Albunni, Hashem

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are among the most prevalent causes of chronic liver disease worldwide, closely linked to the global rise in overweight and obesity, type 2 diabetes, and metabolic syndrome. Until recently, treatment options were limited to lifestyle interventions, with no approved pharmacologic therapies. Resmetirom, a liver-directed, selective thyroid hormone receptor beta (THR-β) agonist, is a promising disease-modifying agent that targets hepatic lipid metabolism, inflammation, and fibrosis. Clinical trials, including the pivotal phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials, have demonstrated significant improvements in liver fat reduction, lipid profiles, histological endpoints, and health-related quality of life, with a favorable safety profile. In March 2024, the FDA granted accelerated approval of resmetirom for adults with MASH and moderate-to-advanced fibrosis, marking a significant milestone in MASLD treatment. This review discusses the mechanistic rationale, preclinical data, and pivotal clinical trial outcomes supporting resmetirom’s role in MASLD/MASH management, while outlining ongoing research needs, including long-term safety, pediatric evaluation, and biomarker development for optimized patient selection.

INTRODUCTION: Inadequate bowel preparation (IBP) before colonoscopy remains a common problem. This meta-analysis aimed to assess the risk factors associated with IBP. METHODS: We searched multiple databases for studies that assessed risk factors for IBP after adjustment and reported the data as adjusted odds ratios with 95% confidence intervals. Meta-analyses were conducted using a random-effects model, and pooled adjusted odds ratios for risk factors reported in ≥ 3 studies were constructed. RESULTS: One hundred fifty-four studies with 358,257 participants were included. We analyzed 48 unique risk factors. Sociodemographic predictors of IBP were Medicaid insurance, obesity, current tobacco use, age ≥ 65 years, Black race, low education level, male sex, and unmarried status. Comorbidity-related predictors of IBP were any psychiatric disease, cirrhosis, American Society of Anesthesiologists (ASA) class ≥ 3, poor functional status, constipation, diabetes, previous abdominopelvic surgery, and hematochezia. Medication-related predictors of IBP were tricyclic antidepressants, antidepressants, opioids, nontricyclic antidepressants, and calcium channel blockers. Preparation/procedure-related predictors of IBP were brown liquid rectal effluent, any incomplete bowel preparation (BP) intake, lack of split-dose BP, increased BP-to-defecation interval, any nonadherence to dietary instructions, increased BP-to-colonoscopy interval, any BP intolerance, previous IBP, and inpatient status. Although afternoon colonoscopy was a predictor of IBP, subgroup analysis of prospective studies revealed no significant association. DISCUSSION: Our meta-analysis focused on adjusted risk factors to provide precise estimates of the most important risk factors for IBP. Our findings could help develop a validated prediction model to identify high-risk patients for IBP, improve colonoscopy outcomes, reduce the need for repeat colonoscopies, and reduce associated healthcare costs.