Impact of Intestinal Colonization with Clostridioides difficile on Clinical Outcomes in Alcohol-associated Hepatitis

INTRODUCTION: Clostridioides difficile (C. difficile) is associated with reduced intestinal microbial diversity, and evidence links dysbiosis to increased disease severity in alcohol-associated hepatitis (AH). We therefore evaluated CDC as a predictor of clinical outcomes in AH. METHODS: We conducted a retrospective cohort study of 471 patients hospitalized with AH who underwent C. difficile surveillance from July 2017 to September 2024. CDC was defined as positive toxigenic C. difficile rectal swab PCR without symptoms. Patients were followed for 90 days after admission. RESULTS: 69 AH patients (14.7%) had CDC. 163 (34.6%) developed infections, and infection rates were higher in CDC patients [53.6% vs. 31.3%, p=0.001], including C. difficile infection (CDI, 8.7% vs. 0.8%, p<0.01). Patients with CDC had more ascites (78.3% vs. 22.5%, p<0.001), gastrointestinal (GI) bleeding (39.1% vs. 27.9%, p=0.042), and ICU admission (46.4% vs. 34.6%, p=0.042), but MELD 3.0 was similar between groups [28 (IQR 23 - 35) vs. 26 (IQR 21 - 31), p=0.065]. 90-day survival was lower with CDC [66.7 (95% CI 58.9 - 74.4) days vs. 77.2 (95% CI 74.6 - 79.9) days, p=0.007]. Age [aHR 1.039 (95% CI 1.021 - 1.057), p<0.001], MELD 3.0 [aHR 1.103 (95% CI 1.083 - 1.124), p<0.001] and CDC [aHR 1.604 (95% CI 1.014 - 2.537), p=0.043] were associated with 90-day mortality. CONCLUSION: In AH, CDC is associated with more infection, ascites, gastrointestinal bleeding, and ICU admission, and independently predicts reduced 90-day survival. CDC may serve as a novel marker of disease severity and infection risk in AH.