Association of 5-hydroxytryptamine 3 receptor antagonists with prognosis in patients with advanced hepatocellular carcinoma: A propensity score-matched study

Abstract

5-Hydroxytryptamine and its receptor are involved in hepatocarcinogenesis. This study investigated the effects of 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) on the prognosis of patients with advanced hepatocellular carcinoma (HCC). Patients with advanced HCC who received best supportive care were analyzed. Overall survival (OS) between 5-HT3RA users and nonusers was compared. Propensity score matching (PSM) was used to balance variables. Factors associated with prognosis were identified by Cox regression. A total of 1141 patients with advanced HCC were included and 102 of them received 5-HT3RAs. 5-HT3RA treatment was significantly associated with reduced mortality [hazard ratio (HR) = 0.690; 95% confidence interval (CI): 0.546–0.871; p = 0.002]. After 1:2 PSM (n = 89 and n = 161 in 5-HT3RA user and nonuser groups, respectively), 5-HT3RA treatment remained significantly associated with reduced mortality (HR = 0.615; 95% CI: 0.457–0.829; p = 0.001). Subgroup analysis of hepatitis B virus-associated HCC patients yielded similar findings. Subgroup analysis of 5-HT3RAs also yielded similar findings, showing that the 5-year OS was significantly higher in tropisetron users than nonusers (23.7% vs. 10.9%, p = 0.004) after PSM. The use of ondansetron (HR = 0.603; 95% CI: 0.365–0.995; p = 0.048) or tropisetron (HR = 0.477; 95% CI: 0.299–0.759; p = 0.002) was independent factor associated with improved prognosis after PSM. Taken together, this study shows that the use of 5-HT3RAs is associated with improved OS and the use of ondansetron or tropisetron was independently associated with a better prognosis in patients with advanced HCC, indicating a favorable effect of 5-HT3RAs on HCC patients.

The authors' abstract, as published at the source. PLoS ONE, 2026 · DOI ↗