYPSIN DEFICIENCY * CEREBRO HEPATORENAL SYNDROME (ZELLWEGER SYNDROME) * RECURRENT FAMILIAL CHOLESTASIS (BYLER DISEASE) * TOTAL PARENTAL NUTRITION 20
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 a 1 -ANTITRYPSIN 21
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 XRAY FILMS ABDOMINAL ULTRASOUND DUODENAL INTUBATION (STRING TEST FOR COLOR, BILIRUBIN, BILE ACIDS) HEPATOBILIARY SCINTIGRAPHY PERCUTANEOUS LIVER BIOPSY 22
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ACUTE VIRAL 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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VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF SEROLOGICAL MARKERS OF VIRAL HEPATITIS MARKER SIGNIFICANCE § HEPATITIS A: ACUTE HEPATITIS Igm HAV Ab § Ig. G HAV Ab (MAY BE POSITIVE FOR UP TO ONE YEAR) IMMUNITY TO HEPATITIS A DUE TO PAST INFECTION, ACTIVE IMMUNIZATION OR PASSIVE IMUNIZATION 26
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 27
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VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation) MARKER § HEPATITIS B: HBs. Ag § Igm HBc. Ab § Ig. G HBc. Ab SIGNIFICANCE ACUTE OR CHRONIC HEPATITIS B INFECTION HIGH TITRE: ACUTE HEPATITIS LOW TITRE: CHRONIC INFECTION PAST EXPOSURE TO HEPATITIS B OR 29
VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation) MARKE SIGNIFICANCE R § HBs. Ab § HBe. Ag § HBe. Ab IMMUNITY TO HEPATITIS B, POST-INFECTIVE OR WITH ACTIVE OR PASSIVE IMMUNIZATION HIGHLY INFECTIOUS STATE IN ACUTE OR CHRONIC INFECTION LESS INFECTIVE STATE IN THE 30
VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation) MARKER SIGNIFICANCE § HBV-SPECIFIC A MORE SENSITIVE DNA POLYMERASE § HBV DNA BY DIRECT DNA HYBRIDIZATION § DANE PARTICLE INDICATOR OF PERSISTING VIRAL INFECTION AN EVEN MORE SENSITIVE INDICATOR OF VIRAL REPLICATION HIGHLY INFECTIOUS STATE IN ACUTE OR CHRONIC 31
VIRAL INFECTION OF THE LIVER SIGNIFICANCE OF SEROLOGICAL MARKERS OF VIRAL HEPATITIS (continuation) MARKER § DANE ANTIBODY § DELTA AGENT § Ig. M DELTA ANTIBODY § Ig. G DELTA ANTIBODY SIGNIFICANCE PAST INFECTION ACUTE OR CHRONIC INFECTION WITH DELTA CONTINUING DELTA INFECTION PAST DELTA INFECTION 32
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 35
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CHRONIC PERSISTANT HEPATITIS § HISTOLOGY: - MONONUCLEAR CELL INFILTRATION - NO ENCROACHMENT INTO THE PERIPORTAL AREA § CLINICAL: - ASYMPTOMATIC - (INC. ) LIVER ENZYME § PROGNOSIS GOOD 37 37
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CHRONIC ACTIVE HEPATITIS (CAH) §PATHOLOGY: MONONUCLEAR AND PLASMA CELL INFILTRATION OF THE PORTAL AND PERIPORTAL AREAS OF THE LIVER AND DESTRUCTION OF THE HEPATOCYTES. 39
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 – B 8, HLADW 3 § PX: - STEROID - AZATHIOPRINE 41
HBV-INDUCED CHRONIC ACTIVE HEPATITIS § CHRONIC LIVER DISEASE § HEPATO-CELLULAR CARCINOMA § PX: - INTERFERONE - VIDARABINE - IMMUNO-SUPPRESSION 42
METABOLIC LIVER DISEASE §HYPOGLYCAEMIA §SPLENOMEGALY §JAUNDICE §LIVER CIRRHOSIS §HEPATITIS 43
α 1 -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 45
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 46
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 DISEASE § AUTOSOMAL RECESSIVE § MANIFESTATIONS OF WILSON’S DISEASE § HEPATIC - 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 49
LIVER CIRRHOSIS § WIDESPREAD HEPATIC FIBROSIS § CLINICAL: - FAILURE TO THRIVE - HEPATOSPLENOMEGALY - 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 51
PORTAL HYPERTENSION § UNCOMMON IN CHILDREN § CAUSES: § PRESINUSOIDAL - IDIOPATHIC - NEONATAL SEPSIS - UMBILICAL VEIN CATHERIZATION § CLINICAL: - HEMATEMESIS - SPLENOMEGALY 52
§ INTRAHEPATIC CIRRHOSIS § SUPRAHEPATIC - BUDD CHIARI SYNDROME (HEPATIC VEIN THROMBOSIS) - JAMAICAN VENO-OCCLUSIVE DISEASE 53
MANAGEMENT § Px BLEEDING § I. V. VASOPRESSIN § SCLEROTHERAPY § SURGERY 54
HEPATIC FAILURE § AETIOLOGY - 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 58
LABORATORY FINDINGS § (INC) LIVER ENZYME § (INC) BLOOD AMONIN § (DEC) Na+ (DEC) K+ (INC) UREA § HYPOGLYCAEMIA § METABOLIC ALKALOSIS § RESPIRATORY ALKALOSIS 59
§ Px - SUPPORTIVE - Px CEREBRAL OEDEMA 60
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- Slides: 62