BACKGROUND: Patients with chronic intestinal failure (CIF) often develop cholestatic liver injury, which may lead to liver failure and need for organ transplantation. OBJECTIVES: The aim of this study was to investigate whether citrulline (CIT) and the enterokine fibroblast growth factor 19 (FGF19) are associated with chronic cholestasis and survival in adult CIF patients, and to develop a risk score to predict their survival. METHODS: We studied 135 adult CIF patients on intravenous supplementation (>3 mo). Associations of plasma CIT and FGF19 with chronic cholestasis and survival were estimated by logistic and Cox regression models. A predictive risk score was developed and validated internally. RESULTS: Patients with chronic cholestasis (17%) had a reduced 5-y survival rate compared with patients without chronic cholestasis (38% and 62%, respectively). In multivariable analysis, low FGF19, low CIT, and female sex were associated with chronic cholestasis. Patients with low rather than high CIT or FGF19 also had reduced 5-y survival rates (29% compared with 69%; 54% compared with 66%, respectively). Risk factors identified in multivariable analysis of survival were low FGF19 (HR: 3.4), low CIT (HR: 3.3), and number of intravenous infusions per week (HR: 1.4). These 3 predictors were incorporated in a risk model of survival termed Model for End-Stage Intestinal Failure (MESIF) (C-statistic 0.78). The 5-y survival rates for patients with MESIF scores of 0 to <20 (n = 47), 20-40 (n = 75), and >40 (n = 13) were 80%, 58%, and 14%, respectively. CONCLUSIONS: CIT and FGF19 predict chronic cholestasis and survival in this cohort of adult CIF patients, and the derived MESIF score is associated with their survival. Pending external validation, the MESIF score may help to identify patients for closer clinical monitoring or earlier referral to intestinal transplantation centers.

Department of Clinical Epidemiology and Medical Technology Assessment Maastricht University Medical Center Maastricht Netherlands

Department of Endocrinology and Metabolism Amsterdam University Medical Centers location AMC Amsterdam Netherlands

Department of Gastroenterology and Hepatology Radboud University Medical Center Nijmegen Netherlands

Department of General Visceral and Transplantation Surgery RWTH University Hospital Aachen Aachen Germany

Department of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Surgery Maastricht Netherlands

NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Maastricht Netherlands

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Chyme Reinfusion Restores the Regulatory Bile Salt-FGF19 Axis in Patients With Intestinal Failure