Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)

Abstract

Background This large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes. Methods A prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs). Results Case reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was -2.6 ± 2.7 kg on day 7 and -3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of C 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/ dL) was the predictive factor for tolvaptan treatment response.Conclusions The results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.

Daily Monitoring of Serum <i>Wisteria floribunda</i> Agglutinin-Positive Mac-2 Binding Protein Is Useful for Predicting Therapeutic Effect of Tolvaptan in Cirrhotic Ascites

“…As shown in Table 2, there was no significant difference in the effect of TLV treatment in patients with or without HCC, which is similar to several reports with a large number of cases (Sakaida et al 2017(Sakaida et al , 2020Hiramine et al 2017;Atsukawa et al 2018). The baseline dose of furosemide in responders was significantly lower than that in nonresponders (P = 0.010).…”

“…First, the present study is a small-sized single-center study in which only 20 patients were included. Blood urea nitrogen was not found as a predictive factor of treatment effect, as reported previously (Sakaida et al 2020), which may have been due to the small sample size. Second, in the present cohort study, many enrolled patients displayed relatively preserved renal function.…”

“…In this cohort, six out of seven patients with viral liver disease were TLV responders, which were considered to be influenced. In fact, in three studies with a large number of cases, there was no significant difference in the treatment effect in patients with viral and non-viral liver diseases (Hiramine et al 2017;Atsukawa et al 2018;Sakaida et al 2020). There are several limitations to the present study.…”

“…The approved indications of TLV use in Japan are fluid retention due to heart failure or liver cirrhosis, and to delay progression of autosomal dominant polycystic kidney. Previous studies have shown that a ther-apeutic response is obtained in only 60% of patients treated with TLV (Hiramine et al 2017;Atsukawa et al 2020;Sakaida et al 2020). Several factors that could predict TLV treatment efficacy have been reported.…”

“…Several factors that could predict TLV treatment efficacy have been reported. For example, increased blood urea nitrogen levels have been associated with a poor response to TLV, but the cutoff used to assess this varies between studies (Atsukawa et al 2018;Sakaida et al 2020). Patients with a higher hepatic venous pressure gradient also had a poor response to TLV (Nakagawa et al 2016), but measuring hepatic venous pressure is difficult in clinical practice.…”