Please cite this article in press as: Venturini M, et al. Hepatic steatosis after islet transplantation: Can ultrasound predict the clinical outcome? A longitudinal study in 108 patients. Pharmacol Res (2015), http://dx.doi.org/10.1016/j.phrs.2015.03.002 ARTICLE IN PRESS G Model YPHRS-2789; No. of Pages 8 Pharmacological Research xxx (2015) xxx–xxx Contents lists available at ScienceDirect Pharmacological Research j ourna l h om epage: w ww.elsevier.com/locate/yphrs Hepatic steatosis after islet transplantation: Can ultrasound predict the clinical outcome? A longitudinal study in 108 patients Massimo Venturini a,∗ , Paola Maffi b , Giulia Querques c , Giulia Agostini a , Lorenzo Piemonti b , Sandro Sironi c , Francesco De Cobelli a,d , Paolo Fiorina e , Antonio Secchi b,d , Alessandro Del Maschio a,d a Department of Radiology, Scientific Institute H S. Raffaele, Milan, Italy b Department of Internal Medicine, Transplant Unit, Scientific Institute H S. Raffaele, Milan, Italy c Department of Radiology, Milano-Bicocca University, Monza, Italy d Vita-Salute S. Raffaele University, Milan, Italy e Transplantation Research Center, Harvard Medical School, Boston, MA, USA a r t i c l e i n f o Article history: Received 3 February 2015 Received in revised form 4 March 2015 Accepted 4 March 2015 Available online xxx Keywords: Type 1 diabetes Islet transplantation Ultrasound Hepatic steatosis Pancreatogenic diabetes -Score a b s t r a c t Percutaneous intra-portal islet transplantation (PIPIT) is a less invasive, safer, and repeatable therapeutic option for brittle type 1 diabetes, compared to surgical pancreas transplantation. Hepatic steatosis is a consequence of the islet engraftment but it is curiously present in a limited number of patients and its meaning is controversial. The aims of this study were to assess hepatic steatosis at ultrasound (US) after PIPIT investigating its relationship with graft function and its role in predicting the clinical outcome. From 1996 to 2012, 108 patients underwent PIPIT: 83 type-1 diabetic patients underwent allo- transplantation, 25 auto-transplantation. US was performed at baseline, 6, 12, and 24 months, recording steatosis prevalence, first detection, duration, and distribution. Contemporaneously, steatotic and non- steatotic patients were compared for the following parameters: infused islet mass, insulin independence rate, -score, C-peptide, glycated hemoglobin, exogenous insulin requirement, and fasting plasma glu- cose. Steatosis at US was detected in 21/108 patients, 20/83 allo-transplanted and 1/25 auto-transplanted, mostly at 6 and 12 months. Infused islet mass was significantly higher in steatotic than non-steatotic patients (IE/kg: S = 10.822; NS = 6138; p = 0.001). Metabolically, steatotic patients had worse basal condi- tions, but better islet function when steatosis was first detected, after which progressive islet exhaustion, along with steatosis disappearance, was observed. Conversely, in non-steatotic patients these parame- ters remained stable in time. Number of re-transplantations was significantly higher in steatotic than in non-steatotic patients (1.8 vs 1.1; p = 0.001). Steatosis at US seems to be related to the islet mass and local overworking activity. It precedes metabolic alterations and can predict graft dysfunction addressing to therapeutic decisions before islet exhaustion. If steatosis does not appear, no conclusion can be drawn. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Percutaneous intra-portal islet transplantation (PIPIT) from cadaveric donors represents a less invasive, safer, and repeatable therapeutic option for type 1 diabetes, compared to surgi- cal pancreas transplantation [1]. Combined kidney–pancreas ∗ Corresponding author at: Department of Radiology, Scientific Institute H S. Raf- faele, Via Olgettina 60, 20132 Milan, Italy. Tel.: +39 02 26436104; fax: +39 02 26432165. E-mail address: venturini.massimo@hsr.it (M. Venturini). transplantation is the best solution for patients affected by brit- tle, long-term type 1 diabetes and chronic renal insufficiency [2]. Since the 1990s, islet after kidney transplantation (IAK) has rep- resented a valid solution to simultaneously cure diabetes [3] and chronic renal failure [4] in case of pancreas unavailability from a deceased donor at the time of the kidney transplant. Islet transplan- tation alone (ITA) is performed in brittle, short-term type 1 diabetic patients with good renal function to achieve insulin independence or, at least, reduce exogenous insulin requirement, prevent hypo- glycemic episodes [5] and diabetic complications [6], improving patients’ quality of life [7]. Since 2000, ITA is performed according to the Edmonton protocol based on the infusion of an adequate islet http://dx.doi.org/10.1016/j.phrs.2015.03.002 1043-6618/© 2015 Elsevier Ltd. All rights reserved.