Browsing by Subject "MASH"

Now showing 1 - 3 of 3
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    Advancing the Metabolic Dysfunction-Associated Steatotic Liver Disease Proteome: A Post-Translational Outlook
    (MDPI, 2025-03-12) Chowdhury, Kushan; Das, Debajyoti; Huang, Menghao; Biochemistry and Molecular Biology, School of Medicine
    Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder with limited treatment options. This review explores the role of post-translational modifications (PTMs) in MASLD pathogenesis, highlighting their potential as therapeutic targets. We discuss the impact of PTMs, including their phosphorylation, ubiquitylation, acetylation, and glycosylation, on key proteins involved in MASLD, drawing on studies that use both human subjects and animal models. These modifications influence various cellular processes, such as lipid metabolism, inflammation, and fibrosis, contributing to disease progression. Understanding the intricate PTM network in MASLD offers the potential for developing novel therapeutic strategies that target specific PTMs to modulate protein function and alleviate disease pathology. Further research is needed to fully elucidate the complexity of PTMs in MASLD and translate these findings into effective clinical applications.
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    Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials
    (MDPI, 2024-10-14) Ayesh, Hazem; Beran, Azizullah; Suhail, Sajida; Ayesh, Suhail; Niswender, Kevin; Medicine, School of Medicine
    Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis evaluates their comparative efficacy and safety. Methods: A literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Included clinical trials addressed MASLD or MASH with Resmetirom, FGF21 analogs, or GLP-1 agonists. Statistical analyses used a random-effects model, calculating mean differences (MD) and relative risks (RR), with heterogeneity assessed using τ2, I2, and Q statistics. Results: MASH resolution was significantly higher for FGF21 (RR 4.84, 95% CI: 2.59 to 9.03), Resmetirom showed the most significant reduction in MRI-PDFF (MD -18.41, 95% CI: -23.60 to -13.22) and >30% fat reduction (RR 3.56, 95% CI: 2.41 to 5.26). Resmetirom significantly reduced ALT (MD -15.71, 95% CI: -23.30 to -8.13), AST (MD -12.28, 95% CI: -21.07 to -3.49), and GGT (MD -19.56, 95% CI: -34.68 to -4.44). FGF21 and GLP-1 also reduced these markers. Adverse events were significantly higher with Resmetirom (RR 1.47, 95% CI: 1.24 to 1.74), while GLP-1 and FGF21 showed non-significant trends towards increased risk. Conclusions: Resmetirom and FGF21 show promise in treating MASLD and MASH, with Resmetirom particularly effective in reducing liver fat and improving liver enzymes. GLP-1 agonists also show benefits but to a lesser extent. Further long-term studies are needed to validate these findings and assess cost-effectiveness.
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    Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting
    (Wolters Kluwer, 2025-04-03) Ravela, Neel; Shackelford, Phoebe; Blessing, Nadia; Yoder, Lindsay; Chalasani, Naga; Samala, Niharika; Medicine, School of Medicine
    Background: Resmetirom was conditionally approved in the United States recently for treating metabolic dysfunction-associated steatohepatitis with stage 2 and 3 fibrosis. However, its availability to patients requires preauthorization by the payors and is dispensed only through selected specialty pharmacies. Methods: We established a multistakeholder and multistep resmetirom prescription process pivoting to a dedicated pharmacist. It incorporates liver biochemistry testing at 12 weeks and liver clinic follow-up at 6 months after starting resmetirom. Results: Fifteen hepatology providers prescribed resmetirom to 113 patients from April 1, 2024, to November 8, 2024, with histologic eligibility in 70% and noninvasive criteria in 30%. Resmetirom treatment was approved for 110 patients (97%), including 8 patients receiving the pharmaceutical company's patient assistance and 6 patients receiving bridge support to cover the co-pay. Eighty-three patients initiated resmetirom at an average of 30 days after its prescription. Adverse events were reported by 41% of patients taking resmetirom, and they were predominantly related to gastrointestinal symptoms and pruritus and/or rash with no evidence of hypersensitivity. Thirteen patients (16%) discontinued resmetirom after an average of 25.5 days (range: 2-68 d), with 11 patients discontinuing due to adverse events. The adverse events leading to discontinuation were nausea, diarrhea, and vomiting (n=4), right upper quadrant discomfort (n=2), left lower quadrant pain (n=1), rash with pruritus (n=1), pruritus and rash with indirect hyperbilirubinemia (n=1), dizziness (n=1), and mental fogginess (n=1). Follow-up liver biochemistries available in 24 patients showed no evidence of DILI. Conclusions: Our prescription pathway effectively dispensed resmetirom to nearly all patients who were prescribed resmetirom. One in 6 patients discontinued resmetirom, primarily due to side effects. This high discontinuation rate may be mitigated by modifying our follow-up from "prescribe and forget" to "prescribe and closely follow."