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

ABSTRACT 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.