IDDF2021-ABS-0089 Primary norfloxacin prophylaxis reduces the incidence of infections in severe alcoholic hepatitis-A double-blind, randomized controlled study

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<h3>Background</h3> Steroid therapy is the standard of care for severe alcoholic hepatitis (sAH) at most centres. However, steroids are associated with an increased risk of infections. Therefore, we aimed to compare the outcomes of patients receiving concomitant norfloxacin (NFX) with steroids in patients with sAH. <h3>Methods</h3> In this double-blind, randomized study, acute-on-chronic liver failure (ACLF) patients without sepsis, hepatic encephalopathy, or SBP were assigned to receive oral NFX 400mg or matched placebo (PBO) once daily for 30 days along with standard medical therapy. 143 ACLF patients were included (CTRI/2019/10/021548). On subgroup analysis, 20 in the NFX group and 13 patients in the PBO group received concomitant steroid therapy for sAH. The primary objective was to assess the incidence of infections at days 30, 90, and the secondary was to evaluate the transplant-free survival (TFS) at days 30, 90. <h3>Results</h3> Baseline characteristics were similar in both the groups (MELD-NFX-27.8±3.79 vs. PBO-29.62±4.66; P=0.229). The incidence of infection was lower with NFX (10%) than PBO (38.5%) at day 30 (P=0.066). The incidence of infection at day 90 was lower with NFX (30%) than PBO (69.2%) (P=0.027) (IDDF2021-ABS-0089 Figure 1. Kaplan Meier analysis of infection incidence at days 30, 60 and 90). TFS was similar in both groups at day 30 (NFX-85% vs. PBO-77%; Log-Rank test: P=0.524). However, TFS at day 90 was better with NFX (85%) than placebo (53.8%) (Log-Rank test: P=0.059). The most common source of infection was the urinary tract (NFX - 3 vs. Placebo-4). E. coli was the commonly isolated organism in both groups. Candida albicans were isolated in two patients in NFX group, while none in the PBO group developed fungal infection. Sepsis was the common cause of mortality (NFX-2; PBO-4). Further, one patient in NFX group succumbed to post-TIPS liver failure (for variceal bleed). There were no drug-related adverse events in this sub-group of patients. <h3>Conclusions</h3> Primary norfloxacin prophylaxis is safe and effective in reducing infections in patients with sAH receiving steroid therapy.