INTRODUCTION:This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria.METHODS:Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome.RESULTS:A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10–28.9) and 33.8% (95% CI, 23–46) (P = 0.03); and the incidence of bacterial infections at day 90 was 46% (95% CI, 34–58) and 62% (95% CI, 49.67–73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43–86.73) and 64.8% (95% CI, 52.54–75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11–69.84) and 43.7% (95% CI, 31.91–55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%).DISCUSSION:Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.

Aim Nonselective beta‐blockers (NSBBs) can reduce the incidence of complications in patients with cirrhosis and prolong survival. The safety and efficacy of NSBBs in real‐world settings in patients with acute‐on‐chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of Liver criteria are unknown. This study aimed to assess the safety and efficacy of NSBBs in patients with Asian Pacific Association for the Study of Liver (APASL)‐defined ACLF Methods In this retrospective, multicenter study, patients with ACLF with complete 30 days follow‐up from January 2019 to December 2021 were included. The primary objective was to compare 30‐day mortality among standard of care (SOC) and NSBB (+SOC) groups. The secondary objectives were to compare the incidence of infection, variceal bleed, and recompensation among both the groups. Results A total of 346 patients were included. Only 26% (n = 89) of them received NSBBs, while 74% (n = 257) received only SOC. On Kaplan–Meier analysis, the incidence of mortality was 21% (95% confidence interval [CI]: 16.20–26.50) in SOC group compared to only 8% (95% CI: 3.22–15.53) in NSBB group at Day 30 (p = 0.005). Similarly, mortality in SOC group was 63% (95% CI: 56.81–69.00) compared to 46% (95% CI: 35.44–57.00) in NSBB group at 1 year (p = 0.001). NSBB therapy could not reduce the incidence of infections or variceal bleed. Forty‐seven percent of patients in the SOC group and 73% of patients in the NSBB group (p < 0.001) recompensated. Carvedilol was prescribed in 77.5% and propranolol in 22.5% of patients. Conclusions NSBBs reduce mortality without any effect on infection or variceal bleed in patients with ACLF. However, only one in four ACLF patients are suitable for NSBB therapy.