BACKGROUND Ramadan fasting (RF) is a form of time-restricted feeding, where individuals abstain from eating and drinking from dawn to sunset. RF has been shown to have positive effects on weight loss, as well as vascular and metabolic disorders. We evaluated the effects of RF on the metabolic profiles of a cohort of Muslims in San Antonio. FibroScan (vibration-controlled transient elastography + controlled attenuation parameter) was used to assess liver stiffness and steatosis before and after RF. AIM To evaluate the effects of RF on metabolic and liver profiles, including body mass index (BMI), metabolic syndrome (MS), and hepatic steatosis, in a cohort of Muslims residing in San Antonio. METHODS A total of 41 subjects residing in San Antonio, TX, who fasted for 14-15 hours daily for 30 consecutive days during Ramadan, were included in this study. Subjects with any alcohol intake, chronic hepatitis (B and C), pregnancy, or use of hepatotoxic/steatotic agents were excluded. All subjects completed two visits (within 1-2 weeks before and after Ramadan). Each visit involved measurements of BMI, blood pressure, metabolic markers (fasting lipid panel and glucose), liver tests [gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin (total and indirect), albumin], and FibroScan measurements. RESULTS Prior to RF, 29% had MS and 37% had BMI ≥ 30. MS was present in 11% with BMI < 30 and 60% with BMI ≥ 30 (P = 0.01). Hepatic steatosis was more prevalent in the BMI ≥ 30 group (66% vs 30%, P = 0.02) and correlated with BMI (r = 0.54, P = 0.0003). Most participants had mild fibrosis (F0-1 or F2), with advanced fibrosis in 8% (BMI < 30) and 14% (BMI ≥ 30). Liver enzymes were largely normal at baseline. After 30 days of RF, body weight and BMI significantly decreased (P < 0.0001), while MS prevalence remained unchanged. Controlled attenuation parameter scores improved significantly overall (278.6 dB/m to 264.4 dB/m, P < 0.0001) and within both BMI groups, with no major changes in glucose, lipids, or aminotransferases. CONCLUSION In this South Asian Muslim cohort, MS prevalence was high, especially in males with BMI ≥ 30. Higher BMI correlated with steatosis; 30-day RF reduced weight and improved steatosis.
INTRODUCTION:The objective of these analyses was to evaluate interim data from the ongoing, open-label, long-term efficacy and safety ASSURE study of seladelpar, a selective peroxisome proliferator-activated receptor δ agonist, in primary biliary cholangitis. METHODS:Patients rolling over from the phase 3, randomized, placebo-controlled, 12-month RESPONSE study or with previous participation in earlier legacy seladelpar studies were enrolled. Interim evaluations included composite biochemical response (alkaline phosphatase <1.67 upper limit of normal, total bilirubin ≤ upper limit of normal, and alkaline phosphatase decrease ≥15%), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety. RESULTS:At interim cutoff, 337 patients were enrolled and received ≥1 seladelpar 10 mg dose: 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies. The composite response rate at RESPONSE completion was 62% (79/128) with seladelpar and 20% (13/65) with placebo. After 12 months in ASSURE, among patients who rolled over from RESPONSE, response rates were 72% (21/29) in patients continuing seladelpar and 94% (15/16) in crossover seladelpar patients. In legacy trial patients, response rates were 73% (120/164) and 70% (69/99) after 12 and 24 months of treatment in ASSURE, respectively. The NRS decrease at RESPONSE completion in seladelpar-treated patients with baseline NRS ≥4 (-3.4) was maintained after 6 additional months of treatment (-3.8); changes were similar in crossover seladelpar (-3.8) and legacy patients (-3.5) after 6 months of treatment in ASSURE. No seladelpar-related serious adverse events were reported. DISCUSSION:Seladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with primary biliary cholangitis with up to 2 years of treatment and remained overall safe with long-term use. Clinicaltrials.gov: NCT03301506.
