Impact of Helicobacter pylori on Immune Checkpoint Inhibition in Hepatocellular Carcinoma: A Multicenter Study

Introduction: Immunomodulating effects of Helicobacter pylori (H. pylori) have been shown to inhibit antitumor immunity. Resistance to immune checkpoint inhibitor (ICI)- based therapies is common among patients with hepatocellular carcinoma (HCC). This study aimed to assess the effect of H. pylori on the outcomes of ICI in patients with HCC. Methods: We conducted a multicenter study in patients with HCC across a broad range of treatments. Patients received either ICI-based combination regimens or sorafenib-based therapy. H. pylori serostatus and virulence factors were determined and correlated with overall survival (OS), progression-free survival (PFS), and safety across the treatment modalities. Results: 180 patients with HCC were included; among these, 64 were treated with ICI-based regimen and 116 with sorafenib-based regimen. In patients treated with ICI, median OS was shorter in H. pylori- positive patients (10.9 months in H. pylori-positive vs. 18.3 months; p = 0.0384). H. pylori positivity was associated with a shorter PFS in ICI recipients (3.9 months vs. 6.8 months, p = 0.0499). In patients treated with sorafenib, median OS was not shorter among H. pylori-positive patients (13.4 months in H. pylori-positive vs. 10.6 months; p = 0.3353). Immunerelated adverse events and rates of gastrointestinal bleeding were comparable between H. pylori-positive and -negative patients. Conclusion: H. pylori seropositivity was linked to poorer outcomes in patients with HCC treated with ICI. This association was not observed among patients receiving sorafenib-based therapies.