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      KCI등재 SCOPUS SCIE

      State-of-the-Art Overview of the Pharmacological Treatment of Non-Alcoholic Steatohepatitis

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      https://www.riss.kr/link?id=A108042644

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      다국어 초록 (Multilingual Abstract)

      Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, can progress to cirrhosis, hepatocellular carcinoma, and death. Nevertheless, the curr...

      Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, can progress to cirrhosis, hepatocellular carcinoma, and death. Nevertheless, the current treatment for NAFLD/NASH is limited to lifestyle modifications, and no drugs are currently officially approved as treatments for NASH. Many global pharmaceutical companies are pursuing the development of medications for the treatment of NASH, and results from phase 2 and 3 clinical trials have been published in recent years. Here, we review data from these recent clinical trials and reports on the efficacy of newly developed antidiabetic drugs in NASH treatment.

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      참고문헌 (Reference)

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      4 Vuppalanchi R, "Therapeutic pipeline in nonalcoholic steatohepatitis" 18 : 373-392, 2021

      5 Safadi R, "The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease" 12 : 2085-2091, 2014

      6 Latva-Rasku A, "The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity : a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients" 42 : 931-937, 2019

      7 Madaan T, "Sodium glucose CoTransporter 2(SGLT2)inhibitors : current status and future perspective" 93 : 244-252, 2016

      8 Junker A, "Selective and dual targeting of CCR2 and CCR5 receptors : a current overview" 14 : 187-241, 2015

      9 Gawrieh S, "Saroglitazar, a PPAR-α/γ agonist, for treatment of NAFLD : a randomized controlled double-blind phase 2 trial" 74 : 1809-1824, 2021

      10 Lucas KJ, "Safety and efficacy of tropifexor in patients with fibrotic nonalcoholic steatohepatitis : 48-week results from part C of the phase 2 flight-FXR study" 72 (72): 101A-102A, 2020

      1 Frias JP, "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes" 385 : 503-515, 2021

      2 Soccio RE, "Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes" 20 : 573-591, 2014

      3 Degirolamo C, "Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23" 15 : 51-69, 2016

      4 Vuppalanchi R, "Therapeutic pipeline in nonalcoholic steatohepatitis" 18 : 373-392, 2021

      5 Safadi R, "The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease" 12 : 2085-2091, 2014

      6 Latva-Rasku A, "The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity : a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients" 42 : 931-937, 2019

      7 Madaan T, "Sodium glucose CoTransporter 2(SGLT2)inhibitors : current status and future perspective" 93 : 244-252, 2016

      8 Junker A, "Selective and dual targeting of CCR2 and CCR5 receptors : a current overview" 14 : 187-241, 2015

      9 Gawrieh S, "Saroglitazar, a PPAR-α/γ agonist, for treatment of NAFLD : a randomized controlled double-blind phase 2 trial" 74 : 1809-1824, 2021

      10 Lucas KJ, "Safety and efficacy of tropifexor in patients with fibrotic nonalcoholic steatohepatitis : 48-week results from part C of the phase 2 flight-FXR study" 72 (72): 101A-102A, 2020

      11 Abdul-Ghani MA, "Role of sodium-glucose cotransporter 2(SGLT 2)inhibitors in the treatment of type 2 diabetes" 32 : 515-531, 2011

      12 Softic S, "Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease" 61 : 1282-1293, 2016

      13 Iruarrizaga-Lejarreta M, "Role of aramchol in steatohepatitis and fibrosis in mice" 1 : 911-927, 2017

      14 Boland ML, "Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist cotadutide via modulating mitochondrial function and lipogenesis" 2 : 413-431, 2020

      15 Harrison SA, "Resmetirom(MGL-3196)for the treatment of non-alcoholic steatohepatitis : a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial" 394 : 2012-2024, 2019

      16 Traber PG, "Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease" 8 : e75361-, 2013

      17 Ali AH, "Recent advances in the development of farnesoid X receptor agonists" 3 : 5-, 2015

      18 Harrison SA, "Randomised clinical study : GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis" 44 : 1183-1198, 2016

      19 Harrison SA, "RESOLVE-IT® phase 3 trial of elafibranor in NASH: final results of the week 72 interim surrogate efficacy analysis" 2020

      20 Sanyal AJ, "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis" 362 : 1675-1685, 2010

      21 ClinicalTrials.gov, "Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)" NIH

      22 Grygiel-Gorniak B, "Peroxisome proliferator-activated receptors and their ligands : nutritional and clinical implications : a review" 13 : 17-, 2014

      23 Sanyal A, "Pegbelfermin(BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis : a randomised, double-blind, placebo-controlled, phase 2a trial" 392 : 2705-2717, 2019

      24 Ratziu V, "One-year results of the global phase 2b randomized placebo-controlled ARREST trial of aramchol, a stearoyl CoA desaturase inhibitor, in patients with NASH" 68 : 1448-, 2018

      25 Younossi ZM, "Obeticholic acid for the treatment of non-alcoholic steatohepatitis : interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial" 394 : 2184-2196, 2019

      26 Sinha RA, "Nonalcoholic fatty liver disease and hypercholesterolemia : roles of thyroid hormones, metabolites, and agonists" 29 : 1173-1191, 2019

      27 이용호 ; 조용인 ; 이병완 ; 박철영 ; 이대호 ; 차봉수 ; 이은정, "Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis" 대한당뇨병학회 43 (43): 31-45, 2019

      28 Adams LA, "Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases" 66 : 1138-1153, 2017

      29 한유진 ; 이용호, "Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases" 대한당뇨병학회 41 (41): 430-437, 2017

      30 이병완 ; 이용호 ; 박철영 ; 이은정 ; 이원영 ; 김난희 ; 최경묵 ; 박근규 ; 최연경 ; 차봉수 ; 이대호 ; The Korean Diabetes Association (KDA) Fatty Liver Research Group, "Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association" 대한당뇨병학회 44 (44): 382-401, 2020

      31 NGM Bio, "NGM Bio Reports Topline Results from 24-Week Phase 2b ALPINE 2/3 Study of Aldafermin in NASH" NGM Biopharmaceuticals

      32 Tilg H, "NAFLD and diabetes mellitus" 14 : 32-42, 2017

      33 Marra F, "Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis" 14 : 72-81, 2008

      34 Metacrine, "Metacrine demonstrates best-in-class FXR drug program with positive clinical results in NASH patients" Metacrine

      35 Miller ER 3rd, "Meta-analysis : high-dosage vitamin E supplementation may increase all-cause mortality" 142 : 37-46, 2005

      36 Eslam M, "MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease" 158 : 1999-2014, 2020

      37 Cusi K, "Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus : a randomized trial" 165 : 305-315, 2016

      38 Armstrong MJ, "Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis(LEAN) : a multicentre, double-blind, randomised, placebo-controlled phase 2 study" 387 : 679-690, 2016

      39 Loomba R, "LBP-20-VK2809, a novel liver-directed thyroid receptor beta agonist, significantly reduces liver fat with both low and high doses in patients with non-alcoholic fatty liver disease : a phase 2 randomized, placebo-controlled trial" 70 : e150-e151, 2019

      40 Intercept Pharmaceuticals, "Intercept receives complete response letter from FDA for obeticholic acid for the treatment of fibrosis due to NASH" GlobeNewswire

      41 Harrison SA, "Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis : a randomized, double-blind, placebo-controlled phase IIb study" 72 : 613-626, 2020

      42 Chen J, "Insights into the Role of PPARβ/δ in NAFLD" 19 : 1893-, 2018

      43 Wu Z, "Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids" 16 : 4128-4136, 1996

      44 Sanchez RA, "Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease" 6 : 1186-1197, 2015

      45 Gupta NA, "Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway" 51 : 1584-1592, 2010

      46 Younossi Z, "Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis" 69 : 2672-2682, 2019

      47 Loomba R, "GS-0976 reduces hepatic steatosis and fibrosis markers in patients with nonalcoholic fatty liver disease" 155 : 1463-1473, 2018

      48 Gastaldelli A, "From NASH to diabetes and from diabetes to NASH : mechanisms and treatment options" 1 : 312-328, 2019

      49 Carr RM, "FXR agonists as therapeutic agents for non-alcoholic fatty liver disease" 17 : 500-, 2015

      50 Kahl S, "Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes : a randomized, double-blind, phase 4, placebo-controlled trial" 43 : 298-305, 2020

      51 Guirguis E, "Emerging therapies for the treatment of nonalcoholic steatohepatitis : a systematic review" 41 : 315-328, 2021

      52 Ratziu V, "Elafibranor, an agonist of the peroxisome proliferator-activated receptor-α and-δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening" 150 : 1147-1159, 2016

      53 Harrison SA, "Efruxifermin in non-alcoholic steatohepatitis : a randomized, double-blind, placebo-controlled, phase 2a trial" 27 : 1262-1271, 2021

      54 Frias JP, "Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes : a 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens" 22 : 938-946, 2020

      55 Harrison SA, "Efficacy and safety of aldafermin, an engineered FGF19 analog, in a randomized, double-blind, placebo-controlled trial of patients with nonalcoholic steatohepatitis" 160 : 219-231, 2021

      56 Rosenstock J, "Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes(SURPASS-1) : a double-blind, randomised, phase 3 trial" 398 : 143-155, 2021

      57 Eriksson JW, "Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes : a double-blind randomised placebo-controlled study" 61 : 1923-1934, 2018

      58 Nahra R, "Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes : a 54-week randomized phase 2b study" 44 : 1433-1442, 2021

      59 Chalasani N, "Effects of belapectin, an inhibitor of galectin-3, in patients with nonalcoholic steatohepatitis with cirrhosis and portal hypertension" 158 : 1334-1345, 2020

      60 Kuchay MS, "Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease : a randomized controlled trial(E-LIFT Trial)" 41 : 1801-1808, 2018

      61 Kuchay MS, "Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD : randomised controlled trial(D-LIFT trial)" 63 : 2434-2445, 2020

      62 Cusi K, "Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes" 21 : 812-821, 2019

      63 ENANTA Pharmaceuticals, "ENANTA announces positive results of ARGON-1 study of its lead FXR agonist, EDP-305, for the treatment of NASH" ENANTA Pharmaceuticals

      64 Ratziu V, "EDP-305 in patients with NASH : a phase II double-blind placebo-controlled dose-ranging study" 76 : 506-517, 2022

      65 Thiagarajan P, "Drug development for nonalcoholic fatty liver disease : landscape and challenges" 9 : 515-521, 2019

      66 Raza S, "Current treatment paradigms and emerging therapies for NAFLD/NASH" 26 : 206-237, 2021

      67 Leoni S, "Current guidelines for the management of non-alcoholic fatty liver disease : a systematic review with comparative analysis" 24 : 3361-3373, 2018

      68 Loomba R, "Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH" 73 : 625-643, 2021

      69 Patel K, "Cilofexor, a nonsteroidal FXR agonist, in patients with noncirrhotic NASH : a phase 2 randomized controlled trial" 72 : 58-71, 2020

      70 Makki K, "Adipose tissue in obesity-related inflammation and insulin resistance : cells, cytokines, and chemokines" 2013 : 139239-, 2013

      71 ClinicalTrials.gov, "AURORA: Phase 3 Study for the Efficacy and Safety of CVC for the Treatment of Liver Fibrosis in Adults With NASH" NIH

      72 Harrison SA, "A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis" 72 : 816-827, 2020

      73 Friedman SL, "A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis" 67 : 1754-1767, 2018

      74 Francque SM, "A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH" 385 : 1547-1558, 2021

      75 Newsome PN, "A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis" 384 : 1113-1124, 2021

      76 Fiorucci S, "A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis" 314 : 584-595, 2005

      77 ClinicalTrials.gov, "A Study to Evaluate Safety and Pharmacodynamic Efficacy of 0382 in Obese Subjects With NAFLD/NASH" NIH

      78 ClinicalTrials.gov, "A Study of Tirzepatide (LY3298176) in Participants With Nonalcoholic Steatohepatitis (NASH) (SYNERGY-NASH)" NIH

      79 ClinicalTrials.gov, "A Phase 3 Study to Evaluate the Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease (NAFLD) Patients (MAESTRO-NAFLD1)" NIH

      80 ClinicalTrials.gov, "A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis (MAESTRO-NASH)" NIH

      81 ClinicalTrials.gov, "A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR) (ARMOR)" NIH

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      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2013-12-16 학술지명변경 한글명 : 대한내분비학회지 -> Endocrinology and Metabolism
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      2013-01-01 평가 등재 1차 FAIL (등재유지) KCI등재
      2010-06-28 학술지명변경 외국어명 : Journal of Korean Endocrin Society -> Endocrinology and Metabolism KCI등재
      2010-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-06-05 학회명변경 영문명 : The Korean Society Of Endocrinology -> Korean Endocrin Society KCI등재
      2007-06-01 학술지명변경 외국어명 : Journal of Korean Society of Endocrinology -> Journal of Korean Endocrin Society KCI등재
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