Management of liver failure
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Management of liver failure
Prof. Anupam SibalGroup Medical Director, Apollo Hospitals Group
Adjunct Professor of PaediatricsSchool of Medicine
University of Queensland, Brisbane, AustraliaSenior Consultant
Pediatric Gastroenterologist and HepatologistApollo Centre for Advanced Pediatrics
Indraprastha Apollo Hospital
Dr. Akshay KapoorPediatric Gastroenterologist and Hepatologist
Apollo Centre for Advanced PediatricsIndraprastha Apollo Hospital
April 2012
Fulminant hepatic failure
Onset of altered mental status within 8 weeks of initial symptoms in an otherwise healthy individual with no previous history of liver disease
Trey and Davidson, N Engl J Med 1968
April 2012
Classification
Hyper acute: within 1 week of onset of symptoms
Acute: between 8 days - 28 days
Sub acute: between 29 days to 12 weeks
O’grady et al, Lancet 1993
April 2012
Definition of ALF
“evidence of coagulation abnormality, usually an INR >1.5, and any degree of mental alteration (encephalopathy) in a patient without pre-existing cirrhosis and with an illness of < 26 weeks duration”
AASLD position paper on ALF, 2005
April 2012
ALF definition in children
Biochemical evidence of acute liver injury
Hepatic-based coagulopathy defined as PT ≥ 15 seconds or INR ≥ 1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy (HE) or PT ≥20 seconds or INR ≥ 2.0 regardless of the presence or absence of clinical HE
No known evidence of chronic liver disease
PALF study group J pediatric 2006
April 2012
Prevention of complications
Management of complications
Liver transplantation
April 2012
Medication
PPI, H2 blockers
Antibiotics
Mannitol
Lactulose
N-acetylcysteine
AASLD position paper on ALF, 2005
April 2012
diaFLUX dialyzer
April 2012
LT - key questions
Is there a chance of spontaneous recovery?
Is a transplant feasible?
Have irreversible complications occurred?
April 2012
King’s criteria for LT non-paracetamol causes
PT > 100 sec
Or 3 of the following :
Bilirubin >17.5 mg%
Age < 10 or > 40
PT > 50 sec
Symptoms to encephalopathy > 7 days
NANB or drug induced
O'Grady et al 1989
April 2012
FHF – King’s criteria for LT paracetamol overdose
pH < 7.3
or the following three factors :
PT > 100 secs
Creatinine > 3.5 mg/dl
Grade III or IV encephalopathy
O'Grady et al 1989
April 2012
INR ≥ 4
Bilirubin ≥ 13.8 mg/dl
Age < 2 yr
WBC > 9 X 109 / l
INR > 4
90 % correctly classified
Dhawan et al Pediatr transplant, 2011
April 2012
Apollo experience
INR > 4
April 2012
Chronic liver failure
No accepted definition
Associated with development of cirrhosis and its complications – malnutrition, PHT, bleeding esophageal varices, ascites, encephalopathy, HRS
Loss of synthetic properties of liver
April 2012
Hepatobiliary referrals 1.10.97 – 30.06.2011
624
1686
446
129
489
Neonatal Cholestasis
Acute Liver Disease
Chronic Liver Disease
Fulminant HepaticFailure
Miscellaneous
n = 3374
April 2012
Chronic liver diseasen = 446
Hepatitis B 189
Unknown 97
Hepatitis C 68
Wilson’s 31
Choledocal cyst 26
AIH 18
Others 17
April 2012
Therapy for hepatitis B
Interferon
Lamivudine
Adefovir
Telbivudine
Entecavir
Tenofovir
April 2012
Therapy for hepatitis C
Interferon
Pegylated IFN
Ribavarin
April 2012
Wilson disease
D-penicillamine
Zinc
Trientine
April 2012
Normal canaliculi PFIC
April 2012
April 2012
Nutritional support
Increase calorie intake 130 – 150 %
Protein intake 3 – 4 gm / kg
BCAA enriched
albumin infusions
Fat intake MCT / LCT ratio 50:50
essential fatty acids
Vitamins intake Fat soluble and water soluble
April 2012
Endoscopic variceal ligation
April 2012
April 2012
Indications for LT - clinical parameters
Recurrent variceal bleeding
Refractory ascites
Intractable pruritis
Growth retardation
Unacceptable quality of life
April 2012
Indications for LT - laboratory parameters
Prothrombin ratio (INR) > 1. 4
Indirect bilirubin > 6 mg/ dl
Albumin < 3.5 mg/ dl
Cholesterol < 100 mg/ d
April 2012
Actuarial survival post liver transplantation Birmingham pediatric liver transplant programme 1983 - 2005
0.00 5.00 10.00 15.00 20.00
Survival post transplant (years)
0.0
0.2
0.4
0.6
0.8
1.0
Cu
mu
lati
ve s
urv
ival
Fulminant (57)
Metabolic (25)
EHBA (187)
Kaplan Meier Curve
April 2012
LT in infants < 6 months
43 patients
Median weight 5.8 kg
Patient Survival (%)
1 year 90.7
2 year 87.2
Grabhorn E et al, Transplantation.2004;78(2):235-41
April 2012
Neonatal LT
Median age at transplant 15 days
Median weight 3.25 kg
11 transplants in 10 patients
5 years patient survival 80%
Grabhorn E et al. Transplantation.2008 15;86(7):932-936
April 2012
Is there a need ?
Why in India ?
Is it possible ?
April 2012
Need
Need for LT in 30% of children with liver diseases
Cirrhosis (45%)
Biliary atresia (38%)
FHF (11%)
Mehrotra et al Indian Pediatr 1999
April 2012
Need for liver transplantation
Satisfying criteria 358
NC 214
FHF 56
Unknown 39
Wilson’s 13
PFIC 13
Hepatoblastoma 6
Tyrosinemia 5
Crigler Najjar 5
HCC 3
BCS 3
Congenital hepatic fibrosis 1
April 2012
Need
2 per million
2500 children
April 2012
Why in India ?
Abroad
60 lakhs – 1.5 crores
additional cost
long waiting period
last priority
April 2012
Liver transplantation in India historical landmarks
11th Jan. 1998 1st pediatric attempt (cadaver)
15th Nov. 1998 1st successful pediatric liver transplant
17th Nov. 1999 1st successful left LRLT (pediatric) for FHF
17th July 2002 1st successful LR re transplant
16th Nov. 2007 1st pediatric cadaver transplant
12th Aug. 2008 Youngest liver transplant in India
April 2012
LT experiencen = 77
BA 30
Metabolic liver diseases 13
Cryptogenic 11
FHF 7
BCS 3
Congenital hepatic fibrosis 4
NNH 2
PVT 1*
Hep C 1
HCC 1
Poisoning 1
AIH 1
Hyper oxaluria 1
*One re transplant
April 2012
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95 100
40
74
16
61
0
50
100
150
200
250
300
350
400
450
500
1997-2006 2007 till date
Fit for LT Willing for LT Underwent LT Adult LT
The watershed
88
695
April 2012
What has contributed to success?
Better surgical expertise
Standardized post transplant care
Fewer complications
Better immunosuppresion
April 2012
What has changed in India?
Greater awareness
public
medical community
Improving outcomes
expanding indications
smaller babies
Greater acceptance
Cost has come down to 12 lakhs – 15 lakhs
April 2012
Building the bridge
April 2012
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Liver transplantation is possible
Indian skills
Indian minds
Indian infrastructure
April 2012
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