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All Journal Eureka Herba Indonesia Sriwijaya Journal of Radiology and Imaging Research
Arsan Saliha
Department of Internal Medicine, Phlox Institute, Palembang, Indonesia
Dentistry Health Professions Medicine & Pharmacology Neuroscience Physics

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Longitudinal MRI-PDFF Quantification of Hepatic Steatosis Reversibility During SGLT2-Inhibitor versus GLP-1 Receptor Agonist Therapy: A Prospective Cohort Study Arsan Saliha; Dedi Sucipto; Mischa Chantal Adella; Ericca Dominique Perez
Sriwijaya Journal of Radiology and Imaging Research Vol. 3 No. 2 (2025): Sriwijaya Journal of Radiology and Imaging Research
Publisher : Phlox Institute: Indonesian Medical Research Organization

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59345/sjrir.v3i2.292

Abstract

Introduction: Precise quantification of hepatic steatosis is central to managing metabolic dysfunction-associated steatotic liver disease (MASLD). MRI proton density fat fraction (MRI-PDFF) has displaced biopsy as a reproducible biomarker, yet real-world comparative monitoring data and formal early-response prediction remain scarce in Indonesian practice. We quantified steatosis reversibility on serial MRI-PDFF during SGLT2-inhibitor versus GLP-1 receptor agonist therapy and tested whether an early scan predicts response. Methods: In this prospective cohort at a tertiary hospital in Palembang, Indonesia, 90 adults with MASLD (baseline PDFF ≥5.5%) were grouped by prescribed therapy (SGLT2i, n=45; GLP-1 RA, n=45) and imaged at baseline, Month 3 and Month 6 on a 3.0 T scanner using a confounder-corrected 3D multi-echo spoiled gradient-echo sequence. Two blinded radiologists measured PDFF across Couinaud segments V/VI/VIII; response was a ≥30% relative reduction. Analyses (STARD 2015) included linear mixed-effects modelling, κ and intraclass correlation, ROC (DeLong), likelihood ratios and multivariable logistic regression. Results: PDFF fell in both arms (both p<0.001; partial η²=0.66 and 0.79). Responder rate was 75.6% (95% CI 61.3–85.8) with GLP-1 RA versus 40.0% (27.0–54.5) with SGLT2i (OR 4.64; p=0.001). A Month-3 decline ≥16.9% predicted Month-6 response with AUC 0.895 (0.823–0.967), sensitivity 96.2%, specificity 78.9%, LR+ 4.57, LR− 0.05. Inter-reader agreement was near-perfect (ICC 0.986; κ 0.861). GLP-1 RA therapy and higher baseline PDFF independently predicted response. Conclusion: Serial MRI-PDFF reliably quantified pharmacologically-induced steatosis reversibility, with GLP-1 RA producing greater fat loss and an early scan accurately triaging responders. MRI-PDFF is a robust, decision-useful monitoring biomarker deployable in tertiary settings.
Multi-Target Modulation of the Gut-Liver Axis by Beras Kencur and Kunyit Asam Phytomolecules: Shotgun Metagenomic Re-Analysis, AGORA2 Metabolic Flux Modeling, and Biosynthetic Enzyme Docking in Metabolic Steatohepatitis Louisa Istarini; Arsan Saliha
Eureka Herba Indonesia Vol. 6 No. 2 (2025): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v6i2.151

Abstract

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is driven by breakdown of the gut-liver axis. Loss of short-chain fatty acid (SCFA)-producing commensals weakens mucosal tight junctions and allows portal translocation of lipopolysaccharide (LPS), which activates hepatic Kupffer cells and promotes fibrosis. The Indonesian Jamu formulations Beras Kencur (Kaempferia galanga and Oryza sativa) and Kunyit Asam (Curcuma longa and Tamarindus indica) act at this mucosal interface. Objective: To delineate the multi-target systems pharmacology of Jamu phytomolecules across the gut-liver axis. Methods: Fecal shotgun metagenomes (BioProject PRJNA737472; N = 180: 60 healthy controls, 60 non-alcoholic fatty liver and 60 MASH) were profiled with MetaPhlAn 4 and HUMAnN 3. Community flux balance analysis of a four-species commensal consortium was performed in AGORA2 using COBRApy, and molecular docking was run in AutoDock Vina 1.2.0 against tight junction, innate immune and nuclear receptor targets. Results: Faecalibacterium prausnitzii (−77.4%) and Akkermansia muciniphila (−83.5%) were depleted in MASH (both p < 0.001), together with the SCFA biosynthetic genes but (−58.4%), pct (−46.2%) and ackA (−38.7%). Jamu supplementation restored acetate cross-feeding and raised community butyrate secretion by 84.6% (0.422 to 0.779 mmol/gDW/h). Ethyl p-methoxycinnamate bound the Toll-like receptor 4/myeloid differentiation factor 2 complex (ΔG = −8.84 kcal/mol; inhibition constant, Ki = 0.33 µM), curcumin bound Occludin (ΔG = −8.92 kcal/mol) and demethoxycurcumin bound zonula occludens-1 (ΔG = −8.45 kcal/mol). Barrier reinforcement reduced modeled portal LPS influx by 68%. Conclusion: Beras Kencur and Kunyit Asam restore commensal SCFA cross-feeding, reinforce the mucosal barrier and attenuate endotoxin-driven hepatic inflammation in MASH.
Co-Authors Adolfo Rawlings Dedi Sucipto Ericca Dominique Perez Louisa Istarini Louisa Istarini Mischa Chantal Adella