Background & Aims: Definitions of primary biliary cholangitis (PBC) treatment response commonly include alkaline phosphatase (ALP) <1.67× upper limit of normal (ULN). However, ALP >ULN is associated with active disease and reduced transplant-free survival, whereas ALP normalization is associated with better complication-free survival. Elafibranor, a peroxisome proliferator-activated receptor (PPAR)-α/δ agonist, has been shown to be effective and well-tolerated as a second-line treatment in patients with PBC and ALP ≥1.67x ULN. We report phase III ELSPIRE trial results, evaluating the effect of one year of elafibranor treatment on ALP normalization (ALP ≤ULN; ≤120 U/L) in patients with PBC and ALP >1–<1.67× ULN after incomplete response/intolerance to ursodeoxycholic acid. Approach & Results: In ELSPIRE, 92 patients were randomized, double-blind, 2:1 to elafibranor 80 mg (n=62) or placebo (n=30) for 52 weeks, stratified by ALP at randomization (>1–≤1.33× ULN vs. >1.33–<1.67× ULN). At Week 52, 85.3% of patients receiving elafibranor achieved the primary endpoint of ALP normalization, versus 23.3% receiving placebo (treatment difference: 62.0%; 95% CI: 44.3, 79.7; p <0.0001). Least squares mean percentage change from baseline in ALP at Week 52 was –36.5% with elafibranor versus –4.2% with placebo ( p <0.0001). A greater proportion of patients receiving elafibranor versus placebo achieved ALP normalization with ≥15% reduction from baseline and complete biochemical response (normal ALP, total bilirubin, transaminases, albumin, and INR). Elafibranor was well tolerated; no new safety signals were observed. Conclusions: These results support elafibranor as second-line treatment with UDCA for patients with PBC and ALP >1–<1.67× ULN, with ALP normalization as an achievable treatment goal.
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.
