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Therapeutic efficacy of lenvatinib in hepatocellular carcinoma patients with portal hypertension.

Lenvatinib 治疗肝细胞癌合并门静脉高压患者的疗效。

  • 影响因子:3.11
  • DOI:10.1111/hepr.13537
  • 作者列表:"Maesaka K","Sakamori R","Yamada R","Urabe A","Tahata Y","Oshita M","Ohkawa K","Mita E","Hagiwara H","Tamura S","Ito T","Yakushijin T","Iio S","Kodama T","Hikita H","Tatsumi T","Takehara T
  • 发表时间:2020-06-19
Abstract

BACKGROUND AND AIM:Preserved liver function may be an important factor affecting therapeutic efficacy in hepatocellular carcinoma (HCC) patients treated with lenvatinib, but not all patients can be treated while preserving liver function. This study evaluated the therapeutic efficacy of lenvatinib in patients with poor liver function with and without portal hypertension. METHODS:This prospectively registered multicenter study analyzed 93 patients treated with lenvatinib. Progression-free survival (PFS) was compared between patients with and without advanced portal hypertension according to baseline liver function. Advanced portal hypertension was defined as having both splenomegaly and any portosystemic collaterals. RESULTS:Thirty-seven patients (40.7%) had advanced portal hypertension. PFS did not differ between patients with and without advanced portal hypertension in the entire cohort (median, 7.6 vs 4.1 months, respectively; p = 0.148) but was significantly longer in patients with advanced portal hypertension than in those without advanced portal hypertension in the albumin-bilirubin (ALBI) grade 2 or 3 group (median, 7.6 vs 2.1 months, respectively; p = 0.016). In a multivariate analysis, the presence of advanced portal hypertension was identified as the only significant predictor associated with prolonged PFS in the ALBI grade 2 or 3 group. CONCLUSIONS:Advanced portal hypertension was associated with the therapeutic efficacy of lenvatinib in controlling the progression of HCC in patients with poor liver function.

摘要

背景与目的: 在接受 lenvatinib 治疗的肝细胞癌 (HCC) 患者中,保留肝功能可能是影响疗效的重要因素,但并非所有患者都能在保留肝功能的同时进行治疗。本研究评价了 lenvatinib 治疗肝功能差伴或不伴门静脉高压患者的疗效。 方法: 这项前瞻性注册的多中心研究分析了 93 例接受 lenvatinib 治疗的患者。根据基线肝功能比较晚期门静脉高压症和非晚期门静脉高压症患者的无进展生存期 (PFS)。晚期门静脉高压症定义为脾肿大和任何门体侧支循环。 结果: 37 例 (40.7%) 患者有晚期门静脉高压症。在整个队列中,晚期门静脉高压和非晚期门静脉高压患者的 PFS 没有差异 (中位数分别为 7.6 个月 vs 4.1 个月; p = 0.148) 但在白蛋白-胆红素 (ALBI) 2 级或 3 级组中,晚期门静脉高压症患者明显长于无晚期门静脉高压症患者(中位数分别为 7.6 个月 vs 2.1 个月; p = 0.016)。在多变量分析中,在 ALBI 2 级或 3 级组中,晚期门静脉高压的存在被确定为与 PFS 延长相关的唯一显著预测因子。 结论: 晚期门静脉高压症与 lenvatinib 控制肝功能不良患者 HCC 进展的疗效相关。

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翻译标题与摘要 下载文献
影响因子:3.87
发表时间:2020-02-01
DOI:10.1111/liv.14321
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

翻译标题与摘要 下载文献
影响因子:2.57
发表时间:2020-02-01
DOI:10.1111/eci.13198
作者列表:["Li H","Wieser A","Zhang J","Liss I","Markwardt D","Hornung R","Neumann-Cip AC","Mayerle J","Gerbes A","Steib CJ"]

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