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Year : 2011  |  Volume : 16  |  Issue : 1  |  Page : 2-7

Pediatric liver transplantation: A report from a pediatric surgical unit

1 Department of Pediatric Surgery, Narayana Hrudayalaya Hospitals, Bangalore, India
2 Department of Pediatrics and Intensive Care, Narayana Hrudayalaya Hospitals, Bangalore, India
3 Department of Gastroenterology, Narayana Hrudayalaya Hospitals, Bangalore, India
4 Pediatric Solid Organ Transplantation, Alfred Dupont Children's Hospital, Delaware, USA

Date of Web Publication3-Jan-2011

Correspondence Address:
Sanjay Rao
Department of Pediatric Surgery, Narayana Hrudayalaya Hospitals, 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore - 560 099
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9261.74512

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Background: Liver transplantation is well established worldwide as an effective treatment for end-stage liver disease in children. Acceptance in India has been slow because of considerations of cost, infections, inability to support long-term care, and non-availability of expertise. Aim: This study was designed to report our experience with pediatric liver transplantation. Materials and Methods: Twenty-eight children underwent liver transplantation. Results: Biliary atresia was the commonest indication (n = 15) followed by metabolic liver disease. Twenty-six children had living donor transplants, mothers being the donors in a majority of these. Common surgical complications included bile leaks (n = 3) and vascular problems (n = 6). Common medical complications included infections, acute rejection, and renal failure. Overall, patient survival was 71%, while that for the last 14 cases was 92%. All survivors are doing well, have caught up with physical and developmental milestones and are engaged in age appropriate activities. Conclusions: The study demonstrates the feasibility of a successful pediatric liver transplant program in our country.

Keywords: Biliary atresia, chronic liver failure, living donor transplant, pediatric liver transplantation

How to cite this article:
Rao S, D'Cruz AL, Aggarwal R, Chandrashekar S, Chetan G, Gopalakrishnan G, Dunn S. Pediatric liver transplantation: A report from a pediatric surgical unit. J Indian Assoc Pediatr Surg 2011;16:2-7

How to cite this URL:
Rao S, D'Cruz AL, Aggarwal R, Chandrashekar S, Chetan G, Gopalakrishnan G, Dunn S. Pediatric liver transplantation: A report from a pediatric surgical unit. J Indian Assoc Pediatr Surg [serial online] 2011 [cited 2023 Mar 24];16:2-7. Available from: https://www.jiaps.com/text.asp?2011/16/1/2/74512

   Introduction Top

Pediatric liver transplantation is a well-established and effective option for treating children with end-stage liver disease. Unfortunately, due to various reasons, its acceptance has been slow in India. Although a handful of highly successful transplant programs exist in the country, they are primarily adult programs. As pediatric surgeons, we care for a large number of biliary atresia children who end up with end-stage liver disease and do not have the option of liver transplantation.

It was against this background that a dedicated pediatric liver transplant program was started at Narayana Hrudayalaya, Bangalore, under the leadership of the senior author (AJD). The program has now matured, and this article reports our experience in this very exciting and challenging area.

   Materials and Methods Top

Twenty-six children underwent a liver transplantation procedure at our center since 2005. Two other children were also transplanted by the same team earlier in another center. These 28 children formed the basis of this retrospective descriptive cohort study. The data were collected from patient records and dedicated databases maintained for this purpose.

   Results Top

Demographic data are summarized in [Table 1]. The indications for liver transplantation are listed in [Table 2].
Table 1: Demographic details of patients undergoing liver transplantation a

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Table 2: Indications for liver transplantation in the study cohort

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Graft profile

Only 2 of the 28 children received cadaveric grafts. One received size-matched whole organ, and the other received a reduced graft from an adult donor. In the remaining, the grafts were living donor grafts. The details are summarized in [Table 3].
Table 3: Type of liver graft used in study cohort

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Donor profile

Twenty-six children received grafts from living donors. The donors were mothers (19), fathers (4), second-degree relatives (2), and altruistic (1). All donors made rapid recovery after the donor procedure and have returned to their routine activities. There has been no long-term morbidity. Four donors had problems in the early postoperative period: (a) one donor required re-exploration after 12 h for a bleed in the drain; no active bleeder was found, (b) one had prolonged bile drainage that responded to pigtail drainage, (c) one had a transient ischemic attack that rapidly recovered and no etiology was found on extensive testing, and (d) one lady had a minor wound infection that responded to regular dressings.

Recipient procedure

The recipient operation is a formidable procedure, the details of which are beyond the scope of this article. Briefly, the steps include anesthetic preparation with special attention to vascular access, temperature regulation, and invasive monitoring. The abdomen is entered through an inverted 'T' incision in the upper abdomen. Previous Kasai operations, portal hypertension, ascites and serositis from bacterial peritonitis make this stage especially challenging. The liver is dissected free from its moorings and mobilized. The hepatic artery and portal veins are dissected well into the hilum and looped. The retrohepatic inferior vena cava is dissected from the liver and hepatic veins identified and dissected free. The bile duct or roux-loop is identified and dissected off the portal area and divided. The hepatic artery and portal vein are then clamped and divided close to the liver. The IVC is clamped above and below the liver and the diseased liver explanted. This anhepatic phase is a critical time during the procedure as all venous return from the lower body is cut-off. The engraftment starts with anastomosing the graft hepatic vein to the IVC-usually at the level of the native hepatic veins. The portal vein is then anastomosed and re-perfusion established. This period of re-perfusion is associated with serious hemodynamic instability due to the load of volume, acids and potassium that is swept into the system from the bowel, graft, and lower body. After a period of stabilization, the hepatic artery is anastomosed. Biliary reconstruction is then carried out, usually to the previously constructed roux-loop. The peritoneum is drained and child returned to the intensive care unit.

Immune suppression

Our immune suppression protocol is based on a combination of steroid and tacrolimus, a calcineurin inhibitor (CNI). The steroid is rapidly tapered and weaned off by 3 months. Tacrolimus is used for maintenance. Basilaximab induction and mycophenolate mofetil (MMF) are used in children who have or are at risk of renal impairment. MMF is also used as a second maintenance agent in addition to tacrolimus in children who have had a documented rejection episode.

Surgical complications in the postoperative period

The postoperative period is often stormy and difficult. The various surgical problems encountered during this period are detailed below.


A combination of portal hypertension, previous surgery, pre-existing coagulopathy and prolonged surgery results in a high risk of postoperative bleeding. Three children had bleeding from the drains significant enough to warrant re-exploration. In one child, a tributary in the retroperitoneum was identified and controlled, in the remainder, no obvious source could be identified. Children are anticoagulated with deltaparin if their INR gets to <2. They are also on aspirin once enteral feeds are commenced. A combination of clinical observation, coagulation studies, and thromboelastogram is used to keep the children in an optimal state of anticoagulation-that which prevents bleeding and also minimizes the risk of thrombosis-this is a fine balance indeed.

Vascular complications

(a) Hepatic artery thrombosis (HAT): Two children in our series developed HAT on the postoperative days 1 and 3. Both these children were re-explored urgently and arterial flow was reestablished. Both the children are doing well, and there have been no long-term effects on the grafts.

(b) Portal vein problems: These include:

(i) Early portal vein thrombosis. This has been identified in two children. In one child, the anastomosis was redone and widened with a vein patch. In the other, the vein could not be recanalyzed. In this child, the IVC was divided and distal IVC anastomosed to the portal vein inflow of the graft. However, the child succumbed.

(ii) Late portal vein narrowing was seen in one child. This boy developed progressive splenomegaly, and imaging revealed anastomotic stenosis in the portal vein. This responded to endovascular balloon dilatation.

(c) Hepatic outflow problems: One child developed a partial obstruction to the venous outflow resulting in graft congestion and swelling. The child settled down after a re-operation to reposition the liver and create a ventral hernia.

Intestinal obstruction and pathology

(a) Five children developed intestinal problems in the postoperative period. They developed intestinal obstruction that required surgical intervention. Of these, one child had to be re-explored on three occasions. All five of these children had had a Kasai operation earlier and the child requiring multiple re-explorations had had an additional laparotomy in the neonatal period for a jejunal atresia. This child and another had prolonged intestinal dysfunction and required prolonged total parentral nutrition (TPN). Intestinal obstruction in the early post-transplant phase results in a disruption of the biliary anastomosis as was noted in two of these four cases. An antecolic roux loop was used in two patients in this group.

(b) One child developed invasive cytomegalovirus (CMV) induced jejunal perforation. A laparotomy was performed and perforation closed.

Biliary problems

A duct-to-duct reconstruction was performed in two children. All the rest had a roux loop reconstruction. One child had four ducts, 6 had two ducts and the remainder had a single duct to roux loop drainage. Three children had biliary leaks. Two required surgical repair and one responded to pigtail drainage.

Medical issues in the post-transplantation period

  1. Acute rejection: Four children developed acute rejection in the early postoperative period. All were commenced on a pulse steroid regimen after biopsy confirmation of the rejection. In two of these children, MMF was added as a CNI sparing agent in lieu of renal dysfunction.
  2. Pulmonary pathology: Three children required prolonged ventilation for pulmonary hypertension secondary to hepatopulmonary syndrome. Two underwent tracheostomy to facilitate care and weaning.
  3. Renal pathology: Renal dysfunction was seen in three children. One child required renal replacement therapy with CRRT. Another boy developed falling GFR 1 year post-transplantation-this was thought to be related to tacrolimus toxicity and immunosuppression was modified.
  4. Sepsis: It was seen in 70% and fungal sepsis was noted in three children.
  5. Other infections: Other infections noted include one each of tuberculosis, dengue fever, malaria, and measles.


The overall survival after liver transplantation in our group is 71%. Twenty of the 28 patients are alive and well after their transplantation. There have been eight deaths. Five deaths were within 28 days of surgery (periop)-causes included primary non-function, abdominal compartment syndrome, portal vein thrombosis, sepsis, and resistant pulmonary hypertension. Three children succumbed to various illnesses later on. One had a Burkitt's lymphoma, one had cyclosporine-induced convulsion, and the third developed sudden cardiac arrest after a recent upper respiratory infection.

However, if the cases are grouped into two groups, as listed in [Table 4], the survival improved from 50% in the first half to 92% in the second half. The one death in the second group was an unexplained cardiac arrest in a child who had undergone a LDLT from his mother 3 months previously. He developed an upper respiratory infection and succumbed while on his way to the hospital.
Table 4: Outcomes of patients undergoing liver transplant in this study

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All the survivors are in good health. They have caught up with physical and developmental milestones and activities.

   Discussion Top

The program demonstrates liver transplant as a feasible option for children with liver disease in our country. Increasing experience has demonstrated improving survivals.

Biliary atresia causing chronic liver disease was the commonest indication for transplantation in half of the children, followed in frequency by metabolic liver disease. This is similar to experience of other larger programs. [1],[2] Patients were often small-the median weight being 8.5 kg and a median age of about 2 years. This is a reflection of the poor health of these children. Children with chronic and end-stage liver disease are invariably malnourished and in very poor health. This makes them very high risk for the transplantation. Optimization of nutritional deficiencies should form a part of the ongoing care of these children, irrespective of whether they come to transplant or not. Children weighing less than 10 kg are a high-risk group to transplant. Fifteen of the 28 children in our series weighed less than 10 kg and outcomes in this group were at par with the rest.

Living donor grafts account for over 90% of transplants. This is in keeping with experience in most Asian countries. [3] As most children require only a left lateral segment graft, the morbidity and risks to the donor are much less than those donating their right lobes. Living donor transplants are ideally suited to children as it allows for a planned procedure, allows for a near optimal size graft for the child, reduces the risk for the donor, and the incidence of rejection is reduced.

Mothers form the predominant donors in our group. However, our recent experience has shown that more fathers are willing to be donors. Our preferred policy is to use group-specific donors and availability of such is often a limiting factor. This trend increases the donor pool and gives us more options to choose either parent or the possibility of re-transplantation. Altruistic and unrelated donation in the case of liver transplantation is an ethically difficult problem to consider as the associated risks with the donor procedure remain significant. Ideally, we should strive to develop the deceased donor program with the expertise to use split-liver grafts and reduced grafts. We have had only one instance where a liver from a 47-year-old deceased donor was reduced for a child weighing 12 kg. Most patients with chronic liver disease, especially after biliary atresia, are in very poor general health. They have already had surgery before and have since developed portal hypertension, ascites, bacterial peritonitis, and complications from chronic malnutrition. They have marginal renal and pulmonary functions. They have often been hospitalized and are colonized with hospital pathogens. Performing a liver transplant naturally puts them at risk of a variety of complications. [3]

Bleeding is common. They are coagulopathic to start with and continue to remain so until the liver begins synthetic functions and sepsis is controlled. However, a majority can be managed conservatively and re-explorations for bleeding are rare. Careful management of their coagulation status is vital, and the thormboelastogram provides a functional indicator of the coagulation status in these children.

The incidence of HAT in our series was 7% (n = 2). There is a high risk of HAT in the postoperative period due to the following reasons: (a) small caliber vessels and (b) low flow states due to splanchnic vasoconstriction secondary to low fluid status, diuretic use, hemodynamic instability, imbalanced coagulation, and disseminated intravascular coagulation (DIC). HAT in the early postoperative period can potentially impact graft and patient survival. The two children who were recanalyzed after HAT have been on the follow-up for over 2 years and are well. Delayed effects of arterial insufficiency such as biliary strictures have not been detected. Wamaar et al. reported a HAT incidence of 13.7%, about a third of who were recanalyzed successfully. [4]

Incidence of portal vein thrombosis is reported as 4%. [1] The portal vein in children, especially after a Kasai procedure is often narrow, fibrotic and often encased in inflammatory lymph nodes. A high risk of portal vein thrombosis exists in these children. Acute portal vein thrombosis in the early postoperative period can be devastating as is demonstrated in the one child who developed it in this series. Late portal vein stenosis is usually anastomotic and children present with features of portal hypertension. Transhepatic, endovascular balloon dilatation is the procedure of choice. [5] Other procedures such as operative repair, portocaval shunts have an unacceptably high morbidity and graft loss rate.

Biliary problems are the commonest surgical problems in the postoperative period with a reported incidence of 20%. [3] The bile ducts on the graft are often very small and multiple. A Roux-en-Y drainage of all these ducts is the procedure of choice. Occasionally, a duct-to-duct anastomosis is possible, but care need to be taken to preserve vascularity of the recipient duct during the explantation procedure. Children with arterial problems often manifest with bile leaks as the biliary blood supply is almost entirely from the hepatic artery. Intestinal obstruction in the early postoperative period can result in dilatation of the roux loop and disruption of the new biliary enteric anastomosis as was noted in two children in the series. The majority of the bile leaks respond to drainage and time.

Intestinal problems in the postoperative period are common. A combination of previous exploration for the Kasai procedure and serositis increases the risk of adhesive obstruction in these children. Two children with antecolic roux loops were particularly difficult to manage. When the roux loop is freshened and reused to drain the graft biliary tree, the pull on the mesentery of this loop compresses the transverse colon resulting in obstruction. We now follow a policy of converting an antecolic loop to a retrocolic one prior to the biliary enteric anastomosis. This intestinal failure needs time to recover and often TPN, along with all its problems, becomes unavoidable. Intestinal perforation is also reported. [3] One child developed small bowel perforation due to invasive CMV infection.

Acute rejection was seen in 14% (n = 4). All responded to pulse steroid and intensification of immune suppression. There has been no long-term adverse effects in these patients and their course has been similar to those who did not have acute rejection. In the LDLT scenario, acute rejection is less common and usually completely reverses with adequate therapy. Incidence of acute rejection has been reported to be between 40% and 70%. [1],[3]

Other medical problems such as pulmonary failure, renal dysfunction, and coagulopathy are common in the immediate postoperative period. A detailed review is beyond the scope of this article. Suffice to say that a majority of these problems are controlled and reversed once the graft liver begins to function normally. Extreme caution is necessary when administering any medications as these could interact with immune suppression and raise or lower serum levels and could cause additive renal damage. Being a tropical environment, children are exposed to the usual tropical infections-malaria, measles, dengue fever, and tuberculosis have all shown up. Once again, treatment needs to be tailored to reduce exposure to drugs that interact with immune suppression and also lay undue stress on the new liver and kidneys.

Overall survivals have been 70%. Early in the program, there were five deaths in the postoperative period (defined as up to 28 days post-op). Sepsis, primary nonfunction, and vascular problems are the usual causes of death in the early post-transplant period. Late complications include chronic rejection, [6] renal damage in up to 20%, [7] drug toxicity, sepsis, and post-transplant lympho-proliferative disease. [8]

Over the last 14 cases, there has been no postoperative mortality. All children have been successfully managed and discharged. This is a reflection of maturing of the program and completion of the steep learning curve at all stages of management. Refining of protocols has made long-term care more thorough and cost efficient. All surviving children are doing well-they have caught up with growth and development and are pursuing age appropriate activities. It is often the sickest children who make the most dramatic recoveries. Survival after liver transplantation has been reported as 91%, 87%, and 81% at 1, 5, and 10 years, respectively. [9] If the child makes it past the first year after transplant, it is very likely that he will survive to 10 years.

   Conclusions Top

Our experience demonstrates the feasibility of liver transplantation in children with end-stage liver disease in India. The early survival and complication rates are at par with other established programs, even in those weighing less than 10 kg. Complications are frequent in the early postoperative period; however, most are treatable. A majority of children after a liver transplant can expect an excellent quality of life and longevity. There are several special issues that the program has had to address. These include limited financial resources, skepticism from the medical and lay community, problems specific to our country such as tuberculosis and dengue. However, all these issues have been addressed systematically and this is reflected in the improving outcomes and more physicians and parents opting for this treatment.

   References Top

1.Vila-Melendez H, Heaton ND. Liver transplantation: the surgical view. Postgrad Med J 2004;80:571-6.  Back to cited text no. 1
2.Muiesan P, Vergani D, Mieli-Vrgani G. Liver transplantation in children. J Hepatol 2007;46:340-8.  Back to cited text no. 2
3.Takahashi Y, Nishimoto Y, Matsuura T , Hayashida M, Tajiri T, Soejima Y, et al. Surgical complications after living donor liver transplantation in patients with biliary atresia: a relatively high incidence of portal vein complication. Pediatr Surg Int 2009;25:745-51.  Back to cited text no. 3
4.Warnaar N, Polak WG, de Jong KP, de Boer MT, Verkade HJ, Sieders E, et al. Long -term results of urgent revascularization for hepatic artery thrombosis after pediatric liver transplantation. Liver Transpl 2010;16:812-4.  Back to cited text no. 4
5.Funaki B, Rosenblum JD, Leef JA, Hackworth CA, Szymski GX, Alonso EM, et al. Portal Vein Stenosis in children with segmental liver transplants. Am J Radiol 1995;165:161-5.  Back to cited text no. 5
6.Bucuvalas J. Long term outcomes in pediatric liver transplantation. Liver Transpl 2009;15:S6-S11.  Back to cited text no. 6
7.Avitzur Y, De Luca E, Cantos M, Jimenez-Rivera C, Jones N, Fecteau A, et al. Health status ten years after pediatric liver transplant-looking beyond the graft. Transplantation 2004;78:566-73.  Back to cited text no. 7
8.Ganschow R, Schulz T, Meyer T, Broering DC, Burdelski M. Low dose immunosuppression reduces the incidence of posttransplant lymphoproliferative disease in pediatric liver graft recipients. J Pediatr Gastroenterol Nutr 2004;38:198-203.  Back to cited text no. 8
9.Mention K, Lahoche-Manucci A, Bonnevalle M, Pruvot FR, Declerck N, Foulard M, et al. Renal function outcome in pediatric liver transplant patients. Pediatr Transpl 2005;9:201-7.  Back to cited text no. 9


  [Table 1], [Table 2], [Table 3], [Table 4]

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