Prognostic Value of an Early Response to Tolvaptan and Its Clinical Implications in Patients With Cirrhosis and Hepatic Edema: A Nationwide Multicenter Cohort Study

Aim: Hepatic edema indicates a poor prognosis and impaired quality of life in patients with cirrhosis. Tolvaptan is used in Japan to treat patients who do not respond to conventional diuretics. However, the long-term prognostic effect of tolvaptan has not yet been fully determined in large-scale, real-world cohorts. Methods: We conducted a retrospective multicenter study of patients with cirrhosis and hepatic edema who were treated with tolvaptan at 17 centers to identify the clinical predictors of treatment response and long-term survival. An early response was defined as a ≥ 1.5-kg weight reduction within 7 days. Results: Of 1165 patients, 58.8% showed an early response. In a multivariate analysis, blood urea nitrogen concentrations (BUN; per 1.0-mg/dL decrease), serum sodium concentrations (per 10-mEq/L increase), and the absence of hepatocellular carcinoma were independently associated with an early response. Early responders had longer overall survival than non-responders (median, 15.3 vs. 7.7 months; p = 2.70 × 10⁻⁶). An early response remained an independent factor associated with 5-year survival (hazard ratio: 0.83; p = 2.60 × 10⁻²) after adjustment for age, hepatic functional reserve, hepatocellular carcinoma, serum sodium concentrations, and BUN concentrations. Subgroup analyses of liver-related mortality were consistent with the primary survival analysis. Conclusions: An early response to tolvaptan, which is more likely to occur in patients without elevated BUN concentrations or hyponatremia, is independently associated with improved long-term survival in patients with cirrhosis and hepatic edema. Our findings indicate the importance of initiating tolvaptan treatment before renal impairment or hyponatremia develops.