Transplantation Proceedings
Volume 34, Issue 1, February 2002, Pages 290-291

Recipient factors analysis in long-term allograft survival of liver transplantation

M. Muro, F. Sánchez-Bueno, R. Robles, M. Miras, P. Ramirez and P. Parrilla

^a Immunology Service (M. Mu.), University Hospital "Virgen de la Arrixaca" Murcia, Spain
^b Digestive Medicine Service (M. Mi.), University Hospital "Virgen de la Arrixaca" Murcia, Spain
^c Liver Transplant Unit (F.S-B., R.R., P.R., P.P.), University Hospital "Virgen de la Arrixaca" Murcia, Spain

Liver allograft survival can be influenced by several factors that could participate in transplant outcome, independently of other elements such as HLA matching. Indeed, influences on transplant outcomes are complex: the role of a single factor can be confounded by many considerations other than immunosuppression. Therefore, not all recipients should be considered to be at equal risk at the time of liver transplant. Additional risk factors have been reported in several studies, including transplantation for primary sclerosing cholangitis,[1] for autoimmune diseases such as primary biliary cirrhosis, [2] for certain patterns of HLA mismatch between donor and recipient, [3, 4, 5 and 6] accompanied by cytomegalovirus infection, [7] between donor and recipient of different ethnic origins, [8] in the absence of azathioprine in the immunosuppressive regimen, [9] based on donor age and gender, [10 and 11] and in retransplants. [12]

The aim of this study was the retrospective investigation of the effect of recipient factors that influence the morbidity of and allograft survival in liver recipients.

Patients and methods

The study comprises a total of 200 consecutive orthotopic liver transplants (OLT), performed at the University Hospital "Virgen de la Arrixaca" in Murcia, Spain, who survived for more than 7 days after surgery. Retransplants (n=24), patients who died (n=9), and those undergoing graft loss (n=5) in the first week after OLT were excluded. OLTs with unknown data with respect to the analyzed factors as well as one case performed across ABO incompatibility, which was the only instance of hyperacute rejection in our series, were also excluded. The primary indications for liver transplant in patients are summarized in Table 1.

Table 1. Indication for Liver Transplantation in 149 Primary Transplant Recipients

OLT, orthotopic liver transplant.

The surgical procedure was performed following standard techniques: biliary reconstruction was accomplished by choledochocholedochostomy in all but two patients who had sclerosing cholangitis. Triple immunosuppressive therapy (methylprednisolone, azathioprine, and cyclosporine A) was used with all patients, and cyclosporine (CsA) was administered to achieve a 200 to 350 ng/mL serum level. An additional group was treated with OKT3 (Orthoclone; Ortho Pharmaceuticals, Raritan, NJ) during the first 14 days postransplant and CsA was added at day 7. The acute rejection diagnosis was based on conventional clinical, biochemical, and histologic criteria as previously published.[13 and 14] Acute rejection episodes treated with high doses of methylprednisolone (bolus of 500 mg) for 3 to 5 days, reversed the process in 92% of cases. The residual steroid-resistant cases were treated with OKT3. The chronic rejection diagnosis was based on histologic findings of disappearing interlobular bile ducts with scant mononuclear portal infiltrates, progressing later to bridging fibrosis with large, expanded portal tracts. Patients whose rejection persisted received retransplantation or rescue therapy with the immunosuppressant FK506.

Data were collected on the Access program (Microsoft). The correlation of various factors such as recipient age, sex, primary indication for liver transplantation, immunosuppressive therapy, infections, and acute rejection episodes, with outcome of 149 liver transplants with a follow-up of at least 5 years was investigated using SSPS (10.0) (SPSS, Chicago, Ill). Survival function estimates were computed using the Kaplan-Meier method, and comparisons between cumulative survival curves were performed using the generalized Wilcoxon test.

Results and discussion

The survival of 149 OLTs with complete data was investigated and correlated with different recipient factors such as recipient age, sex, primary indication for liver transplant, immunosuppressive therapy, presence of viral infections and occurrence of acute rejection episodes. The primary indications for liver transplant lead to differential outcomes: recipients with fulminant hepatitis as a cause of liver failure showed reduced survival rates in contrast to other recipients (33% v 59%, P = .047) (Fig 1A). Although primary sclerosing cholangitis and primary biliary cirrhosis[1 and 2] have also been reported as risk factors in liver transplantation, we did not identify this factor due to its low frequency in our recipients. The different immunosuppressive regimens did not seem to influence allograft survival (61% CsA vs. 51% CsA+OKT3, P = .59). Neither did recipient gender appear to play a role on survival (59% female vs. 57% male, P = .84). With respect to recipient age, 40 to 50 year age group showed the lowest survival (49%), followed by the 50 to 60 year (52%) and the over 60 year groups (61%). The highest survival was observed among recipients of 30 to 40, 0 to 20, and 20 to 30 years (76%, 73%, and 70%, respectively), but the differences were not statistically significant (P = .42) (Fig 1B), probably because the large number of groups masked the actual role that could be discovered in a layer series. The presence of viral infection (VHB, VHC, CMV) itself did not seem to significantly influence survival rates (54% infection vs 63% noninfection, P = .78), although it can be important in relation to partial HLA class I matching as a cause to trigger acute rejection such as we have recently described.[13] Additionally, in our series the occurrence of all acute rejection episodes did not clearly predispose to a reduced long-term allograft survival rate (58% nonacute rejection vs 57% acute rejection, P = .79), even if recipient morbidity was seriously affected.

Fig 1. The actuarial graft survival rates of 149 OLT recipients with different recipient factors. (a) Fulminant hepatitis (primary indication for liver transplant), the difference in graft survival curves between the Y curve (fulminant hepatitis) vs the N curve (nonfulminant hepatitis) was slighty significant (P = .047). (b) Recipient age (yrs: years).

In conclusion, these data indicate that recipient factors such as the presence of fulminant hepatitis and possibly age may determine graft outcome.

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