Histological activity score on baseline liver biopsy can predict non-response to steroids in patients with severe alcoholic hepatitis

Baseline clinical and biochemical parameters fail to predict non-response to steroids in severe alcoholic hepatitis patients. Liver biopsy features have not been adequately assessed for predicting response to steroid therapy in severe alcoholic hepatitis. We aimed to identify histological parameters, which can predict steroid response in severe alcoholic hepatitis (SAH). We analyzed histological data of 107 SAH patients (71 in a derivative and 36 in a validation cohort) who presented within 4 weeks after inset of jaundice and were prospectively treated with steroids (40 mg/day). Histopathological parameters were semi-quantitatively scored in the pre-therapy biopsies in the derivative cohort, and a histological scoring system of SAH was developed which differentiated between steroid responders (Lille score < 0.45 at day 7) and non-responders. Seventeen of the 71 (24%) patients in the derivation cohort and 9 of 36 (25%) in the validation cohort were non-responders to steroids. In the derivation cohort, in comparison to responders, non-responders had higher severity of ballooning degeneration (BD) (mean 3.87 ± 0.91 versus 2.92 ± 1.33; p = 0.013) and density of Mallory-Denk bodies (MD) (mean 2.27 ± 0.79 versus. 1.69 ± 0.97; p = 0.028) on liver histology. A score derived using BD and MD (range 0-8) had high sensitivity (81%), specificity (64%), and negative predictive value (91%) in identifying patients who did not respond to steroids. The AUROC for a combined MD and BD score of > 5 for predicting steroid non-response was 0.731. Baseline histological parameters in SAH, ballooning degeneration, and Mallory-Denk bodies can reliably identify non-response to corticosteroids and help to stratify patients prior to introduction of therapy.