Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down‐staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow‐up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06‐1.85; I2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060‐2.370; I2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down‐staging therapy versus no downstaging, and this showed a significant increase in 1‐year (two studies, RR, 1.11; 95% CI, 1.01‐1.23) and 5‐year (1 study, RR, 1.17; 95% CI, 1.03‐1.32) post‐LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (Hepatology 2018;67:381‐400).

中文翻译：

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等待肝移植的肝细胞癌患者的治疗：系统评价和荟萃分析

被列入肝移植 (LT) 的肝细胞癌 (HCC) 患者通常在等待名单上接受局部治疗 (LRT) 治疗，其目的是防止 HCC 进展或减少 HCC 的可测量疾病负担获得更高的分配优先权。我们旨在综合有关 LRT 在管理 LT 候补名单上的 HCC 患者中的有效性的证据。我们对 1996 年至 2016 年 4 月 25 日的多个数据库进行了全面搜索，以获取纳入等待 LT 并在 LT 前接受桥接或降期治疗的肝硬化成人的研究。治疗包括经导管动脉化疗栓塞、经动脉放射栓塞、消融和放疗。我们纳入了比较研究和非比较研究。没有确定随机对照试验。对于 T1 HCC 和等待 LT 的成年人，只有两项非随机比较研究，均具有高偏倚风险，报告了感兴趣的结果。在一个系列中，接受 LRT 的 T1 HCC 患者在 6 个月时全因退出率为 5.3%，而在另一个未接受 LRT 的 T1 HCC 患者系列中，中位随访退出率为 2.4年和 T2 HCC 进展率分别为 30% 和 88%。对于等待 LT 的 T2 HCC 成人，任何桥接疗法的移植均显示因进展而退出等待名单的风险无显着降低（相对风险 [RR]，0.32；95% 置信区间 [CI]，0.06-1.85；I2 = 0 %）和所有原因导致的候补名单辍学率（RR，0.38；95% CI，0.060-2.370；I2 = 85。7%) 与基于三项比较研究的无治疗相比。由于偏倚、不精确和不一致的高风险，证据的质量非常低。有 5 项比较研究报告了移植后存活率，10 项比较研究报告了移植后复发，并且在这两个终点中没有发现显着差异。对于最初接受 LRT 的 T3 期 HCC 成人，有三项研究报告了任何降期治疗与不降期的移植，这表明 1 年显着增加（两项研究，RR，1.11；95% CI， 1.01-1.23) 和 5 年（1 项研究，RR，1.17；95% CI，1.03-1.32）接受 LRT 的患者的 LT 后存活率。由于存在严重的偏倚风险和不精确性，证据质量非常低。结论：在列入 LT 的 HCC 患者中，使用 LRT 与改善候补名单和移植后结果的趋势不显着相关，尽管现有证据存在选择偏倚的高风险。（肝病学 2018 年；67：381-400）。