Proton pump inhibitor therapy is associated with reduced survival following first-time transarterial chemoembolization in patients with hepatocellular carcinoma

Abstract

Background and aims: Several studies have reported associations of proton pump inhibitor (PPI) treatment with the incidence of complications and even increased mortality in patients with liver cirrhosis. Up to now, there are no studies on the impact of PPI treatment in patients with hepatocellular carcinoma (HCC). Therefore, the aim of our study was to investigate the prognostic effects of PPI treatment in a cohort of patients with HCC treated by transarterial chemoembolization (TACE).

Methods: Three hundred fifty-eight patients with HCC that received first-time TACE were included in a retrospective analysis. We explored effects of PPI treatment using uni- and multivariable regression models.

Results: One hundred sixty-seven of the 358 patients (46.6%) received PPI treatment. Median transplant-free survival after TACE was significantly lower in patients treated with PPIs compared to patients without PPI treatment [16.0 (10.7-21.3) months vs. 26 (22.2-29.8) months, P = 0.006]. Importantly, PPI treatment remained a significant prognostic factor for reduced survival after adjustment for patient demographics, tumor stadium and liver function [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.09-1.78, P = 0.005]. We observed a dose-dependent association of PPI treatment with survival: A higher daily PPI dose was an independent prognostic factor for reduced survival (HR 1.32, 95% CI 1.14-1.54, P < 0.001). Notably, 58.1% of patients receiving PPIs had no clear indication therefor.

Conclusion: PPI treatment is associated with reduced survival in patients with HCC in a dose-dependent manner. Thus, indication for PPI treatment should be evaluated attentively in these patients. Further, prospective studies are needed to validate the findings of this study.