Early prognostic biomarkers of corticosteroid response in severe alcohol-related hepatitis: insights from a retrospective study
Background and aims: Severe alcohol-related hepatitis (sAH) is associated with high mortality. The response to corticosteroids remains unpredictable and can only be assessed after seven days of treatment using the Lille model. Early identification of non-responders (PNR) could optimize management and avoid unnecessary risks. We aimed to identify baseline fecal and circulating biomarkers predicting corticosteroid non-response. Approach &amp; Results: We retrospectively included 63 biopsy-proven sAH patients treated with prednisolone. We characterized their baseline gut microbiota (GM) using shotgun metagenomics in combination with short-chain fatty acids and bile acids (BA) profiling. PNR and prednisolone responders (PR) had a comparable baseline degree of liver injury (median Maddrey discriminant function: 50.0 for PR vs. 55.5 for PNR, p = 0.307, Wilcoxon). However, circulating eosinophil counts were significantly lower in PNR compared to PR (1.0 x 108/L vs. 2.0 x 108/L, p = 0.013, Wilcoxon), with a similar trend for basophil counts (0.0 x 108/L vs. 0.0 x 108/L, p = 0.063, Wilcoxon). Baseline GM diversity was comparable for both groups (Shannon index: 2.2 for PR vs. 2.5 for PNR, p = 0.765, Student), while quantitative polymerase chain reaction revealed that Prevotella spp. were depleted in the GM of PNR (5.5 vs. 5.2 log10 copies/ng of DNA, p = 0.054, Wilcoxon). PNR had significantly lower fecal and serum levels of several BA, suggesting an altered enterohepatic circulation before treatment compared to PR, despite comparable degree of hepatopathy. Conclusions: Baseline BA and immune granulocyte profiles provide promising non-invasive biomarkers for clinical decision-making in sAH management.