Rifaximin Use Is Associated With Prognosis and Recurrence Patterns in Spontaneous Bacterial Peritonitis: Exploratory Insights Into the Oral–Gut–Hepatic Axis

ABSTRACT Background Spontaneous bacterial peritonitis (SBP) remains a life‐threatening complication in cirrhotic patients with refractory ascites. Evidence for rifaximin (RFX) in SBP prevention and prognosis is lacking in Japan. We investigated the effect of RFX on prognosis and recurrence of SBP and evaluated the prognostic role of oral health within the oral–gut–hepatic axis. Methods This single‐center, retrospective study included 142 patients with a first SBP episode. Patients were stratified into an RFX‐treated group and a non‐RFX group. Outcomes included 90‐day survival, SBP recurrence, and cirrhosis‐related complications. Oral health status and acid‐suppressive therapy were also evaluated. Results Forty‐seven patients received RFX. Ascitic culture positivity was comparable between groups, but RFX‐treated patients had fewer enteric bacteria and more oral flora ( p = 0.0033). Ninety‐day survival was significantly higher with RFX (85.1% vs. 60.0%, p = 0.0023). The 12‐month recurrence rate was markedly lower in the RFX‐treated group (10.4% vs. 63.2%; HR 0.19, 95% CI 0.09–0.40). Oral contamination independently predicted overt hepatic encephalopathy (HR 2.56) and variceal rupture (HR 6.72). Denture use was an independent predictor of mortality (HR 2.04, 95% CI 1.23–3.38). Conclusion Rifaximin use was associated with higher short‐term survival and lower SBP recurrence in cirrhotic patients with refractory ascites. Oral contamination and denture use were associated with adverse outcomes, providing novel clinical evidence for the oral–gut–hepatic axis. Integration of RFX therapy with oral hygiene interventions may offer a comprehensive strategy to improve prognosis in cirrhosis.