Background: Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which... Show moreBackground: Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH. Method:s: CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks. Discussion: The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases. Show less
Objective Type 2 diabetes mellitus is a metabolic disorder characterized by insulin resistance. Previous studies in patients demonstrated that plasma levels of cathepsin D (CTSD), which is... Show moreObjective Type 2 diabetes mellitus is a metabolic disorder characterized by insulin resistance. Previous studies in patients demonstrated that plasma levels of cathepsin D (CTSD), which is optimally active in the acidic environment of lysosomes, correlate with insulin resistance. As plasma pH is slightly reduced in type 2 diabetic patients and we have previously shown that plasma CTSD activity is causally linked to insulin levelsin vivo, it is likely that the activity of CTSD in plasma will be increased in type 2 diabetes compared to healthy individuals. However, so far the interaction between CTSD activity and levels to postprandial metabolic derangements in type 2 diabetes is not known. Methods Eighteen type 2 diabetes and 16 age-matched healthy males were given 2 consecutive standardized mixed meals, after which blood samples were collected. Plasma metabolic parameters as well as CTSD levels and activity were measured, and changes in plasma pH was assessed. Results In line with the elevation of plasma free fatty acids (FFA) levels in male type 2 diabetics patients, plasma pH in type 2 diabetic individuals was decreased compared to male healthy individuals. While plasma CTSD levels were similar, plasma CTSD activity was increased in male type 2 diabetic compared to male healthy individuals. Besides, plasma CTSD activity rather than levels significantly correlated with indicators of type 2 diabetes (HbA1c, HOMA-IR and glucose). Furthermore, FFA was also independently associated with plasma CTSD activity (standardized beta = 0.493, p = 0.007). Conclusions Despite similar plasma CTSD levels, type 2 diabetic male individuals showed increased plasma CTSD activity compared to healthy males, which was independently linked to plasma FFA levels. Our data therefore point toward plasma CTSD as a metabolic regulator in male type 2 diabetes. Show less
NAFLD is closely related with the metabolic syndrome (MetS) and increased risk of cardiovascular disease. Liver fat associates with post-prandial hypertriglyceridemia, potentially contributing to... Show moreNAFLD is closely related with the metabolic syndrome (MetS) and increased risk of cardiovascular disease. Liver fat associates with post-prandial hypertriglyceridemia, potentially contributing to triglyceride-enrichment of high-density lipoproteins (HDL-TG), and subsequent HDL dysfunction. We assessed liver fat by MR spectroscopy, and its association with HDL physiochemical properties, and endothelial function, measured as flow-mediated dilation (FMD), before and following three consecutive meals, in 36 men with type 2 diabetes mellitus (T2DM), with the MetS, and controls. Plasma triglycerides increased significantly following the meals (P < .001). Fasting HDL-TG was highest in T2DM, relative to MetS and controls (P = .002), and increased post-prandially in all groups (P < .001). HDL function was negatively associated with HDL-TG following three meals (r = -.32,P<.05). Liver fat associated with HDL-TG after three meals (r = .65,P < .001). HDL-TG was independently associated with FMD following three consecutive meals (r = -.477,P = .003). We conclude liver fat is associated with post-prandial HDL-TG enrichment which was closely related with endothelial and HDL dysfunction. Show less
