Prevalence of Hepatic Steatosis After Islet Transplantation and Its Relation to Graft Function

Abstract

Islet allotransplantation can provide insulin independence in selected individuals with type 1 diabetes. The long-term effects of these transplants on the liver are unknown. Recently, two cases of periportal steatosis after islet transplantation have been described. In this study, we performed ultrasound and magnetic resonance imaging (MRI) in 30 C-peptide؊positive islet transplant recipients to detect steatosis and to explore the association of the radiological findings with clinical and metabolic factors. Steatosis was observed on MRI in six (20%) subjects. Histological findings of hepatic steatosis concurred with the imaging findings. Steatosis completely resolved in one subject whose graft failed. More subjects with steatosis required supplementary exogenous insulin than not (67 vs. 21%; P < 0.05). The clinical features of subjects with and without steatosis were otherwise similar, although C-peptide levels were higher in insulin-independent subjects with steatosis S uccessful islet transplantation using a steroidfree, sirolimus-based immunosuppressive regimen (the Edmonton protocol) has emerged as an effective treatment for type 1 diabetic subjects at major risk from hypoglycemia and metabolic lability (1). Although islet autotransplants have functioned for Ͼ18 years without clinical consequence, the long-term effects of persistent allotransplanted islets on the liver after portal venous delivery have not been well defined in large patient cohorts.Clearly a number of factors might result in structural/ functional changes in the liver: 1) the procedure itself, including ablative approaches used to prevent bleeding from the catheter tract; 2) the physical embolization of terminal branches of the portal vein by islets and the local effects of peri-islet micro-thrombi; 3) the local effects on the hepatocyte of high concentrations of insulin released from the transplanted islets; 4) the effects of immunosuppressive drugs on the liver; and 5) structural changes, including local scarring after rejection and clearance of islet tissue within the liver. Ultrasound and magnetic resonance imaging (MRI) are noninvasive techniques that facilitate definition of hepatic structure and can be repeated safely to follow changes over time.An examination of radiological changes after islet transplantation is important for the clinical care of transplant patients and to learn more about the function of transplanted islets over time. Knowledge of normal abdominal appearance after islet transplantation is helpful for future interpretation when these patients present with abdominal pathology unrelated to their islet transplant.Recently, two cases of periportal steatosis after intraportal islet allotransplantation, apparent on MRI examination, have been described in a small series of four subjects (2). The appearance of steatosis was attributed to intrahepatic insulin secretion and was proposed as a marker of functional islet graft survival. Preliminary data from Maafi et al. (3) also have demonstrated both ultrasonographic and histo...

Optimising islet engraftment is critical for successful clinical islet transplantation

“…The initial stages in the process leading to these pathological conditions were hepatocyte steatosis and glycogen deposits in the vicinity of the transplanted islets, findings that are analogous to those reported in patients from several transplant centres [37,38]. In addition, islets in the liver are exposed to toxic products from the gastrointestinal tract, including high concentrations of the immunosuppressive drugs being administered [7,8].…”

Intrahepatic Transplanted Islets in Humans Secrete Insulin in a Coordinate Pulsatile Manner Directly Into the Liver

“…Hepatic steatosis occurs in a subgroup of patients after successful intraportal islet transplantation (31,32). Graft failure was associated with reversal of this lesion (32). Such findings could indicate that insulin released by intraportal islet grafts into the liver sinusoids induces lipid deposition, e.g., via promoting the esterification of free fatty acids within the hepatocytes.…”

“…Hepatic steatosis occurs in a subgroup of patients after successful intraportal islet transplantation (31,32). Graft failure was associated with reversal of this lesion (32).…”

Single-centre experience of extending indications for percutaneous intraportal islet autotransplantation (PIPIAT) after pancreatic surgery to prevent diabetes: feasibility, radiological aspects, complications and clinical outcome

“…Graft loss was registered in a low percentage of patients [3/34 (9%) patients] with C-peptide levels ,0.3 ng ml 21 ; 1 among these patients showed hepatic steatosis 6 months after PIPIAT, disappearing 6 months later. The role of imaging in islet transplantation 36,37 and particularly in the presence of hepatic steatosis at ultrasound or MRI after pancreatic islet transplantation has been a concern of debate: [38][39][40] some authors relate this phenomenon to the lipogenic action of pancreatic cells without any specific correlation to graft function; 38,39 conversely, the authors of the present study consider hepatic steatosis as an early marker of graft disfunction. 18 This hypothesis is also supported by the evidence that patients with autotransplantation, which is demonstrated to achieve a better clinical outcome, register a lower percentage of hepatic steatosis than patients with allotransplantation.…”