Splenectomy before adult liver transplantation: a retrospective study

In our study, the grafts for LT were from donation after cardiac death. No prisoners were included as donors. The protocol was approved by the Ethics Committee of the West China Hospital of Sichuan University West China Hospital. Written informed consent was obtained from all the recipients prior to their surgery, and all of donations were voluntary and altruistic in all cases, and were in accordance with the ethical guidelines of the Declaration of Helsinki.

SPSS 18.0 statistical software (SPSS Inc., Chicago, IL, USA) was used to analyse the relevant data. SPSS 18 did not have a stand-alone function for propensity score analysis, but after the R software and plug-in that could link with the corresponding versions of SPSS and propensity score matching package were installed, propensity score matching could be accomplished by SPSS software [16]. To minimize the influence of other confounders on outcome, we used a propensity score analysis to match Sp(+) patients with Sp(−) patients. Sp(+) patients was matched in a 1:1 ratio with Sp(−) patients using the nearest neighbor matching and based on the variables listed in Table 1. Categorical data were presented as number (per cent) and compared using Pearson chi-Square, Fisher’s exact test. Continuous variables were expressed as the mean value ± SD and analyzed using t-test and repeated measure analysis of variance. Overall patient survival was estimated by the Kaplan–Meier method, and differences between two groups were determined by log-rank test. Independent factors for the platelet count and overall survival were analyzed by multiple regression and Cox proportional hazards models, respectively. P < 0.05 was considered statistically significant.

At present, LT is the last choice for many patients with end-stage liver disease. The wait for transplantation is also long due to the shortage of donor organs. Moreover, LT is not feasible for all patients. Therefore, in order to reduce the pressure on the portal vein, many patients with liver disease choose to undergo splenectomy as a bridging therapy prior to LT. Thus, the influence of splenectomy on LT is still worthy of consideration.

First, the most emphasized risk conveyed by pre-transplantation splenectomy is sepsis. By viewing other relevant literature, on follow-up studies of patients who underwent splenectomy for cirrhosis, but never had a LT, A meta-analysis of follow-up studies involving 19,680 patients showed that the incidence of sepsis among adult splenectomy patients was low, and that a high mortality rate was observed only among children [17]. This meta-analysis thus suggested a low post-operative rate of sepsis after adult splenectomy. Moreover, this is the premise of a low post-operative infection rate in Sp(+) group. Furthermore, for patients who underwent splenectomy and LT synchronously, Samimi et al. [18] reported that synchronous splenectomy resulted in a higher mortality rate, mainly related to septic complications. However, for patients who underwent splenectomy before LT, Jeng et al. [19] and Shimadaet al. [20] found that the risk of infection after LT in patients who had undergone splenectomy remained unchanged. Our results confirm that for the patients who underwent splenectomy before LT (group Sp(+)),the risk of infection was not increased.

We further investigated the influence of splenectomy on post-operative complications after LT, based on the Clavien–Dindo complication classification [21]. 21 deaths occurred in the 90 days after operation in either the Sp(−) or Sp(+) group, and no difference existed between the two groups with regard to various grades of post-operative complications and 90 days mortality. Settmacher et al. [22] reported that concomitant splenectomy during LT was associated with a significant and increased risk of venous complications, such as portal vein thrombosis. However, none of our liver transplant patients in whom splenectomy was performed prior to LT developed portal vein thrombosis. This is consistent with the reports of Hirotaka et al. [7] It is interesting that the incidence of one of the post-operative complications of LT, thrombocytopenia, decreased rather than increased in patients who underwent splenectomy. Many studies have found that the platelet count reaches a nadir at days 2–5 post-transplant, but returned to preoperative levels by weeks 1–2 [23‐26]. The reason for this remains unclear. Chang et al. [27] have found that persistent thrombocytopenia is an indicator of a higher rate of fungal infections in liver transplant recipients. On the other hand, platelet-derived serotonin has been found to be important for liver regeneration [28]. A retrospective study [29] has shown that transfused platelets are significantly associated with graft regeneration in liver donors. Furthermore, Bleibel et al. [30] recently observed that peripheral platelet count correlated with liver atrophy and predicted long-term mortality in patients on the liver transplant waiting list. Interestingly, splenectomy can increase the number of platelets, yet portacaval or distal splenorenal shunts cannot increase the number of platelets [31‐33]. The reason for this may be that platelets participate in splenic destruction, rather than merely pooling in the spleen [34‐36]. In our series of 162 post-matched patients, post-operative peripheral platelet levels were significantly higher (P = 0.041) in group Sp(+) than in group Sp(−). Therefore, we believe that splenectomy is an effective approach for increasing platelets. Furthermore, EAD is often used as the best choice of the primary outcome after LT. Li et al. [37] have conducted a retrospective study on adult-to-adult living donor liver transplantation (A-A LDLT) and found that an immediate post-operative platelet count of less than 68 × 10⁹/L was an independent risk factor for post-operative EAD. Interestingly, in our study the Group Sp(−) did have more EAD than Sp(+) (P = 0.038). As for its reasons, we considered immediate postoperative low platelet mainly affected the recovery of the liver function by liver regeneration, because there was no significant difference between the two groups with regard to postoperative major complications. The results were also confirmed by us in the living donor liver transplantation [37]. But the specific mechanism still remained to be further studied in the laboratory.

We also compared the overall survival rate of patients between the Sp(−) and Sp(+) groups. In the past, there had been many reports on the effects of LT after splenectomy or simultaneous splenectomy in liver transplant patients, but due to the small number of observations, the results were controversial. At present, there is a lack of a corresponding standard for patients who underwent splenectomy prior to liver transplant. In order to verify the effects of splenectomy on liver transplant patients, we here observed 820 patients in a 5-yearfollow-up study. After analyzing the cumulative overall survival rates of groups Sp(+) and Sp(−), we found no significant differences in the 1-, 3-, and 5-year survival rates in the post-match model. Therefore, we concluded that LT may be suitable for the patients who underwent splenectomy. However, well-designed, long-term, randomized, controlled, prospective trials are still necessary to confirm this proposal.

Through the above analysis, pre-transplantation splenectomy is recommended in cases with risky PHT patients without appropriate source of liver for LT. But one thing to note is that as a “re-operation” the splenectomy is often associated with more difficult dissection due to adhesions. We subjectively believed the transplant operation was perhaps more difficult in the splenectomy group. Although the average time spent on Sp(−) was less than group Sp(+), there was no statistic difference between operative times and intraoperative blood loss. Finally, we believe that adhesion does have some effect on group Sp(+), but it is not obvious.

Our study has several limitations. First, we performed our analysis using only about 82 cases in the Sp(+) group. The limited number of patients may underlie the lack of significant differences and a larger multicenter study should investigate this matter further. Second, these data were retrospectively collected and analyzed, and a prospective clinical investigation should be performed to evaluate the role of splenectomy in this context.

The results of the present study suggest that pre-transplantation is a very effective method for the treatment of thrombocytopenia after ADLT. Moreover, compared with Sp(−), the risk of infection and post-operative complications in group Sp(+) is not increased, and group Sp(+) had a lower rate of post-operative EAD. There was no difference in the cumulative survival rates between the two groups. Pre-transplantation splenectomy is recommended in cases with risky PHT patients without appropriate source of liver for LT.