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Indian Pediatr 2011;48: 51-54 |
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Outcome of Live Donor Liver Transplantation in
Indian Children with Bodyweight <7.5 kg |
Satvinder Kaur, Nishant Wadhwa, Anupam Sibal, Nameet Jerath and Shridhar
Sasturkar*
From the Apollo Centre of Advanced Pediatrics
and *Department of Transplant Surgery, Indraprastha Apollo Hospital, New
Delhi, India.
Correspondence to: Prof Anupam Sibal, Senior Consultant,
Paediatric Gastroenterologist and Hepatologist, Indraprastha Apollo
Hospitals, N. Delhi 110 076, India.
Email:
[email protected]
Received: September 4, 2009;
Initial review: November 13, 2009;
Accepted: March 10, 2010.
PII: S097475590900611-2
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Abstract
This case-series analyzed the outcome of live donor
liver transplantation (LT) performed in children <7.5kg from January
2008 to June 2009 at our center. Five patients (3 males, 2 females, mean
age, 8.2 ± .4 months; mean weight 6.8 ± 0.4 kg) underwent LT. The
indications of LT included biliary atresia (3) and idiopathic neonatal
hepatitis (2). Postoperative complications included acute rejection (1),
portal venous thrombosis (1), bile leak (1), severe hypertension (1) and
bacterial sepsis (4). There were no donor related complications. The
median follow-up duration is 11 months with patient and graft survival
rates of 100% each, respectively.
Key words: Child, India, Live-related liver transplantation,
Outcome.
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I n the current era, 10-year patient
and graft survival rates of pediatric liver transplantation (LT) are 88
and 81%, respectively [1]. LT in small children still poses a surgical and
medical challenge. Greater than 80% survival in young recipients has also
been reported recently [2,3]. In this series, we describe our experience
of live donor LT performed in children weighting less than 7.5 kg.
Methods
A retrospective analysis of case-records of children
<7.5kg with indications for LT enrolled sequentially from January 2008 to
June 2009 was undertaken. Pre transplant assessment included blood
cultures, viral serologies (HIV, HBV, HCV, HAV, CMV, HSV, VZV), ultrasound
doppler, CT angiography of abdomen, dental and cardiac evaluation in
addition to liver function tests, hemogram and serum biochemistry.
Parents/blood relatives were evaluated after informed
consent. A psychiatric assessment was performed in every donor. A CT
angiography of liver for volumetry was obtained to assess available graft
size. All grafts were obtained from left lateral segments (II,III) of
living related donors. All transplants at our hospital are approved by an
authorization committee.
Postoperative immunosuppression was instituted with
triple-drug therapy regime, which consisted of steroids, cyclosporin and
mycophenolate. Steriods were given as an intraoperative bolus of
methylprednisolone (30 mg/kg) tapered over 5 days. Thereafter,
prednisolone was started at a dose of 8 mg/kg tapered to 2 mg/kg over a
period of five days. It was slowly tapered over next three months. Pulse
methylprednisolone therapy was given at a dose of 30 mg/kg for three days
in patients with suspicion/evidence of acute rejection. Cyclosporin was
used in an oral dose of 2 mg/kg/dose every 12 hourly. The target trough
level was 150-250 ng/mL. It was changed to tacrolimus in a patient in whom
rejection was confirmed with the target trough level of 5-10 ng/mL.
Mycophenolate was administered in a dose of 600mg/m 2
in two divided doses.
Results
Five children <7.5kg (3 males) underwent live-related
LT (Table I). According to the Indian Academy of Pediatrics
classification of malnutrition, two children each had grade II and I
malnutrition, respectively. Of three patients with biliary atresia, two
had prior portoenterostomy and one had cholecystojejunostomy done at
another centre. Living donors were the father in three cases and a
maternal uncle and an aunt in one case each. The mean age and weight of
donors were 31 ± 6.3 years (range 21-41) and 64.2 ± 9.1 kg (range 51-75),
respectively.
TABLE I
Clinical Profile of the Five Patients
Mean age (mo) |
8.2 ± 2.4 (6-12) |
Mean weight (kg) |
6.8 ± 0.4 (6.2-7.4) |
Diagnosis |
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Extrahepatic biliary atresia |
3 |
Idiopathic neonatal hepatitis |
2 |
Mean Total serum bilirubin (mg/dL) |
27.7 ± 14.0 (12-48.3) |
Mean International normalized ratio |
2.1 ± 1.2 (1.3-4.6) |
Mean graft to recipient weight ratio |
4.2 % (3.3-5) |
Mean duration of surgery (h) |
12 |
Mean Cold ischemic time (min) |
101 (40-160) |
Mean Warm ischemic time (min) |
34.2 (25-45) |
One patient had an inferior vena cava (IVC) stenosis
below the right hepatic vein (HV) insertion and required a venoplasty.
This patient had a large left hepatic artery (HA), atrophy of right lobe
along with hypertrophy of left lobe. All patients with prior biliary
surgery had dense adhesions at porta. Adhesionolysis required meticulous
dissection. Dissection was performed through the sub capsular plane of
liver to avoid injury to the bowel. Another difficulty during hepatectomy
was thin small hepatic veins draining directly into IVC. Portal venous
(PV) reconstruction in these patients is known to be technically
demanding. Two patients had a standard graft PV to the main PV anastomosis.
We mobilized main PV up to the confluence of superior mesenteric vein and
splenic vein and performed the anastomosis near the confluence. One
patient required a PV interposition graft obtained from the internal
jugular vein. One patient had a small main PV with a large coronary vein
draining near the confluence. The graft PV was implanted to the common
channel of main PV and coronary vein. Wedge shaped slit of lateral angles
of PV were useful in case of size mismatch. Arterial reconstruction was
performed between the graft artery and right HA. Biliary reconstruction
was performed by Roux-en-Y hepaticojejunostomy [4,5].
TABLE II
Postoperative Course and Early Complications
Complications |
Frequency |
Surgical |
bile leak |
1 |
acute rejection |
1 |
portal venous thrombosis |
1 |
Medical complications |
severe hypertension |
1 |
bacterial sepsis |
4 |
Mean post LT stay (d) |
21.6 + 4.5 |
Median follow up (mo) |
11 |
Survival |
100% |
Postoperative early complications: Post-operative
complications are listed in Table II. Acute rejection was
identified in one patient on postoperative day (POD) 7. The diagnosis was
confirmed with a liver biopsy. The patient required change of immuno-suppressive
therapy from CYC to TAC along with methylprednisolone bolus therapy.
PV thrombosis was identified in one child on second
POD. Immediate thrombectomy was performed but the patient had recurrent
thrombosis and the graft was salvaged by a retrohepatic cavoportal
anastomosis [6]. A non-anastomotic bile leak was observed in a solitary
patient on 20th POD. He responded successfully to a percutaneous drain
insertion.
Severe hypertension was observed in one child, which
responded to medical management. Infectious complications were observed in
4 (80%) patients. These included blood stream sepsis, pneumonia and
urinary tract infection. The organisms isolated included E.coli,
Acinetobacter, Pseudomonas and Klebsiella in one child each. No fungal or
viral infections were observed. No deaths were recorded.
The mean duration of post LT hospital stay was 21.6 ±
4.5 days (range 17-30) with intensive care stay of 3-5 days. There was no
donor related mortality or complications. All the donors were discharged
on 7-10 POD.
Late complications and outcome: Abscess formation
was seen at the site of BCG vaccination in a solitary patient 4 month
following transplant at 9 months of age, which resolved with oral
antibiotics. There were no other immunosuppression related complications.
No late vascular occlusions have been documented. All patients are well
with no evidence of chronic graft rejection or dysfunction and mean AST,
ALT and TSB levels are 30.0 ± 4.7U/L, 36.6 ± 5.1U/L, 0.32 ± 0.11mg/dL,
respectively. At a median follow-up of 11 months (range, 6.7-15), our
patient and graft survival rates are 100% each, respectively.
Discussion
LT still remains a significant challenge with
financial, follow up and survival implications especially, in small
children. Data from developing countries addressing these concerns is
scant. While it has been ten years since the first successful pediatric LT
was performed in India in our unit [7], the outcome of LT in small
children has not been reported from Indian subcontinent. In concordance
with what has been reported previously, extrahepatic biliary atresia with
failed Kasai procedure was the commonest indication [8,9].
In the absence of availability of cadaveric donors, living related liver
donation is the only realistic option in our country.
Literature suggests that infections are the principal
complications in pediatric LT candidates, occurring in 60-70% of cases
[10]. Significant bacterial infections that required therapy in the
perioperative period despite antibacterial prophylaxis were seen in 4
(80%) patients. The post-transplantation hospital stay was similar to
other pediatric reports, where the mean stay varied from 17-24 days [11].
With improvement in perioperative care, the length of post LT hospital
stay has been reduced over the last 10 years from a maximum of 68 days to
30 days. We report 100% survival in children <7.5 kg.
In our institute, the estimated cost of LT is
Rs.12-15 Lakhs (including medical and
surgical management of recipient and donor), which is significantly lower
than the average expenditure incurred in developed countries. Still poor
financial status, lack of awareness, delayed referral, a poorly developed
cadaveric program, and limited social-support groups are major hindrances,
which need to be overcome to promote LT in India [12].
Contributors: SK and SS collected, analyzed
the data and drafted the paper. NW and NJ helped in drafting the article
and revising it critically for important intellectual content. AS
conceived the study and revised the manuscript for important intellectual
content, and approved the final version. He will act as guarantor of the
study. The final manuscript was approved by all authors.
Funding: None.
Competing interests: None stated.
What This Study Adds?
• Outcome of small pediatric recipients (<7.5 kg)
undergoing living related liver transplant is excellent in the short
term.
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