Chung William, Wong Kevin, Ravindranayagam Noel, Tang Lauren, Grace Josephine, Wong Darren, Con Danny, Sinclair Marie, Majumdar Avik, Kutaiba Numan, Hui Samuel, Gow Paul, Muralidharan Vijayaragavan, Dobrovic Alexander, Testro Adam
Department of Gastroenterology, Austin Health, Heidelberg 3084, Victoria, Australia.
Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia.
World J Transplant. 2024 Sep 18;14(3):94914. doi: 10.5500/wjt.v14.i3.94914.
Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.
To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT.
This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing.
Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes.
Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.
肝移植（LT）是肝细胞癌（HCC）患者一种潜在的治愈性疗法。LT后HCC复发与生存率降低相关。人们对化学预防以改善LT后HCC相关结局的兴趣日益增加。
研究使用具有化学预防特性的药物预防HCC是否有益，以及LT后患者的结局。
这是一项对2005年至2022年期间在澳大利亚一个中心接受已故供体LT治疗HCC的成年患者的回顾性研究。药物使用定义为LT后24个月内使用他汀类药物、阿司匹林或二甲双胍治疗≥29天。采用具有时间依赖性协变量的Cox比例风险模型进行生存分析。结局指标为HCC复发和全因死亡率的复合终点、HCC复发和HCC相关死亡率。进行敏感性分析以考虑永生时间偏倚和他汀类药物剂量。
本研究纳入305例患者，其中253例（82.95%）为男性，中位年龄58.90岁。肝病病因包括150例（49.18%）丙型肝炎、73例（23.93%）乙型肝炎（HBV）和33例（10.82%）非酒精性脂肪性肝病（NAFLD）。56例（18.36%）服用他汀类药物，51例（16.72%）服用阿司匹林，50例（16.39%）服用二甲双胍。在中位随访时间59.90个月期间，34例（11.15%）发生HCC复发，48例（15.74%）死亡，17例（5.57%）死于HCC相关死亡率。使用他汀类药物、阿司匹林或二甲双胍在HCC复发或全因死亡率的复合终点方面无统计学显著差异[风险比（HR）：1.16，95%置信区间（CI）：0.58 - 2.30；HR：1.21，95%CI：0.28 - 5.27；HR：0.61，95%CI：0.27 - 1.36]，在HCC复发方面（HR：0.52，95%CI：0.20 - 1.35；HR：0.51，95%CI：0.14 - 1.93；HR 1.00，95%CI：0.37 - 2.72），或在HCC相关死亡率方面（HR：0.32，95%CI：0.033 - 3.09；HR：0.71，95%CI：0.14 - 3.73；HR：1.57，95%CI：0.61 - 4.04）分别无统计学显著差异。他汀类药物剂量与HCC相关结局无统计学显著差异。
在澳大利亚NAFLD比例较低的大部分历史队列患者中，使用他汀类药物、二甲双胍或阿司匹林与LT后改善HCC相关结局无关。需要进一步的前瞻性、多中心研究来阐明这些药物改善HCC相关结局的任何潜在益处。
