The association between proton-pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy

Background and Aim

The association between long-term proton-pump inhibitors (PPIs) use and malignancies had long been discussed, but it still lacks consensus. Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery.

Methods

We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non-users: < 28 cumulative defined daily dose [cDDD]; short-term users: 28–89 cDDD; mid-term users: 90–179 cDDD, and long-term users: ≥ 180 cDDD, respectively). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan–Meier method and Cox proportional hazard models.

Results

Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10 years, interquartile range [IQR] 1.49–5.01) compared with non-users (2.73 years, IQR 1.20–4.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44–0.74, P < 0.001). When considering the cumulative dosage of PPI, only long-term PPI users had significant lower risk of HCC recurrence than non-PPI group (adj-HR: 0.50; 95% CI: 0.35–0.70; P < 0.001). Moreover, the impact of long-term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non-cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non-users (4.23 years, IQR 2.73–5.86 vs 4.04 years, IQR 2.51–5.82, P = 0.369).

Conclusion

Long-term PPI use (≥ 180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy.