Background Patients colonized with carbapenem resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT) with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. Methods Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray sub-distribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. Results 840 LT recipients found to be colonized with CRE before (n=203) or after (n=637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (IQR 9-42) days after LT. Pre-and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical re-intervention were retained in the prediction model. Median 30 and 60-day predicted risk was 15% (IQR 11-24%) and 21% (IQR 15-33%), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (AUC 74.6, Brier index 16.3) and bootstrapped validation dataset (AUC 73.9, Brier index 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. Conclusions Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared with best supportive care (BSC) in LT patients after sorafenib discontinuation. This observational multicenter retrospective study included LT patients with HCC recurrence who discontinued first‐line sorafenib. Group 1 comprised regorafenib‐treated patients, whereas the control group was selected among patients treated with BSC due to unavailability of second‐line options at the time of sorafenib discontinuation and who were sorafenib‐tolerant progressors (group 2). Primary endpoint was overall survival (OS) of group 1 compared with group 2. Secondary endpoints were safety and OS of sequential treatment with sorafenib + regorafenib/BSC. Among 132 LT patients who discontinued sorafenib included in the study, 81 were sorafenib tolerant: 36 received regorafenib (group 1) and 45 (group 2) received BSC. Overall, 24 (67%) patients died in group 1 and 40 (89%) in group 2: the median OS was significantly longer in group 1 than in group 2 (13.1 versus 5.5 months; P < 0.01). Regorafenib treatment was an independent predictor of reduced mortality (hazard ratio, 0.37; 95% confidence interval [CI], 0.16‐0.89; P = 0.02). Median treatment duration with regorafenib was 7.0 (95% CI, 5.5‐8.5) months; regorafenib dose was reduced in 22 (61%) patients for adverse events and discontinued for tumor progression in 93% (n = 28). The median OS calculated from sorafenib start was 28.8 months (95% CI, 17.6‐40.1) in group 1 versus 15.3 months (95% CI, 8.8‐21.7) in group 2 (P < 0.01). Regorafenib is an effective second‐line treatment after sorafenib in patients with HCC recurrence after LT.

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