Published online Oct 7, 2019. doi: 10.3748/wjg.v25.i37.5630
Peer-review started: June 17, 2019
First decision: July 21, 2019
Revised: August 22, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: October 7, 2019
Processing time: 108 Days and 11 Hours
Tumor recurrence after orthotopic liver transplantation (OLT) is the stumbling block for long-term survival of the recipients with hepatocellular carcinoma (HCC). Identification of factors or measurements that have influence on overcoming HCC recurrence after OLT is of particular importance to innovate effective treatment strategy. Previous literature demonstrated that postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection (PTI), a common complication after OLT, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence and prolongs the long-term survival of transplant HCC patients needs to be clarified.
The management of tumor recurrence in transplant HCC patients remains challenging. The results of the present study indicated new insights regarding how to improve outcome of transplant HCC patients, especially those at a high risk for post-OLT death and tumor recurrence.
To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT.
A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group (53 patients) and a non-PTI group (185 patients). Univariate analyses, including the differences of overall survival (OS), recurrence-free survival (RFS), and post-recurrence survival (PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method, and the differences were compared using the log rank test. The variables with a P-value < 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model.
The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%, and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group (96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group (84.0%, 63.4%, and 60.2%) (P = 0.033). Absence of PTI was an independent risk factor for dismal OS (RR = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS (RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS (P = 0.003) and RFS (P = 0.003) rates of HCC patients with vascular invasion (IV), but did not impact on OS (P = 0.404) and RFS (P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, the patients with PTI showed significantly better OS (P = 0.026) and PRS (P = 0.042) rates than those without PTI.
PTI improves OS and RFS of transplant HCC patients at a high risk for post-transplant death and tumor recurrence, which may be attributed to suppressive effect of PTI on HCC recurrence.
Future development of bioengineered organisms that could potently activate the innate and adaptive immune system targeting tumor cells may present an attractive strategy to suppress HCC progression and prolong the patient survival after OLT with minimum side effects. Nevertheless, further validity of PTI as a potent tumor suppressor for HCC patients is critically needed in prospective cohorts at other transplant centers, as well as in well-designed experimental animal models.