Long-term administration of Tolvaptan to patients with decompensated cirrhosis

Abstract

Aim: Tolvaptan, an oral vasopressin-2 antagonist, sometimes improves hepatic edema including ascites in patients with decompensated cirrhosis. In this study, we examined the effectiveness and survival advantage in patients with the long-term administration of tolvaptan. Methods: A total of 115 patients with refractory ascites who were treated with tolvaptan were retrospectively analyzed based on their clinical records. Patients with a decrease in body weight of ≥1.5 kg from the baseline on day 7 were determined as responders. Re-exacerbation was defined as a return to the baseline BW, dose escalation of conventional diuretics, or abdominal drainage. Results: Of the 115 patients, 84 were included in this analysis. Response to tolvaptan treatment was observed in 55 out of the 84 patients (65.5%), with a mean weight reduction of 2.52 kg. Multivariate analyses demonstrated that body mass index (≥24) and urinary specific gravity (≥1.018) were significant predictors of the response to tolvaptan. However, cumulative re-exacerbation rates in responders at 6 and 12 months were 42.4 and 60.1%, respectively. Child-Pugh (classification C), HCC complication, and serum sodium levels (≥133 mEq/L) were determined as independent prognostic factors impacting overall survival (OS). Although there were no significant differences in OS between tolvaptan responders and non-responders, the responders without re-exacerbation within 3 months showed significantly longer OS than those with re-exacerbation within 3 months. Conclusion: A persistent therapeutic response, but not early response to tolvaptan, was associated with favorable survival of decompensated cirrhotic patients.

High expression of a vascular stricture‐related marker is predictive of an early response to tolvaptan, and a low fractional excretion of sodium is predictive of a poor long‐term survival after tolvaptan administration for liver cirrhosis

“…This difference, or other unknown factors, might affect the clinical course after tolvaptan administration. Several studies have shown no impact of the tolvaptan response on the survival, as in our present study 31,32 . Given that large‐scale studies have shown significance, we must include more patients in subsequent studies.…”

“…Several studies have shown no impact of the tolvaptan response on the survival, as in our present study. 31,32 Given that large-scale studies have shown significance, we must include more patients in subsequent studies.…”

Renal water transport in health and disease

“…However, post hoc analyses did identify the class of patients who had an improved outcome with tolvaptan [ 89 ]. In liver cirrhosis, tolvaptan may improve long-term survival if the therapeutic response is sustained in Japanese patients [ 38 ], but other studies did not observe this better outcome, and EASL does not recommend its use for long term [ 1 ], whereas the Japan Society of Hepatology is more in favor [ 94 ]. More studies are therefore needed to better delineate the long-term use of tolvaptan.…”

Management of Cirrhotic Ascites under the Add-on Administration of Tolvaptan

“…Several studies have shown that the administration of tolvaptan had no effect on survival [57,80,81]. These studies showed prognostic factors, such as complications with HCC and low fractional excretion of sodium (FENa) [57], complications with HCC and Child-…”

“…Several studies have shown that the administration of tolvaptan had no effect on survival [ 57 , 80 , 81 ]. These studies showed prognostic factors, such as complications with HCC and low fractional excretion of sodium (FENa) [ 57 ], complications with HCC and Child-Pugh class C [ 80 ], and a rapid and early decrease in a bioimpedance analysis (defined by intracellular water at 6 h after the first dose of tolvaptan) [ 81 ]. These factors are also convincing.…”