纤维化是否影响肝移植术后患者的生存：来自SEER数据库的证据

Does Fibrosis Influence Survival after Liver Transplantation? Evidence from the SEER Database

摘要: 背景与目的：肝纤维化是否与肝细胞癌(HCC)有关，并对HCC患者肝移植术后生存有影响？这个问题仍存在争议。本研究旨在通过(SEER)数据库对肝纤维化的严重程度是否影响HCC患者肝移植术后总生存期(OS)的问题进行探索。方法：从SEER数据库中入组了2004年至2016年间共计1536例HCC患者。首先，对肝纤维化患者进行倾向评分匹配(propensity score matching, PSM)，然后通过使用Kaplan-Meier和Cox比例风险回归模型确定纤维化组的风险比(HR)及95%置信区间(CI)，比较纤维化和其他临床病理特征对生存结局的影响。同时通过建立基于多变量分析得出的列线图，校准、检验、预测其准确性。结果：纤维化评分高(5~6分)的患者比例大于纤维化评分低(0~4分)的患者(89.2% vs. 10.8%)。通过多变量Cox比例风险模型，纤维化评分是OS的独立预后因素[风险比(HR)：1.461，95%置信区间(CI)：1.191~1.792，P < 0.001]，且与其他肿瘤特征相比，纤维化与生存结局的相关性较高。将诊断年龄、纤维化评分、性别、种族、美国联合癌症委员会(AJCC) T分期、N分期、肿瘤大小、病理分级和甲胎蛋白(AFP)水平纳入多因素分析。综合这些因素的列线图对HCC患者的预后预测(C指数：0.601，95% CI：0.569~0.632)。结论：纤维化增加是HCC肝移植术后患者生存的独立危险因素。

Abstract: Background and Purpose: Whether liver fibrosis is associated with hepatocellular carcinoma (HCC) affects patients’ survival after liver transplantation (LT) remains controversial. Using the US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, we explored whether the severity of liver fibrosis affected the overall survival (OS) after LT in patients with HCC. Methods: A total of 1536 HCC patients from the SEER database between 2004 and 2016 were enrolled. Propensity score matching was performed on patients with liver fibrosis. We then used Kaplan-Meier and Cox proportional hazards regression models to compare the effects of fibrosis and other clinicopathological characteristics on survival outcomes. We simultaneously established a nomogram based on multivariate analysis and then calibrated, tested, and predicted its accuracy. Results: The proportion of patients with a high fibrosis score (5~6 points, 89.2%) was greater than that of patients with a low fibrosis score (0~4 points, 10.8%). The fibrosis score was an independent prognostic factor for OS by a multivariate Cox proportional hazards model (hazard ratio [HR] 1.461, 95% confidence interval [CI] 1.191~1.792, P < 0.001) and was associated with a higher survival outcome than other tumor characteristics. Age at diagnosis, fibrosis score, gender, ethnicity, American Joint Cancer Committee tumor-node-metastasis stage, tumor size, case grade, and alpha-fetoprotein level were included in the multivariate analysis. A nomogram combining these factors predicted HCC patients’ prognoses (C-index 0.601, 95% CI 0.569~0.632). Conclusion: Increased fibrosis was an independent risk factor for survival in patients with HCC after LT, as analyzed by prognostic nomograms that included fibrosis scores and other risk factors.