Liver Transplantation: Experience at King Hussein Medical Center, Jordan

ABSTRACT

Objective: To review the experience and outcome of liver transplantation recipients at King Hussein Medical Center.

Methods: We retrospectively analyzed the results of 67 liver transplantations; 65 living-related donor liver transplantations for 64 recipients and two cadaveric donor liver transplantation at King Hussein Medical Center between June 2004 and December 2011. The grafts were: 60 right liver lobes, four left liver lobes, one hepatic segments II and III and two whole livers (cadaveric). All living donors were closely related to the recipients except for the cadavers. Data were obtained by a specially designed medical record abstract form. Of the 67 liver transplantations, the first 42, were performed under the supervision of the Turkish liver transplantation team. Six recipients had concomitant hepatocellular carcinoma and liver cirrhosis. Retransplantation was performed for one recipient. Simple descriptive statistical methods (frequency, mean and percentage) were used to describe the study variables.

Results:  Total mortality rate was 11 (17%). The causes of death were sepsis in four patients, hepatic arterial thromboses in three patients, small-for-size in one patient, and porto-pulmonary hypertension in one patient. Morbidity rate was 49 (73.1 %). The main causes of morbidity were biliary leaks in 13 patients, biliary stricture in nine patients, recurrence of primary disease in nine patients acute rejection in five patients, wound infection in four patients, and bile duct stones in one patient.  The follow-up period ranged between one month to 90 months (average 45.5 months). One and three year survival rates were 80% and 70.2% respectively. However, most complications have been treated with interventional techniques.  All living donors are alive in a good health and returned to their normal life.

Conclusions: In view of critical shortage of cadaveric donor liver transplantation, living-donor liver transplantation is an opportune option for patients with decompensated liver disease in Jordan. Our patients’ outcome is improving with time and this could be attributed to gaining more experience and by-passing the learning curve by the liver transplantation team in our center.  

Key words: Complications, Liver transplantation, Outcome

JRMS December 2012; 19(4): 5-12

Introduction

Liver transplantation is the therapeutic option of choice for acute and chronic end-stage liver disease. Transplantation is a relatively new medical specialty, dating back to only 1954 when Dr Joseph Murray did the first living donor kidney transplantation, then followed by cadaveric donation after eight years.⁽¹⁾

Table I. Patients characteristics of the study group

Table II. Indications for liver transplantation among the study group

AIH: Autoimmune Hepatitis            HBV: Hepatitis B Virus             HCV: Hepatitis C Virus       HCC: Hepatocellular Carcinoma

Thomas Starzl performed the first three cadaveric human liver transplantations in 1963, all died before reaching 1-year survival, and it was not until 1967 when he did the first successful transplantation.^(2-4) The first attempt of  Living Donor Liver Transplantation (LDLT) was in children and was performed by Raia et al. in 1988, while  the first successful LDLT in an adult recipient was done for the first time  by the  Japanese  in 1994  and then Western countries has followed this path.^(5,6) While the shortage of donor organs is a global problem, the situation appears more critical in Asia where cadaveric organ donation remains below five per million populations (pmp).⁽⁷⁾

Although LDLT has several advantages over cadaveric liver donor transplantation (CDLT), the main limitation for successful adult-to adult LDLT is Graft-Recipient weight-Ratio (G-RW-R) mismatch, in which the graft cannot meet the metabolic demands of the recipients.^(8,9) It is obvious that adults need larger graft to meet their metabolic demand.  So, left or right hepatectomies were required, which put the donor at the risk of high morbidity from a significantly major operation.^(6,10,11)

The aim of this study is to review our experience and outcome of liver transplantation recipients, at King Hussein Medical Center.

Methods

Between June 2004 and December 2011, a total of 67 liver transplantations were performed for 66 recipients. Sixty five of them were LDLTs including one re-transplantation while the other two were CDLT.  Male to female ratio was 49\18 (73%-27%). Fifty eight percent of the patients were adults with the average age of 40 years (range 17-63 years), while the remaining recipients were children (less than 15 years of age) with the average age of nine (range 3-14 years).  Recipient characteristics are showed in Table I.

Most of the indications for liver transplantation were chronic liver cirrhosis due to cryptogenic hepatitis (14), viral hepatitis (15), cholestatic liver disease (6), autoimmune hepatitis (AIH) (8), and other factors (Table II).

The pre-transplant condition of the recipients was evaluated by the modified model for end- stage  liver  disease (MELD) score⁽¹²⁾ which  has been documented to be reliable in predicting the prognosis of the patients. The contraindications for transplantation are listed in Table III. 

Table III. Contraindication for liver transplantation

We accepted only donors with graft-to-recipient weight ratios ≥ 0.8% and fatty liver ≤ 20%. The remnant of donor’s liver (residual liver volume) always exceeded 35% of the total liver volume as calculated by computed tomography volumetry. The age of the donors ranged from 19 to 55 years (average 37 years).  Simple descriptive statistical methods (frequency, mean and percentage) were used to describe the study variables.

Donor hepatectomy:

Donor hepatectomy is a standard procedure in all centers.

Three  hepatectomies  were  defined according to the segmental anatomy of Couinaud. Left Lateral Hepatectomy (LL) for resection of segments II and III, left hepatectomy (LH) for segments resection of  II, III and IV, and right hepatectomy (RH) for  segments V, VI, VII and VIII resection⁽¹³⁾  (see Fig.1).

Recipient operation:

Total hepatectomy performed with the original hepatic veins (with extension to IVC to make triangular shape opening) or vena cava were used for the hepatic vein anastomosis. Biliary, portal and hepatic anastomosis were performed with loop magnification, and the arterial anastomosis performed by a micro-vascular surgeon with microscope. The hepatic veins anastomosed  to  IVC  with  continuous suture by Prolene  4\0,  also the portal veins (right and left) were anastomosed to the main portal vein by Prolene 5\0. Inferior hepatic veins (larger than 7mm) were anastomosed end to side to the inferior vena cava. After completion of the portal vein anastomosis, removal of the air and stagnant preservative solution from the graft done by washing out with the portal blood. The hepatic artery was anastomosed to the recipient right hepatic artery in the RH LDLTs except for two recipients; we used the splenic artery because of extensive intimal dissection in the hepatic artery which extended to the celiac trunck (Fig. 2), and to the left hepatic artery in the LT, LL LDLTS. In the CDLTs the common hepatic artery of the graft anastomosed to common hepatic artery of the recipient.

Biliary reconstruction was done with a duct-to-duct anastomosis in 60 transplants and with Roux-en-Y hepaticojejunostomy in seven transplants. Twenty eight (41%) of the 67 liver grafts had two bile ducts (Fig. 3). In five of these 28 grafts with two bile ducts, two separate anastomoses were performed. In the remaining 23 grafts, ductoplasty performed by approximating the neighboring bile duct and, sutured together to create a single bile duct opening. One of the 67 liver grafts had three bile ducts. In this situation, two neighboring ducts were sutured together and anastomosed end-to-side to the jejunum, and the third duct anastomosed separately end-to-side to the jejunum (Roux-en-Y hepaticojejunostomy). In this recipient, we placed internal catheters. In three recipients, a straight feeding tube was inserted from the common bile duct to the anastomotic site to enable external bile drainage.

Cell-saver was used during the recipient operation for 13 patients. Standard antibiotic therapy with gram-negative and gram-positive coverage was administered for five postoperative days. Lamivudine, 100 mg daily, was given orally for patients with hepatitis B viral infection before transplantation and continued long life afterward.  Hepatitis B immunoglobulin was used in all patient with hepatitis B at the anhepatic phase at a starting  dose of  2000iu and  then 500iu per day for one week ,then discontinued  when HBVAb titer (>100).

Immunosuppression induction therapy was provided with Methyl prednisolone 100mg intraoperatively and on postoperative day one then tapering daily till the day nine to be 20mg prednisolone orally. The postoperative immunosuppression was based on tacrolimus and mycophenolate mofetil and steroids. All recipients also received oral fluconazole 200mg daily after the operation for three months.

Results

Of the liver transplant recipients in our study, two underwent CDLT and sixty five underwent LDLT (60 underwent right lobe transplantation; four left lobe; and one transplantation of the left lateral segment). In one recipient, retransplantation was performed (8 days after the first transplantation) because of hepatic artery thrombosis. The mean ratio of graft volume to the  body  mass  of the recipients was 1% (range,0.8 –1.4) in the adult group and 3% (range, 2.6- 3.4) in the pediatric group. The average cold ischemia time of the liver graft was 75 minutes (range, 60-90 minutes). The average operative time was 12 hours (range, 8–16 hours). All except two recipients received blood transfusion (9 U; range 0-18 U). The average postoperative intensive care unit stay was 17.5 days (range, 10-25 days), and the average postoperative hospital stay was 37 days (range, 13-61 days).

Hepatic arterial thrombosis (HAT) has complicated three of our recipients (5.9%) in the early post operative days. This complication was diagnosed during routine liver enzymes test then proved by Doppler ultrasonographic examinations and CT angiogram. One of those three required retransplantation to treat his HAT, but died 24 hours after the operation. Thrombectomy was performed in one recipient, by interventional radiologist, but failed and the patient died. The third one died before any intervention because he developed multi-organ failure.

Two recipients developed bleeding one day after transplantation, which necessitated reopening. One was found to bleed from a branch of the hepatic artery and was successfully treated by ligation of the bleeding vessel, and the other one from the site of jejuno-jejunostomy and was treated by revision of the anastomosis.

Thirteen (19.4%) and nine (13.4%), of the 67 recipients in our study experienced a bile leak and bile duct stenosis respectively, and one of the stenosis  group had CBD stones. The bile leak occurred at the anastomotic site in eleven recipients, and from the graft cut surface in two recipients. Anastomotic bile leaks were treated by percutaneous drainage followed by endoscopic placement of a 7-10Fr plastic stent except two, where ductal anastomosis were completely disrupted and converted to roux-en-Y hepatico- jejenostomy. The non-anastomotic bile leaks were treated with percutaneous drainage. Bile duct stenoses occurred at the anastomotic site in seven recipients and at the nonanastomotic site in the remaining two recipients. All bile duct stenoses were treated with internal stent in our hepatology unit by ERCP with excellent results (Fig. 4), except for one that necessitated PTC by interventional radiologist and ERCP with extraction of stones from the CBD and insertion a stent (Fig. 5).

One hepatic vein stenosis, developed during the late  postoperative  period  which were treated by percutaneous transluminal angioplasty.

Table IV: Complications of the recipients and the management

 H-J: hepaticojejunostomy