Hiramine Yasunari, Uto Hirofumi, Imamura Yasushi, Hiwaki Takuya, Kure Takeshi, Ijuin Sho, Oda Kohei, Mawatari Seiichi, Kumagai Kotaro, Tokunaga Koki, Higashi Hirofumi, Kanetsuki Ichiro, Kubozono Osamu, Maenohara Shigeho, Ido Akio
Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan.
Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan.
Hepatol Res. 2017 May;47(6):542-557. doi: 10.1111/hepr.12778. Epub 2016 Aug 30.
Tolvaptan, an oral active vasopressin V2 receptor antagonist, is widely used for hepatic edema in Japan, but its clinical benefits have yet to be fully clarified. The present study evaluated the efficacy of tolvaptan in hepatic edema.
The efficacy and treatment regimen of tolvaptan were evaluated in 150 patients with hepatic edema by analyzing the initial (day 14) and long-term (day 90) responses to the drug and their predictive factors. All patients were divided into good (Child-Pugh classification B, and absent of advanced hepatocellular carcinoma) and poor hepatic condition groups, and the response rates were compared between the two groups.
The initial response rate was 62%, and the long-term response rate was 47%. The assessment of predictive factors for response to tolvaptan showed that serum creatinine and C-reactive protein levels were important predictors of initial response, and that hepatic conditions, such as the Child-Pugh score or presence of hepatocellular carcinoma, as well as initial response, were significant predictors of long-term response. In addition, both the initial and long-term response rates and the cumulative survival rate were found to be higher in the good hepatic condition group than in the poor hepatic condition group, respectively (71% vs. 57%, P = 0.113; 62% vs. 39%, P = 0.009; log-rank test, P < 0.001).
These results suggest that tolvaptan may provide high response rates when used early in the course of hepatic edema, or when both hepatic and renal functions are still retained, leading to an improved disease prognosis.
托伐普坦是一种口服活性血管加压素V2受体拮抗剂，在日本广泛用于治疗肝性水肿，但其临床益处尚未完全明确。本研究评估了托伐普坦治疗肝性水肿的疗效。
通过分析150例肝性水肿患者对该药的初始（第14天）和长期（第90天）反应及其预测因素，评估托伐普坦的疗效和治疗方案。所有患者分为肝功能良好组（Child-Pugh分级为B级，无晚期肝细胞癌）和肝功能较差组，比较两组的反应率。
初始反应率为62%，长期反应率为47%。对托伐普坦反应的预测因素评估显示，血清肌酐和C反应蛋白水平是初始反应的重要预测指标，而肝功能状况，如Child-Pugh评分或肝细胞癌的存在，以及初始反应，是长期反应的重要预测指标。此外，肝功能良好组的初始和长期反应率及累积生存率均分别高于肝功能较差组（71%对57%，P = 0.113；62%对39%，P = 0.009；对数秩检验，P < 0.001）。
这些结果表明，托伐普坦在肝性水肿病程早期或肝肾功能仍保留时使用，可能会有较高的反应率，从而改善疾病预后。
