Pediatric Liver Disease1

Pediatric Liver Disease

Ajai Khanna MD., Ph.D. Director Pediatric Abdominal Transplantation Programs Rady Children’s Hospital and UCSD

FHF

Segmental Anatomy of the Liver

CAUSES OF LIVER DIESEASES

Etiological Factors ◗

Diseases related to Bile ducts • Obstructive Biliary Diseases • Cholestatic Liver diseases

Etiology ◗

Diseases related to Hepatocytes • Acute and Chronic Hepatitis • • • • •

Fulminant Hepatic Failure Viral Toxic Autoimmune Idiopathic

Pediatric Liver Disease Etiological Factors

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Diseases related to Hepatocytes • Metabolic • a-1 Antitrypsin Deficiency • Tyrosinemia • Storage Disorders – GSD, Wilson’s, Hemochromatosis

• Urea Cycle Defects

Etiology • Tumors • Hepatoblastoma, HCC, Sarcoma, Hemangioendothelioma

Etiology ◗

Diseases related to Hepatocytes • Miscellaneous • Cong. Fibrosis • Caroli • Cystic Fibrosis • HAL induced

Pediatric Liver Diseases Presenting Features ◗

Fulminant Liver Failure • • • •

Encephalopathy Jaundice Coagulopathy Multisystem Organ Failure

Pediatric Liver Diseases Presenting Features

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Chronic Liver Disease • • • • • • • •

Growth Failure Portal Hypertension--Bleeding Coagulopathy Jaundice Ascites Encephalopathy Protein Calorie Malnutrition Vitamin/ Mineral Deficiencies

Pediatric Liver Disease Diagnosis Clinical Features ◗ Serum Chemistry ◗ Imaging ◗

• US Scan • MRI

Isotope Scanning ◗ Liver Biopsy ◗

Pediatric Liver Disease Management ◗

Fulminant Liver Failure • • • • •

Supportive Prevention of Infection Specific Therapy Liver Transplantation Long term sequela

Pediatric Liver Disease Management ◗

Chronic Liver Failure • Supportive care/ Symptomatic • Surgical treatment for Biliary atresia • Supplemental therapy with vitamins • Palliation of Portal HTN with shunts • Liver Transplantation

Pediatric Liver Disease Management ◗

Metabolic Liver Diseases Replacement of deficient end product/ substrate • primary bile acid, cornstarch

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Enzyme inhibition and induction • Tyrosinemia-NTBC • Phenobarbitone

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Removal of Toxic Products • Iron chelation, Copper chelation, Benzoate and phenylacetate in Urea Cycle defects

Pediatric Liver Disease Management Metabolic Liver Diseases ◗ Dietary Restriction of substrate • Galactose and Fructose

Gene Therapy ◗ Organ Transplantation ◗

Pediatric Liver Disease Liver Transplantation Indications ◗ Contraindications ◗ Cadaveric ◗

• Whole • Split

Living related or unrelated ◗ Hepatocyte transplantation ◗

Liver Transplantation ◗

Pretransplant evaluation • Candidate • Donor • Multidisciplinary approach: Physicians, Coordinator, Social Worker, Pharmacist, Dietician

LRLTX Work-up ◗

Phase I: Recipient • • • • •

.Standard Transplant Evaluation Protocol .Hepatology Evaluation H&P .Identification of potential donors .UNOS PELD status .Absence of significant contraindication or medical problem • .Psychosocially stable

LRLTX Work-up The Concept of PELD ◗

PELD Score = 0.436(Age(<1yr))-0.687 x Loge (albumin g/dL) + 0.480 x Loge (total bilirubin mg/dL) + 1.857 x Loge (INR) +0.667 (Growth failure (<-2Std. Deviations present))

LRLTX Work-up The Concept of PELD UNetSM Listing Category 1. Status 1 2. PELD/MELD Score 3. Inactive

PELD Re-certification Score Recertification Lab Values > 25

Q 7 days

< 48 hrs old

24-19 Q 30 days

< 7days old

18-11 Q 90 days

< 14 days old

10-0

< 30 days old

Q year

LRLTX Work-up • Donor • • • • • • • • •

.Age >18 or <60yrs .Register patient .Financial clearance .Compatible ABO .Serologies, HIV .MSW Eval .Psych Eval .Pt. Advocate .LFT’s

LRLTX Work-up Donor Phase 1 • • • •

Laboratory tests .CXR .EKG .Hepatology Evaluation H&P

LRLTX Work-up Recipient • Absence of previous significant abdominal surgery • .Absence of major medical problems (ie.severe or uncontrolled, hypertension, hepatic cardiac renal or pulmonary disease, or active infection. • .Demonstrable significant long term relationship with recipient • .Absence of alcohol or illicit substance abuse

LRLTX Work-up Phase II ◗ Donor ◗

• • • • • •

Surgical H&P Triphasic CT MRI angiogram MRI cholangiogram MRI venogram Anesthesia preop eval

LRLTX Work-up Phase III ◗ ◗ ◗

Liver Biopsy Stress Echo Other tests or consults to clarify potential problems uncovered during evaluation

LRLTX: Physiological Considerations ◗

Graft to Recipient Body Weight GRBW +

Graft Outflow Capacity

Portal Hypertension

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Liver Transplantation ◗

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Donor Operation

Recipient Operation

Segmental Anatomy of the Liver

Preoperative Evaluation ◗

Donor • Vascular Anatomy • HA, PV, HV • Size of lateral segment-3D US • Parenchymal abnormalities • Fatty change, cirrhosis, tumors, gallstones

Role of Ultrasound in OLTX Preoperative evaluation ◗ Intraoperative evaluation ◗ Post-operative evaluation • Donor • Recipient ◗

Intraoperative Evaluation ◗

Donor • Location of LHV/MHV • HA • Benign tumors

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Recipient • Vascular Flows

Liver Transplantation ◗

Postoperative management • ICU • Floor • Immunosuppressants • Prograf • Cellcept • Steroids

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Discharge • Home Care

Post-operative Evaluation ◗ ◗ ◗ ◗ ◗ ◗

Routine Imaging for 3-5 days Hepatic Artery Portal Vein Hepatic vein Bile duct Hematomas/Bilomas

CHHC-UCSD Pediatric Liver Transplant Program ◗

First Pediatric Liver transplant in San Diego April 1999

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CHHC San Diego is one of the best Children’s Hospital in the country. It is a tertiary care 300 bedded hospital with maximum number of critical care beds.

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CHHC is committed to the development of Pediatric Abdominal Transplant Services

CHHC-UCSD Pediatric Liver Transplant Program CHHC’s Abdominal Transplant Team Surgeons, pediatric hepatologists, anesthesiologists critical care team, trained nurses, pharmacists, dietician, social worker, childlife specialist, translators, home care services and a fully equipped chemistry laboratory and 24 hour radiology services.

CHHC-UCSD Pediatric Liver Transplant Program Liver Transplant Process ◗ Donor and recipient work-up all in one facility ◗ ICU stay ◗ Postoperative follow-up and daily reports by Children’s Home care services upon discharge

CHHC-UCSD Pediatric Liver Transplant Program Liver Transplant Process ◗

Weekly outpatient clinics with pediatric gastroenterologists and hepatologists

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Team of physicians, transplant coordinators, translators, social workers, dieticians available in the clinic

CHHC-UCSD Pediatric Liver Transplant Program Academic activities ◗

Monthly candidate presentations multidisciplinary, M& M, research issues

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Quarterly Abdominal Transplant Steering committee meetings

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Abstract and paper presentations at National and International conferences

CHHC-UCSD Pediatric Liver Transplant Program ◗ ◗ ◗ ◗ ◗ ◗ ◗ ◗

Shorter waiting time for cadaveric patients Team experienced in Living related and split liver transplantation Well organized team Donor and recipient operation in the same hospital 100% success with Living related liver transplantation Cost-effective Minimal post-operative complication rate Metabolic service referral center

INNOVATIONS AND THE FUTURE

Innovations Hepatocyte Transplantation ◗ Artificial liver ◗ Stem cell therapy ◗ Drugs ◗

Liver transplant recipient Demi-Lee Brennan (c) with (l-r) Dr Stephen Alexander and Dr Stuart Dorney at Westmead Hospital in Sydney. (AAP: Paul Miller)

Questions