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Saudi Journal of Kidney Diseases and Transplantation
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Year : 1996  |  Volume : 7  |  Issue : 2  |  Page : 173-177
Liver Transplantation at King Fahad National Guard Hospital Riyadh, Kingdom of Saudi Arabia


Department of Hepatobiliary Sciences, King Fahad National Guard Hospital, Riyadh, Saudi Arabia

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   Abstract 

Liver disease is a major medical problem in the Kingdom of Saudi Arabia and is mostly due to viral hepatitis. Liver transplantation is the only option for patients with end-stage liver disease offering good long-term survival. The first liver transplant at the King Fahad National Guard Hospital was performed in February 1994 and since then, 40 liver transplants have been performed on 37 patients. Immunosuppression consisted of prednisone combined with cyclosporin (Neoral) or FK 506. Maintenance immunosuppression was with the use of cyclosporin or FK 506 as monotherapy. All, but one patient, survived the surgical procedure; there were no cases of primary non-function; acute cellular rejection occurred in 12 patients all of whom responded to steroids. Pneumonia and biliary sepsis occurred in 12 patients each. A total of 10 patients died, with sepsis being the leading cause of death. The overall graft survival was 73%. Donor shortage continues to be a major limiting factor.

Keywords: End-stage liver disease, Liver transplantation, Saudi Arabia.

How to cite this article:
Al Sebayel M, Kizilisik A T, Ramirez C, Altraif I, Hammad A, Littlejohn W, de Cordier M B, Geldhof G, Bhatti T J, Abdulla A. Liver Transplantation at King Fahad National Guard Hospital Riyadh, Kingdom of Saudi Arabia. Saudi J Kidney Dis Transpl 1996;7:173-7

How to cite this URL:
Al Sebayel M, Kizilisik A T, Ramirez C, Altraif I, Hammad A, Littlejohn W, de Cordier M B, Geldhof G, Bhatti T J, Abdulla A. Liver Transplantation at King Fahad National Guard Hospital Riyadh, Kingdom of Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 1996 [cited 2020 Sep 27];7:173-7. Available from: http://www.sjkdt.org/text.asp?1996/7/2/173/39522

   Introduction Top


Several hospital and community-based studies have shown a high incidence of liver disease in the Kingdom of Saudi Arabia (KSA), with viral hepatitis as the main causative factor(s) [1],[2] . Complications of advanced liver disease have been the subject of several publications confirming that liver disease is a major medical problem in KSA [3],[4],[5] . Although many therapeutic and preventive measures are beneficial in the initial management of liver diseases, liver transplantation remains the only option for patients with end-stage liver disease, offering long- term survival of as high as 80% [6] .

In Western countries, where the prevalence of liver disease is low, it is estimated that 5­15 patients per million population need liver transplantation each year [7],[8] . This figure can probably be multiplied several fold if applied to KSA, considering the high prevalence of liver disease in this country [12] We believe, based on experience in the Western countries and statistical figures from the Kingdom, that between 300-1000 patients need liver transplantation annually in KSA.

The first liver transplantation in KSA was performed at the Riyadh Armed Forces Hospital in June 1990. This was followed by a "quiet" period during which, only five liver transplants were performed [9] . How­ever, between February 1994 and February 1996, a total of 92 liver transplants have been performed on 85 patients in three hospitals in the Kingdom (personal communi­cation with the Saudi Center for Organ Transplantation; SCOT). The liver transplant program at the King Fahad National Guard Hospital was launched in January 1994 and the first liver transplant was performed on February 17, 1994; the patient is enjoying good health after more than two years post­transplant. Our experience over these two years will be briefly discussed with special emphasis on the problems unique to the Kingdom of Saudi Arabia.


   Patients and Methods Top


Between February 1994 and February 1996, a total of 40 liver transplants were performed on 37 patients in our institution. [Table - 1] details the sex and age of the study patients. A standard evaluation protocol was used for all patients, who were then presented to the liver transplant selection committee and placed on the national trans­plantation waiting list handled by SCOT. When a suitable donor became available, the transplant procedure was undertaken using the standard surgical technique [10] . Veno-venous bypass was omitted in four cases. Post-operative care was according to standard protocol. At the beginning of the program, the immunosuppression regimen consisted of cyclosporin, azathioprine and prednisone. Initially, cyclosporin was given intravenously (i.v.) during the first few days and then changed to the oral form. Sub­sequently, with the availability of FK 506, the patients were randomized to FK 506 or the new formulation of cyclosporin (Neoral). FK 506 was given at a dose of 0.05-0.1 mg/kg/day in conjunction with steroids in the form of methylprednisolone given in a bolus dose of 1 gm i.v. in the operating room, followed by a steroid taper as per protocol. This consisted of prednisone given at a dose of 100 mg/day tapered down to 20 mg/day over a few days which was then tapered down further and eventually stopped after three months. The new formulation of cyclosporin (Neoral) was given at a dose of 10-15 mg/kg/day with the same steroid regimen. The first dose of FK 506 or cyclosporin was given 12-24 hours post-transplant after ascertaining the renal function status of the patient. Following discharge from the hospital, allograft function and the immunosuppressive drug levels were monitored twice weekly for the first three months, once a week for the subsequent three months and from then onwards, on a less frequent basis. During the first three months, the trough cyclosporin level was kept at 350-450 ng/ml (TDX monoclonal assay). When FK 506 was used, the whole blood FK level was kept between 10-20 ng/ml for three months.

During the follow-up period, the patients were assessed clinically and by laboratory tests to ascertain the normal function of the graft. Rejection was diagnosed by liver biopsy and treated with steroids. Doppler ultrasound was employed when indicated, to check the vascularity of the graft. Invasive radiological and endoscopic studies such as percutaneous cholangiogram, endoscopic retrograde cholangio-pancreatography (ERCP) and angiography were performed to deli­neate the biliary system and hepatic artery whenever clinically indicated. Follow-up of the patients was made by the transplant team utilizing a very strict protocol.


   Results Top


[Table - 2] shows the etiology of end-stage liver disease in the 37 liver transplant patients. All patients survived the surgical procedure except for one, who died of intra­operative hemorrhagic shock. This patient was grossly coagulopathic with severe portal hypertension due to portal vein thrombosis. There were no cases of primary non-function, although, severe dysfunction (ALT > 3000 IU) occurred in nine grafts (23%), and moderate dysfunction (ALT 1500-3000 IU) occurred in 11 grafts (28%). Acute cellular rejection occurred in 12 patients (31%), all of whom responded to steroids. Chronic rejection occurred in one patient more than one year from initial transplant. She was successfully re­transplanted.

The most common infectious complication encountered was pneumonia which occurred in 12 patients (32%). Biliary sepsis, mani­festing as biliary leak following T-tube removal three months post-transplant, occurred in 12 out of 20 patients who had duct to duct anastomosis with T-tube. All cases were managed successfully by conservative measures except for one patient, who eventually died of sepsis. One patient developed a biliary leak in the immediate post-operative period following a Roux-en­Y anastomosis which was successfully managed surgically. Fungal sepsis (Candida) occurred in two patients and cytomegalo­virus infection in four. Hepatitis C recur­rence was high, 10/20 (50%)), with most of the cases following a benign course. There was no recurrence of hepatocellular carci­noma in the five patients with this original liver disease, with the longest follow-up in this group of patients being 20 months. Ten patients died between one week and three months after transplantation, mostly due to sepsis. [Table - 3] details the cause of death in each patient.


   Discussion Top


The success of any liver transplant program depends on detailed pre-operative evaluation of potential recipients, precise surgical technique and strict post-transplant follow-up. These factors contributed to the 73% survival rate achieved at the King Fahad National Guard Hospital Liver Transplant Program, which is comparable to the 76% one-year survival rate reported by United Network of Organ Sharing (UNOS), USA [6] . The mortality observed in our program was related to sepsis in 70% of the cases with very few technical compli­cations. The source of sepsis in most cases was hospital acquired, due partially, to confining transplant and non-transplant patients together in the same surgical/ medical intensive care unit. The incidence of infection was reduced dramatically when strict barrier isolation was employed for all post-transplant patients.

Primary non-function of the graft can occur in up to 25% of cases [11] . Although this was not seen in our program, moderate to severe graft dysfunction was seen in 20/40 transplants (50%). This is probably due to the relatively poor quality of the organs harvested. This is despite applying strict criteria for utilizing donor organs in KSA which resulted in the use of only 75% of the organs harvested. Such strict criteria, probably account for the fact that no primary non-function occurred in our study patients. Since the only option for patients with primary non-function is re-trans­plantation, this devastating complication means almost certain death for the patients in the face of organ shortage that exists in the Kingdom.

Acute rejection has been reported to occur in 50-90% of cases according to some series [12],[13] . Although our immunosup­pression regimen is relatively low (mono­therapy after three months), rejection occurred in only 31% of the cases. The finding of a low incidence of acute rejection in our series is encouraging when one con­siders the infectious, nephrotoxic and other complications related to immunosuppressive drug therapy. It indicates that our patients, for some unknown reasons, need lower doses of immunosuppressive medications.

Biliary complications are common following orthotopic liver transplantation and require re-operation in 10-20% of the cases according to some series [14] . In our program, only one patient developed a leak in the immediate post-operative period following a Roux-en-Y anastomosis. How­ever, removal of the T-tube three months after transplantation in patients with duct to duct anastomosis was complicated by biliary leak in 60% of the cases, causing significant morbidity and one mortality. This made us change our technique to duct anastomosis without a T-tube in the last 12 cases and we have not encountered any strictures or leaks since then.

Recurrence of hepatitis C is the rule, occurring in up to 95% of cases in some series [15] . In our program, recurrence occurred in only 50% of the patients as confirmed histologically and by polymerase chain reaction. However, longer follow-up of this group of patients may reveal more recurrences in the future. In most cases, hepatitis C that has recurred in the graft takes a benign course maintaining good allograft function for a long period of time without any specific treatment. Further­more, our preliminary data in using inter­feron and ribavirin in the treatment of post­liver transplant hepatitis C. recurrence has been disappointing (unpublished data).

In conclusion, the two years experience of the liver transplant program at King Fahad National Guard Hospital, has yielded results comparable to the well-established programs in North America and Europe. This is despite difficulties encountered in relation to donor availability, the sub-optimal condition of the organs harvested and other post­operative complications, particularly infection. Infectious complications were a major problem in the past, but have been reduced more recently, by adopting strict isolation measures and refinement of surgical technique.

In our opinion, with the current success achieved here and elsewhere, the need for liver transplantation will substantially exceed the supply of available organs in the coming years. Consequently, more efforts should be directed towards, not only donor promotion, but also improvement in donor management. Such goals could only be accomplished by direct co-operation between the donor hospitals, the transplant programs and the Saudi Center for Organ Transplantation.

 
   References Top

1.Al Faleh FZ. Hepatitis C infection in Saudi Arabia. Ann Saudi Med 1988;8:474­-80.  Back to cited text no. 1    
2.Arya SC. Viral Hepatitis in Saudi Arabia: what next during the 1990's? Saudi Med J 1989;10:267-71.  Back to cited text no. 2    
3.Shobokshi OA. The epidemiology of hepatitis B virus and primary hepatocellular carcinoma in Western Saudi Arabia.Ann Saudi Med 1988;8:81A.  Back to cited text no. 3    
4.Al-Karawi MA, Shariq S, El Sheikh Mohammed AR, Saeed AA, Ahmed AM. Hepatitis C Virus infection in chronic liver disease and hepatocellular carcinoma in Saudi Arabia. J Gastroenterol Hepatol 1992;7:237-9.  Back to cited text no. 4    
5.Noun MS, Bashi SA, Laajam MA, Mofleh IA, Al Aska A. Hepatitis B virus vs schistosomiasis and hepatocellular carcinoma in Saudi Arabia. East Afr Med J 1990; 67:139-45.  Back to cited text no. 5    
6.Uited Network of Organ Sharing (UNOS) and Department of Health and Human Services, U.S.A. 1994. Report of center specific graft and patient survival rate  Back to cited text no. 6    
7.Starzl TE, Iwatsuki S, Van Thiel DH, et al. Evolution of liver transplantation. Hepatology 1982;2:614-36.  Back to cited text no. 7    
8.Starzl TE, Demetris AJ, Van Thiel DH. Liver transplantation. New Engl J Med 1989;321:1014-22.  Back to cited text no. 8    
9.Shaheen FAM, Souqiyyeh MZ, Al­Swailem AR. Saudi Center for Organ Transplantation: activities and achievements. Saudi J Kidney Dis Transplant 1995;6:41-52.  Back to cited text no. 9    
10.Starzl TE, Demetris AJ. Liver transplantation: a 31 year perspective. Part I. Curr Probl Surg 1990;27:49-116.  Back to cited text no. 10    
11.Clavien PA, Harvey PR, Strasberg SM. Preservation of reperfusion injuries in liver allografts. An overview and synthesis of current studies. Transplantation 1992;53:957-78.  Back to cited text no. 11    
12.Busuttil RW, Colonna JO, Hiatt JR, et al. The first 100 liver transplants at UCLA. Ann Surg 1987;206:387-402.  Back to cited text no. 12    
13.Gouw AS, Snover DC, Grand J, et al. Acute rejection in human liver grafts: a comparative histologic study of cases maintained on azathioprine and prednisone versus cyclosporine A and low dose steroids. Hum Pathol 1988;19:1036-42.  Back to cited text no. 13    
14.Lerut J, Gordon RD, Iwatsuki S, et al. Biliary tract complications in human orthotopic liver. Transplantation 1987;43:47-51.  Back to cited text no. 14    
15.Wright TL, Donregan E, Hsu HH, et al. Recurrent and acquired hepatitis viral infection in liver transplant recipients. Gastroenterol 1992;103:317- 22.  Back to cited text no. 15    

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Correspondence Address:
M Al Sebayel
Department of Hepatobiliary Sciences, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426
Saudi Arabia
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PMID: 18417935

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    Abstract
    Introduction
    Patients and Methods
    Results
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    References
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