Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

Abstract

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT £ 75 3 10 9 /L were matched with 97 of 119 patients who had preoperative PLT >75 3 10 9 /L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 3 10 9 /L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR] 5 3.09; 95% confidence interval [CI], 1.86-5.14; P < 0.001) and multivariate analyses (HR 5 2.10; 95% CI, 1.23-3.60; P 5 0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR 5 2.33; 95% CI, 1.36-4.01; P 5 0.002) and multivariate analyses (HR 5 1.90; 95% CI, 1.02-3.54; P 5 0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-tolymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation.Liver Transplantation 24 44-55 2018 AASLD. Liver transplantation is a well-established therapeutic option for treatment of hepatocellular carcinoma (HCC), addressing both underlying liver disease, which is considered a premalignant lesion, and tumor burden. However, many recipients experience tumor recurrence and recurrent HCC is a major cause of death. Thus, better understanding of the contributing factors for HCC metastasis will help improve liver transplant outcome. (1,2) The platelet is the primary cell for hemostasis and tissue repair, (3) but extensive experimental evidence has also illuminated the involvement of platelets in tumor growth and metastasis. (4)(5)(6) Clinical evidence has demonstrated an association between higher platelet counts (PLTs) and shorter survival time and increased recurrence after treatment in various solid tumors. (7) In terms of HCC, a retrospective analysis using a large database of biopsy-proven HCC patients reported a positive Abbrevi...

Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma

“…Platelets may also promote formation of metastasis [14]. In line with this, recent clinical data showed a correlation of elevated thrombocyte counts and worse prognosis in several cancer entities [15][16][17][18] as well as an increased risk of distant metastasis [19,20] and recurrence of disease after liver transplantation [21] in patients with HCC. Prophylactic treatment with daily acetylsalicylic acid significantly reduced the risk of adenocarcinoma development [22].…”

Living or deceased organ donors in liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis

“…14,15 Second, all available grafts were split livers for LDLT, in the process of rapid regeneration of a partial graft after LT, the released growth factors and cytokines might promote tumor progression and recurrence. 23,[53][54][55] Third, the surgical technique of LDLT does not comply with the principles of oncologic surgery. During LDLT, the native inferior vena cava, the longer bile duct, hepatic artery and portal vein would be preserved to match the volume-limited split liver, leading to possible tumor remnants.…”

Longer storage of red blood cells does not affect mortality in transfused liver transplant recipients

“…Graft failure was defined as death or retransplantation. In terms of HCC recurrence, survival analysis was performed using the Fine and Gray model, instead of the Cox model, to account for the competing risk of HCC‐unrelated death because HCC‐unrelated death significantly affects HCC recurrence probability in liver transplant recipients …”

“…In terms of HCC recurrence, survival analysis was performed using the Fine and Gray model, instead of the Cox model, to account for the competing risk of HCC-unrelated death because HCCunrelated death significantly affects HCC recurrence probability in liver transplant recipients. 21,24 Posttransplant complications were graded based on the modified Clavien-Dindo classification. 25 The degree of graft regeneration was calculated from the graft volume derived from computed tomography and graft weight directly measured after the graft was procured.…”