Objectives: The ideal ratio between liver transplant graft mass and recipient body weight is unknown, but the graft probably must weigh 0.8% to 2.0% recipient weight. When this ratio > 4%, there may be problems due to large-for-size transplant, especially in recipients < 10 kg. This condition is caused by discrepancy between the small abdominal cavity and large graft and is characterized by decreased blood supply to the liver graft and graft dysfunction. We evaluated our experience with large-for-size grafts.

Materials and Methods: We retrospectively evaluated 377 orthotopic liver transplants that were performed from 2001-2014 in our center. We included 188 pediatric transplants in our study.

Results: There were 58 patients < 10 kg who had living-donor living transplant with graft-to-body-weight ratio > 4%. In 2 patients, the abdomen was closed with a Bogota bag. In 5 patients, reoperation was performed due to vascular problems and abdominal hypertension, and the abdomen was closed with a Bogota bag. All Bogota bags were closed in 2 weeks. After closing the fascia, 10 patients had vascular problems that were diagnosed in the operating room by Doppler ultrasonography, and only the skin was closed without fascia closure. No graft loss occurred due to large-for-size transplant. There were 8 patients who died early after transplant (sepsis, 6 patients; brain death, 2 patients). There was no major donor morbidity or donor mortality.

Conclusions: Large-for-size graft may cause abdominal compartment syndrome due to the small size of the recipient abdominal cavity, size discrepancies in vascular caliber, insufficient portal circulation, and disturbance of tissue oxygenation. Abdominal closure with a Bogota bag in these patients is safe and effective to avoid abdominal compartment syndrome. Early diagnosis by ultrasonography in the operating room after fascia closure and repeated ultrasonography at the clinic may help avoid graft loss.

Key words : End-stage liver disease, Infant, Pediatric, Treatment

Introduction

Liver transplant is the best treatment for end-stage liver disease in children. Advances in surgical techniques, intensive care, and immunosuppressive therapy allow this complex procedure to be performed in young and small infants. The ratio between the liver graft mass and recipient body weight (GBWR) is very important for living-donor liver transplant. The ideal GBWR is unknown, but it is believed that the graft must weigh 0.8% to 2.0% recipient body weight.¹ When this ratio > 4%, the graft is termed a large-for-size graft (LFSG), and problems caused by an LFSG are termed large-for-size syndrome (LFSS). This condition is observed especially in recipients weighing < 10 kg.² In this study, we evaluated our experience with LFSG.

Materials and Methods

We retrospectively evaluated 377 orthotopic liver transplants that were performed from 2001-2014 in our center. We included 188 pediatric liver transplants in our study. Data for recipients with body weight < 10 kg were reviewed retrospectively. Data included age, sex, etiology of liver disease, Child-Pugh score, pediatric end-stage liver disease (PELD) score, survival, and postoperative treatment of LFSS.

In all patients, intraoperative Doppler ultra­sonography was performed after closure of the abdomen, and Doppler ultrasonography was performed twice daily at the clinic during the first 7 days after surgery. After transplant, all patients were treated with the same immunosuppression protocol including tacrolimus, mycophenolate mofetil, and prednisolone. No protocol liver biopsy specimens were obtained, and biopsies were performed only for investigation of biochemical abnormalities such as elevated serum transaminase or bilirubin levels.

Results

There were 58 patients with body weight < 10 kg (mean weight, 7.8 ± 1.44 kg; range, 4-10 kg) and GBWR > 4%. All patients had living-donor living transplant. There were 35 male and 23 female patients. The most common indication for liver transplant was biliary atresia in 30 patients (51.7%). The other indications for liver transplant were progressive familial intrahepatic cholestasis type 2 (9 patients) and type 1 (2 patients), neonatal hepatitis (3 patients), Alagille syndrome (3 patients), Crigler-Najjar syndrome type 1 (4 patients), cryptogenic cirrhosis (1 patient), hepatoblastoma (2 patients), hepatic metastasis of cystic neuroblastoma (1 patient), cytomegalovirus hepatitis (1 patient), fulminant hepatitis A (1 patient), and tyrosinemia type 1 (1 patient). The mean Child-Pugh score was 8.9 ± 1.76 and PELD score was 24.1 ± 9.2.

The LFSS occurred in 18 patients. After closing the fascia in 10 patients, we diagnosed vascular problems (kinking) in the operating room by Doppler ultrasonography, and only the skin was closed without fascia closure. After the skin was closed, Doppler ultrasonography was repeated and the patients were taken to the intensive care unit. There were 5 patients who were reoperated for hernia at 1 year after transplant. The families of other 5 patients did not want a hernia operation. In 2 patients, the abdomen was closed with a Bogota bag at the first operation. There were 5 patients who were reoperated due to vascular problems and abdominal hypertension, and the abdomen in these patients was closed with a Bogota bag. All abdomens were closed in 2 weeks. In 1 patient, we reduced the graft volume using a stapler after the vascular anastomosis was completed.

No vascular thrombosis or graft loss occurred due to LFSS. Early after surgery, only 1 patient had a major abdominal infection and died from sepsis. Graft survival was 95% at 5 years and 89% at 10 years. There was no major donor morbidity or donor mortality.

Discussion

In LDLT or split liver transplant, GBWR < 0.8% is associated with a higher incidence of postoperative liver dysfunction.^3-5 In pediatric liver transplant, the use of an LFSG (GBWR > 4%) may cause graft damage such as vascular complications and necrosis due to an insufficient blood supply to the graft.^6,7

The main problem with an LFSG may include the risk of abdominal compartment syndrome due to the small size of the recipient abdominal cavity, size discrepancies in vascular caliber, insufficient portal circulation, and disturbance of tissue oxygenation.⁸

Some liver transplant centers reduce the graft into a monosegmental or hyperreduced graft. The graft reduction can be performed in situ, during the donor operation, or as a back table procedure with use of segment II or III as a graft.^9-13 In our series, we performed reduction after the vascular anastomosis was finished in 1 patient who weighed only 5 kg. An advantage of this technique is that when the liver is placed in the abdominal cavity, reduction is not performed when it is not required. Another advantage is that bleeding areas can be seen after the anastomosis is completed and easily controlled. In addition, this avoids a prolonged donor operation time that may occur when graft volume reduction is performed during the donor operation.

Reduction of the graft has several disadvantages for both donor, in case of in situ reduction, and recipient. In situ reduction in the donor requires a longer operating time and has an increased risk of biliary leakage and bleeding. For the infant recipient, there are increased risks of biliary leakage from the parenchymal surface, impaired venous drainage, and longer cold ischemia time with graft reduction outside the body.¹³ To avoid this complication risk, we chose the Bogota bag technique or skin closure without fascia closure in our patients. The major complication of the skin closure technique was the development of hernia, which required a second operation but did not affect graft survival. In our series, we repaired the hernias at 1 year after liver transplant. We did not use synthetic grafts, and all hernias were repaired with anatomic herniorrhaphy techniques.

Some studies have reported severe vascular problems, early graft loss, and graft necrosis because of direct pressure on the liver parenchyma using large grafts.^14,15 In our study, we did not have any graft loss, graft necrosis, or vascular thrombosis due to LFSS. However, vascular kinking was observed in 15 patients, and this was treated with Bogota bag technique or skin closure without fascia closure.

In conclusion, skin closure alone or abdominal closure with a Bogota bag in these patients is safe and effective to avoid abdominal compartment syndrome. Early diagnosis by intraoperative ultra­sonography after fascia closure and repeated postoperative ultrasonography in the clinic may help avoid graft loss.

References:

1. Leal AJ, Tannuri AC, Belon AR, et al. A simplified experimental model of large-for-size liver transplantation in pigs. Clinics (Sao Paulo). 2013;68(8):1152-1156.
2. Shehata MR, Yagi S, Okamura Y, et al. Pediatric liver transplantation using reduced and hyper-reduced left lateral segment grafts: a 10-year single-center experience. Am J Transplant. 2012;12(12):3406-3413.
3. Hill MJ, Hughes M, Jie T, et al. Graft weight/recipient weight ratio: how well does it predict outcome after partial liver transplants? Liver Transpl. 2009;15(9):1056-1062.
4. Glanemann M, Eipel C, Nussler AK, Vollmar B, Neuhaus P. Hyperperfusion syndrome in small-for-size livers. Eur Surg Res. 2005;37(6):335-341.
5. Yan L, Wang W, Chen Z, et al. Small-for-size syndrome secondary to outflow block of the segments V and VIII anastomoses - successful treatment with trans-splenic artery embolization: a case report. Transplant Proc. 2007;39(5):1699-1703.
6. Shirouzu Y, Kasahara M, Morioka D, et al. Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: the Kyoto experience. Liver Transpl. 2006;12(8):1224-1232.
7. Sieders E, Peeters PM, TenVergert EM, et al. Early vascular complications after pediatric liver transplantation. Liver Transpl. 2000;6(3):326-332.
8. Kasahara M, Kaihara S, Oike F, et al. Living-donor liver trans­plantation with monosegments. Transplantation. 2003;76(4): 694-696.
9. Srinivasan P, Vilca-Melendez H, Muiesan P, Prachalias A, Heaton ND, Rela M. Liver transplantation with monosegments. Surgery. 1999;126(1):10-12.
10. Kasahara M, Uryuhara K, Kaihara S, et al. Monosegmental living donor liver transplantation. Transplant Proc. 2003;35(4):1425-1426.
11. Strong R, Lynch S, Yamanaka J, Kawamoto S, Pillay P, Ong TH. Monosegmental liver transplantation. Surgery. 1995;118(5):904-906.
12. Noujaim HM, Mayer DA, Buckles JA, et al. Techniques for and outcome of liver transplantation in neonates and infants weighing up to 5 kilograms. J Pediatr Surg. 2002;37(2):159-164.
13. Schulze M, Dresske B, Deinzer J, et al. Implications for the usage of the left lateral liver graft for infants ≤ 10 kg, irrespective of a large-for-size situation - are monosegmental grafts redundant? Transpl Int. 2011;24(8):797-804.
14. Colombani PM, Cigarroa FG, Schwarz K, Wise B, Maley WE, Klein AS. Liver transplantation in infants younger than 1 year of age. Ann Surg. 1996;223(6):658-662.
15. Kasahara M, Fukuda A, Yokoyama S, et al. Living donor liver transplantation with hyperreduced left lateral segments. J Pediatr Surg. 2008;43(8):1575-1578.