Probiotics for NAFLD

Compounds that bind to the farnesoid X receptor (FXR) as agonists or modulators for treating diseases like cholestatic conditions, liver fibrosis, obesity, diabetes, metabolic disorders, inflammatory bowel disease, lipid disorders, stroke, thrombosis, infections, cancer, and liver steatosis. The compounds have structures with specific substituents on the aromatic ring and side chain. They can be used to develop drugs for treating these conditions by activating FXR signaling.

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A treatment for fatty liver disease and fibrotic liver disease, including alcoholic liver disease and non-alcoholic fatty liver disease, comprising a combination of fermented cereal composition and probiotic microorganisms, preferably anti-inflammatory Lactobacillus plantarum strains 299 and 299v. The treatment involves daily administration of a ready-to-use fermented cereal composition, which can be formulated with or without postbiotics such as short-chain fatty acids, to prevent disease progression, initiate regression, or postpone progression of liver disease.

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A compound, HK4, is disclosed for the treatment and prevention of non-alcoholic fatty liver disease (NAFLD) and related conditions. HK4 prevents palmitate-induced apoptosis in hepatocytes and potentiates GABA effects, reducing inflammation and cell death associated with NAFLD progression. The compound is administered in a therapeutically effective amount to alleviate NAFLD symptoms and prevent disease progression.

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A method for treating or preventing non-alcoholic steatohepatitis (NASH) using a thyroid hormone receptor-β (THR-β) agonist, such as resmetirom, which reduces liver inflammation and fibrosis. The method involves administering the THR-β agonist to a subject with NASH, either as a standalone treatment or in combination with other therapies, to achieve a significant reduction in liver enzymes and fibrosis markers.

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A novel probiotic drug for preventing and treating metabolic diseases, comprising Nosocomiicoccus massiliensis, a Gram-positive bacterium isolated from hospital environments. The probiotic activates GPR120, MC4R, and APJ receptors, targets for obesity and diabetes treatment, and reduces body weight, blood sugar, and lipid metabolism indicators in obese mice.

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Combination therapy for treating metabolic diseases, comprising a PPAR full agonist and a THR-β agonist, which synergistically regulates lipid metabolism, insulin sensitivity, and liver function to improve conditions such as obesity, diabetes, hyperlipidemia, NASH, and chronic kidney disease.

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Pharmaceutical composition for preventing or treating alcoholic and non-alcoholic fatty liver disease, comprising ATPase inhibitory factor 1 (IF1) as an active ingredient. IF1, a human-derived protein, protects hepatocytes from alcohol toxicity, prevents lipid accumulation, suppresses liver fibrosis and inflammation, and modulates gut microbiota.

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Compositions and methods for inhibiting cell death-inducing DFFA-like effector B (CIDEB) gene expression, particularly for treating liver diseases such as nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). The compositions comprise double-stranded RNA (dsRNA) agents that specifically target CIDEB mRNA, and the methods involve administering these agents to inhibit CIDEB expression and treat associated diseases.

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A method of treating liver diseases such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by administering a double-stranded short interfering nucleic acid (siNA) molecule that targets the HSD17B13 gene. The siNA molecule comprises a sense strand and an antisense strand, each with a nucleotide sequence that is at least 60% identical to a corresponding sequence in the HSD17B13 gene. Administration of the siNA molecule reduces HSD17B13 expression in hepatocytes, thereby treating liver diseases.

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Engineering bacteria for preventing and treating non-alcoholic steatohepatitis (NASH) through genetic modification to produce polyphenolic compounds with therapeutic activity. The engineered bacteria, such as E. coli Nissle 1917, are designed to synthesize compounds like p-coumaric acid that have anti-inflammatory, fat-reducing, and insulin-resistance-improving effects. The bacteria are engineered to convert glucose into tyrosine and then into p-coumaric acid through heterologous expression of tyrosine aminotransferase. The engineered bacteria can be administered orally to treat NASH and maintain a sustained release of the therapeutic compound.

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siRNA for inhibiting CIDEB gene expression, comprising a sense strand and an antisense strand, wherein the sense strand and the antisense strand are complementary, and the sequence thereof is selected from any group of duplexes shown in Table 1 or at least 15 consecutive nucleotide sequences that differ from the duplexes by no more than 3 nucleotides. The siRNA is used to treat diseases associated with CIDEB expression, including hepatitis, liver fibrosis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, alcoholic steatohepatitis (ASH), alcoholic fatty liver disease (ALD), HCV-related cirrhosis, drug-induced liver damage and hepatocellular necrosis.

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Peptides derived from the SOCS1 protein inhibit the JAK/STAT signaling pathway to prevent and treat non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The peptides, which are cell-permeable and can be administered orally, reduce liver inflammation, fibrosis, and metabolic dysfunction in animal models of NAFLD. They specifically target the JAK/STAT pathway, which is dysregulated in NAFLD, and have been shown to prevent the progression of NAFLD to NASH and cirrhosis.

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A pyridazinone compound with thyroid hormone receptor beta (TRβ) agonist activity for treating metabolic disorders such as non-alcoholic steatohepatitis (NASH), obesity, atherosclerosis, and hyperlipidemia. The compound selectively activates TRβ receptors without the cardiac stimulation and bone resorption side effects associated with thyroid hormone replacement therapy. It has a novel chemical structure that combines a pyridazinone core with a specific aniline and triazine moiety, providing improved selectivity and pharmacokinetic properties compared to existing TRβ agonists.

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Methods for treating metabolic diseases and disorders using thyroid hormone receptor agonists that selectively activate thyroid hormone receptor beta (THRβ) without suppressing the thyroid hormone axis. The compounds, which include novel chemical entities, are designed to modulate lipid metabolism, reduce liver fat content, and prevent or treat nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) without affecting thyroid function or circulating thyroid hormone levels.

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A synbiotic composition for treating non-alcoholic fatty liver disease (NAFLD) comprising a prebiotic phytonutrient fibre material prepared from sugarcane and at least one probiotic bacterial strain. The prebiotic fibre material is derived from virgin sugarcane with the sugar removed, and the probiotic strain is selected for its ability to survive gastric transit and generate beneficial fermentation products. The synbiotic composition is administered in a food product or therapeutic formulation to modulate gut microbiota and reduce inflammation associated with NAFLD.

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Microorganism that can be used in the preparation of health foods or drugs for the prevention and treatment of non-alcoholic fatty liver disease. The microorganism includes Akermansia muciniphila, a probiotic combination product, and pharmaceutical excipients.

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Methods of treating and preventing liver diseases, including non-alcoholic steatohepatitis (NASH) and liver fibrosis, by administering a combination of an acetyl-CoA carboxylase (ACC) inhibitor and a farnesoid X receptor (FXR) agonist. The combination reduces liver damage, fibrosis, and inflammation, and can be used to treat various liver diseases, including NASH, liver fibrosis, and primary sclerosing cholangitis (PSC).

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Polymorphs of the SSAO inhibitor Compound I, including Form II, which exhibits improved stability and crystallinity compared to the known Form I. The polymorphs are prepared through controlled crystallization methods, such as evaporation of a solvent mixture or addition of an anti-solvent, and are useful in the treatment of liver disorders, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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Treatment of non-alcoholic fatty liver disease (NAFLD) by administering a compound that reduces expression of HSD17B13, a protein involved in lipid metabolism, through RNA interference. The compound is a double-stranded oligonucleotide linked to a ligand, administered at a dose of 25-200 mg, and repeated every 4-12 weeks. The treatment reduces HSD17B13 mRNA and protein levels by at least 50% and 30%, respectively, as measured by qRT-PCR and Western Blot.

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A composition for treating inflammatory diseases comprising live Adlercreutzia bacteria, particularly Adlercreutzia equolifaciens, and/or culture extracts thereof. The composition is used to prevent or treat inflammatory diseases such as non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel diseases (IBD) by modulating the gut microbiota and reducing inflammation.

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A Lactobacillus delbrueckii subsp. lactis strain, designated CKDB001, and a composition comprising the same for prevention or treatment of non-alcoholic fatty liver disease (NAFLD). The strain, isolated from human digestive systems, exhibits beneficial properties in alleviating NAFLD and associated inflammation. The composition, which may include a Bifidobacterium strain, is administered orally to prevent or treat NAFLD through modulation of the gut microbiota.

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Methods and compositions for treating liver disorders, including non-alcoholic steatohepatitis (NASH), using a thyroid hormone receptor-beta (THR-β) agonist, Compound 1, or a pharmaceutically acceptable salt thereof. The compound is administered at low doses to treat liver disorders without the undesirable side effects associated with thyroid hormone receptor-alpha (THR-α) agonism. The treatment is effective in reducing liver damage, inflammation, and fibrosis, and can be used to impede or slow the progression of non-alcoholic fatty liver disease (NAFLD) to NASH.

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Methods and compositions for treating liver disease, including non-alcoholic steatohepatitis (NASH), by administering a selective semicarbazide-sensitive amine oxidase (SSAO) inhibitor, such as Compound 1, to reduce liver fibrosis and inflammation. The SSAO inhibitor selectively inhibits SSAO without affecting monoamine oxidases A and B, and is effective in treating liver disorders including NASH, NAFLD, and liver fibrosis in patients with or without liver transplant history.

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A pharmaceutical composition for preventing or treating nonalcoholic fatty liver disease (NAFLD) comprising a G protein-coupled receptor 119 (GPR119) agonist and at least one additional drug with a different mechanism of action, such as a PPAR agonist, DPPIV inhibitor, ACC inhibitor, FXR agonist, or CCR2/5 dual antagonist. The composition is effective in treating NAFLD through mechanisms including inhibition of triglyceride accumulation, inflammation, and fibrosis in liver tissues.

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A medicament for preventing or treating non-alcoholic fatty liver disease (NAFLD) comprising Pulsatilla saponin B4 as the active ingredient, which effectively reduces lipid accumulation in the liver of rats induced by high-fat diet, and exhibits comparable efficacy to the positive control drug fenofibrate without hepatotoxic side effects.

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Compositions and methods for inhibiting angiopoietin-like 3 (ANGPTL3) protein expression using single-stranded (ssRNA) and double-stranded (dsRNA) RNA interference (RNAi) agents, including GalNAc-conjugated siRNA, to treat diseases and conditions associated with ANGPTL3, such as hyperlipidemia, atherosclerosis, and nonalcoholic steatohepatitis. The RNAi agents specifically target ANGPTL3 mRNA for degradation, reducing protein expression and modulating lipid metabolism.

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Use of resmetirom, a liver-directed thyroid hormone receptor beta agonist, for reducing liver volume in subjects with nonalcoholic steatohepatitis (NASH) and cirrhosis, and for treating or preventing NASH, portal hypertension, and other liver diseases.

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Probiotics and their metabolites (postbiotics) formulation for alleviating metabolic syndrome, comprising a mixture of Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus acidophilus, and Bifidobacterium lactis strains and their fermentation products, which inhibit fat accumulation, promote fat decomposition, improve insulin sensitivity, and alleviate fatty liver.

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A method of treating liver diseases such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by administering short interfering nucleic acid (siNA) molecules that target the HSD17B13 gene. The siNA molecules comprise optimized combinations and numbers of modified nucleotides, nucleotide lengths, design, and modification patterns that exhibit improved delivery and stability. The siNA molecules downregulate expression of the HSD17B13 gene, which is significantly up-regulated in the liver of patients with NAFLD and NASH and enhances lipogenesis.

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A peptide that activates F1-ATPase, a key enzyme in reverse cholesterol transport, for treating metabolic syndrome, cardiovascular disease, non-alcoholic fatty liver disease, and cholestatic liver disease. The peptide, derived from the inhibitory factor 1 (IF1) protein, has at least 70% sequence identity to the amino acid sequence of IF1 and can be modified with acetylation, amidation, PEGylation, or fatty acid conjugation to enhance stability and cell permeability.

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Pharmaceutical compositions and methods for treating liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), comprising a compound of formula (I) or a salt thereof, and optionally one or more additional therapeutic agents. The compositions and methods are effective in reducing liver fat, inflammation, and fibrosis, and improving liver function and overall health outcomes in patients with NAFLD and NASH.

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Lactobacillus plantarum HG-23, a novel probiotic strain, has been isolated and identified for its ability to reduce blood lipids. The strain exhibits significant cholesterol-lowering and triglyceride-reducing effects in animal models, making it a potential component for functional foods and pharmaceuticals targeting hyperlipidemia.

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siRNA and siRNA conjugates targeting type 13 17β-hydroxysteroid dehydrogenase (HSD17B13) for treating nonalcoholic steatohepatitis (NASH) and other liver diseases. The siRNAs specifically silence HSD17B13 expression, which is associated with liver inflammation and fibrosis. The siRNA conjugates are designed for targeted delivery to the liver, where they can effectively reduce HSD17B13 levels and prevent disease progression.

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Non-invasive biomarkers and methods for diagnosing and treating non-alcoholic fatty liver disease (NAFLD). The biomarkers include Lactococcus lactis and Dorea sp. 5-2, which are negatively associated with NAFLD, particularly with significant liver steatosis. The biomarkers can be detected through metagenomic analysis, quantitative PCR, or catalase activity tests. The invention also provides compositions and methods for treating NAFLD using fecal microbiota transplantation (FMT) or probiotics containing Lactococcus lactis and/or Dorea sp. 5-2.

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Novel lactic acid bacterium Lactococcus lactis subsp. lactis L8 strain isolated from Amur cork in the Shirakami Mountains, exhibiting blood glucose level reducing, lipid metabolism improving, antioxidant, antiobesity, fatty liver suppressing, hepatitis preventing, and intestinal environment improving actions. The strain can be cultured in a medium comprising glucose, ammonium sulfate, and beef extract or yeast extract, without peptones, and can be used as a dietary supplement or ingredient in functional foods.

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A novel strain of Lactobacillus fermentum that can prevent and treat cardiovascular diseases, obesity, diabetes mellitus, and fatty liver disease. The strain reduces inflammation in subcutaneous fat, blood glucose and insulin levels, and liver fat accumulation. It also lowers CRP, neutral fat, and cholesterol in blood.

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Thyroid hormone receptor beta (THR beta) agonist compounds for treating non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), metabolic syndrome, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. The compounds selectively activate THR beta over THR alpha, avoiding hyperthyroidism and hypothyroidism side effects, and are administered in therapeutically effective amounts of less than 5 mg/kg/day.

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A composition for preventing or treating fatty liver and metabolic syndrome comprising Lactococcus chungangensis as an active ingredient. The composition includes a strain of Lactococcus chungangensis, a culture of the strain, or a fermented product of the strain. The composition can be used as a pharmaceutical or food product to prevent or treat fatty liver and metabolic syndrome by reducing obesity, improving insulin resistance, and preserving liver function.

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A composition for preventing, alleviating, or treating liver injury, comprising a Ruminococcus spp. strain, particularly Ruminococcus faecis, which has been shown to have therapeutic effects in animal models of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis. The composition can be administered orally or through other routes, and can be formulated in various forms such as tablets, capsules, or injections. The Ruminococcus spp. strain can be cultured using a medium comprising carbon and nitrogen sources, and can be freeze-dried with protective agents to enhance stability.

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A novel crystalline form of resmetirom, a thyroid hormone receptor beta agonist, with improved solubility and bioavailability compared to existing forms. The crystal form 3 exhibits enhanced dissolution in fasted state simulated intestinal fluid (FaSSIF) and is suitable for pharmaceutical applications, including treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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Compositions comprising monounsaturated fatty acids (MUFAs) with low melting points and high iodine values for treating liver diseases, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The MUFAs have a melting point temperature of about -1.7°C to 10.7°C and an iodine value of 50 to 130. The compositions can be administered orally at a daily dose of 0.01 to 2 g/kg body weight for at least 8 weeks to treat or prevent liver disease.

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A health food composition and pharmaceutical composition for improving liver function, comprising a Lactobacillus pentosus KF8, Bacillus subtilis KF11, or Lactococcus lactis KF140 strain, or a lysate or culture product thereof. The composition inhibits liver damage indicators, reduces liver fat accumulation, and normalizes liver enzyme levels.

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Thyroid hormone receptor beta (THRβ) selective agonists for treating metabolic disorders, comprising compounds of formula (I) and their pharmaceutical compositions. The compounds selectively activate THRβ, mimicking the beneficial effects of thyroid hormones while avoiding hyperthyroidism and hypothyroidism. They are useful for treating obesity, hyperlipidemia, hypercholesterolemia, diabetes, non-alcoholic fatty liver disease (NASH), hepatic steatosis, atherosclerosis, and thyroid function disorders.

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Therapeutic use of cell-free fat extract for nonalcoholic steatohepatitis (NASH) treatment, comprising administering a cell-free fat extract to prevent and/or treat NASH, characterized by improved hepatic steatosis, reduced hepatocyte ballooning, and decreased liver inflammatory cell infiltration.

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Methods for treating liver diseases by inhibiting hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) activity. The methods involve administering a therapeutically effective amount of an HSD17B13 inhibitor to a subject in need thereof, thereby reducing liver injury and inflammation associated with conditions such as non-alcoholic steatohepatitis, alcoholic liver disease, viral hepatitis, and cholestatic diseases. The inhibitors can be small molecule compounds, antibodies, or oligonucleotides that specifically target HSD17B13.

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Polymorphs of 6-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid, a potent FXR agonist for treating liver disorders, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The polymorphs exhibit improved stability and manufacturability compared to the known form, enabling large-scale production and pharmaceutical development. The compounds selectively target liver tissue, reducing off-target effects and potentially mitigating pruritus, a common side effect of FXR agonists.

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A 6-oxo-1,6-dihydropyridazine derivative represented by the general formula (I) or its tautomer, racemate, enantiomer, diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, for use as a selective thyroid hormone receptor beta (THRβ) agonist for treating and preventing metabolic diseases regulated by thyroid hormones, including obesity, diabetes, hyperlipidemia, thyroid disease, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease.

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Prevention and treatment of dysbiosis caused by deficiencies or adverse changes in mammalian gut microbiota. The technology focuses on identifying and treating specific microbial species and their products that are critical for host health, particularly those that provide essential metabolic functions. The approach involves administering probiotics that contain these critical microbes, as well as their metabolic precursors and products, to restore balance and function in the gut microbiome. This enables the recovery of critical microbial species and their metabolic pathways that are essential for normal host health, including detoxification processes, neurotransmitter synthesis, and other physiological functions.

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A method for mitigating non-alcoholic fatty liver disease (NAFLD) using a composition comprising small-molecule fucoidan and fucoxanthin. The composition is administered to subjects with NAFLD, resulting in significant improvements in liver function, fibrosis, and metabolic parameters, including reductions in liver stiffness, alanine aminotransferase (ALT) levels, and glycated hemoglobin (HbA1c) levels, as well as increases in pancreatic β-cell function.

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Solid dispersions of the FXR agonist 6-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid (Compound I) for improved pharmacokinetic properties in treating liver disorders. The solid dispersions comprise Compound I dispersed in a polymer, preferably a hydrophilic polymer such as a vinyl lactam homopolymer or copolymer, and are prepared by hot-melt extrusion. The solid dispersions exhibit enhanced solubility and bioavailability compared to the free compound, enabling effective treatment of liver disorders including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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