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

J Gastroenterol. 2020 Aug;55(8):800-810. doi: 10.1007/s00535-020-01691-x. Epub 2020 May 9.

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 ≥ 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.

Keywords: Ascites; Cirrhosis; Edema; Fibrosis; Tolvaptan.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antidiuretic Hormone Receptor Antagonists / adverse effects
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use
  • Blood Urea Nitrogen
  • Edema / drug therapy*
  • Edema / etiology
  • Female
  • Humans
  • Japan
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Liver Diseases / drug therapy*
  • Liver Diseases / etiology
  • Male
  • Middle Aged
  • Product Surveillance, Postmarketing
  • Prospective Studies
  • Tolvaptan / adverse effects
  • Tolvaptan / therapeutic use*
  • Treatment Outcome

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Tolvaptan