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
◗ 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
◗ 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
◗ Enzyme inhibition and induction
• Tyrosinemia-NTBC
• Phenobarbitone
◗ 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 Q year < 30 days old
 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 Portal _
Capacity Hypertension
Liver Transplantation

◗ 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

◗ Recipient
• Vascular Flows
 Liver Transplantation
◗ Postoperative management
• ICU
• Floor
• Immunosuppressants
• Prograf
• Cellcept
• Steroids
◗ 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

◗ 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.

◗ 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

◗ 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
◗ Quarterly Abdominal Transplant Steering
committee meetings
◗ 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