Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key
Abstract
:1. Introduction
2. How to Phenotype NAFLD Patients
2.1. Histological Features
2.2. Metabolic Comorbidities
2.3. Weight
2.3.1. Obese Patients
2.3.2. Lean Patients
2.4. Cardiovascular Diseases
2.5. Inflammatory Dysfunction
2.6. Genetic Factors
2.7. Microbiome
2.8. Toxics Consumption
2.8.1. Alcohol
2.8.2. Drugs
2.9. Concomitant Infections
3. NAFLD Treatment
3.1. Treatments to Rule Them All
3.2. Targeted Therapy
3.2.1. Targeting Lipid Metabolism
3.2.2. Targeting Glucose Metabolism
Mechanism | Drug | Identifier | Intervention | Title | Status |
---|---|---|---|---|---|
Lipid metabolism | Lanifibranor | NCT04849728 | Drug: Lanifibranor|Drug: Placebo | A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 (NATiV3) | Recruiting |
Rosuvastatin | NCT05731596 | Drug: Rosuvastatin 20 mg Oral Tablet|Drug: Coenzyme Q10 100 mg Oral Capsule | Comparative Clinical Study to Evaluate the Efficacy and Safety of Rosuvastatin vs. CoQ10 on Non-alcoholic Steatohepatitis | Not yet recruiting | |
Oltipraz | NCT04142749 | Drug: Oltipraz|Drug: Placebos | Oltipraz for Liver Fat Reduction in Patients with Non-alcoholic Fatty Liver Disease Except for Liver Cirrhosis | Completed | |
NCT02068339 | Drug: Oltipraz 1 (90 mg)|Drug: Placebo|Drug: Oltipraz 2 (120 mg) | Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients with Non-alcoholic Fatty Liver Disease Except for Liver Cirrhosis | Completed | ||
Resmetirom | NCT03900429 | Drug: Resmetirom|Drug: Placebo | A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients with NASH and Fibrosis | Recruiting | |
NCT04197479 | Drug: Placebo|Drug: Resmetirom | A Phase 3 Study to Evaluate the Safety and Biomarkers of Resmetirom (MGL-3196) in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients | Active, not recruiting | ||
Glucose metabolism | Pioglitazone | NCT05521633 | Drug: Metformin and Pioglitazone | Comparison of the Effects of Metformin and Pioglitazone on Liver Enzymes and Ultrasound Changes in Non-Diabetic Non-alcoholic Fatty Liver | Completed |
NCT05605158 | Drug: Pioglitazone 30 mg|Drug: Empagliflozin 10 mg | Comparative Clinical Study Between Empagliflozin Versus Pioglitazone in Non-diabetic Patients with Non-alcoholic Steatohepatitis | Not yet recruiting | ||
NCT00063622 | Drug: Pioglitazone|Dietary Supplement: Vitamin E|Drug: Matching placebo | Pioglitazone vs. Vitamin E vs. Placebo for Treatment of Non-Diabetic Patients with Non-alcoholic Steatohepatitis (PIVENS) | Completed | ||
Semaglutide | NCT05067621 | Drug: Semaglutide Pen Injector|Drug: Placebo | Semaglutide Effects in Obese Youth with Prediabetes/New Onset Type 2 Diabetes and Non-alcoholic Fatty Liver Disease | Not yet recruiting | |
NCT03919929 | Drug: Semaglutide 3 mg and 7 mg [Rybelsus]|Other: Weight loss diet | Treating PCOS With Semaglutide vs. Active Lifestyle Intervention | Recruiting | ||
NCT04822181 | Drug: Semaglutide|Drug: Placebo | Research Study on Whether Semaglutide Works in People with Non-alcoholic Steatohepatitis (NASH) | Recruiting | ||
Exenatide | NCT00650546 | Drug: Exenatide | Role of Exenatide in NASH-a Pilot Study | Completed | |
Cotadutide | NCT05364931 | Drug: Cotadutide|Drug: Placebo | A Study to Evaluate the Safety and Efficacy of Cotadutide Given by Subcutaneous Injection in Adult Participants with Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis. | Active, not recruiting | |
Vildagliptin | NCT03925701 | Drug: Vildagliptin|Drug: vildagliptin\metformin | Clinical Study Evaluating Vildagliptin Versus Vildagliptin/Metformin on NAFLD With DM | Recruiting | |
Dapagliflozin | NCT05308160 | Drug: Dapagliflozin 10 mg Tab|Drug: Placebo | A Single Center, Randomized, Open Label, Parallel Group, Phase 3 Study to Evaluate the Efficacy of Dapagliflozin in Subjects with Non-alcoholic Fatty Liver Disease | Recruiting | |
NCT03723252 | Drug: Dapagliflozin|Drug: Placebo | Dapagliflozin Efficacy and Action in NASH | Recruiting | ||
Empagliflozin | NCT05605158 | Drug: Pioglitazone 30 mg|Drug: Empagliflozin 10 mg | Comparative Clinical Study Between Empagliflozin Versus Pioglitazone in Non-diabetic Patients with Non-alcoholic Steatohepatitis | Not yet recruiting | |
Bile acid metabolism | Obeticholic acid | NCT02548351 | Drug: Obeticholic Acid|Drug: Placebo | Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment | Active, not recruiting |
NCT03439254 | Drug: Obeticholic acid (10 mg)|Drug: Obeticholic acid (10 mg to 25 mg)|Drug: Placebo | Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects with Compensated Cirrhosis Due to Non-alcoholic Steatohepatitis | Completed | ||
Aramchol | NCT04104321 | Drug: Aramchol|Drug: Placebo | A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects with NASH (ARMOR) (ARMOR) | Suspended | |
Oxidative stress, inflammation and fibrosis | N-acetylcysteine | NCT05589584 | Drug: N acetyl cysteine with weight reduction | N-acetyl Cysteine and Patients with Non-alcoholic Fatty Liver Disease | Recruiting |
Pentoxifylline | NCT05284448 | Drug: pentoxifylline (Trental SR®) | Pentoxifylline in Treatment of Patients with Non-alcoholic Steatohepatitis | Active, not recruiting | |
NCT00267670 | Drug: Pentoxifylline|Drug: Placebo | Pentoxifylline/Non-alcoholic Steatohepatitis (NASH) Study: The Effect of Pentoxifylline on NASH | Completed | ||
Secukinumab | NCT04237116 | Biological: Investigational Arm—secukinumab|Biological: Control Arm—placebo | A Study of Secukinumab Treatment in Patients with Plaque Psoriasis and Coexisting Non-alcoholic Fatty Liver Disease (NAFLD) | Completed | |
Lubiprostone | NCT05768334 | Drug: Lubiprostone 24 Mcg Oral Cap | Efficacy and Tolerability of Lubiprostone in Patients with Non-alcoholic Fatty Liver Disease | Recruiting |
3.2.3. Targeting Bile Acid Metabolism
3.2.4. Targeting Oxidative Stress, Inflammation and Fibrosis
4. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | SNPs | Function | References |
---|---|---|---|
PNPLA3 | rs738409 | Lipid metabolism and inflammatory response | [70,71] |
rs6006460 | |||
MBOAT7 | rs641738 | Lipid metabolism | [72] |
HSD17B13 | rs72613567 | Lipid metabolism | [73] |
FTO | rs1421085 | Lipid metabolism and adipogenesis | [74] |
LPIN1 | rs13412852 | Lipid metabolism and adipogenesis | [75] |
TM6SF2 | rs58542926 | VLDL secretion | [76] |
LYPLAL1 | rs12137855 | Glucose homeostasis | [77] |
GCKR | rs780094 | Regulation of de novo lipogenesis and insulin resistance | [78,79] |
ENPP1 | rs1044498 | Insulin signaling inhibitor | [80] |
PPP1R3B | rs4240624 | Glycogen metabolism | [81] |
SOD2 | rs4880 | Fibrosis and oxidative stress | [82] |
MERTK | rs4374383 | Immune response | [83] |
FNDC5 | rs3480 | Liver fibrogenesis | [84] |
KLF6 | rs3750861 | Liver fibrogenesis | [85] |
CDKN1A | rs762623 | Cell senescence | [86] |
IL28B | rs12979860 | Inflammatory response | [87] |
Therapeutic Class | Drug/Group | References |
---|---|---|
Antiarrhythmics | Amiodarone | [126] |
Antibiotics | Tetracyclines | [127,128] |
Antidiabetics | Troglitazone | [129,130,131] |
Antiepileptics | Carbamazepine | [132] |
Valproic acid | [132,133,134] | |
Anti-inflammatories | Dexamethasone | [135] |
Antitumor drugs | 5-Fluorouracil | [136,137] |
Irinotecan | [137,138,139,140] | |
Leuprorelin acetate | [141] | |
Methotrexate | [142] | |
Tamoxifen | [143,144] | |
Antiretrovirals | Nucleoside Reverse Transcriptase Inhibitors | [145,146] |
Protease Inhibitors | [147] | |
Hormones | Estrogens | [148] |
Vasodilator agents | Perhexiline maleate | [149,150] |
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Alonso-Peña, M.; Del Barrio, M.; Peleteiro-Vigil, A.; Jimenez-Gonzalez, C.; Santos-Laso, A.; Arias-Loste, M.T.; Iruzubieta, P.; Crespo, J. Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key. Int. J. Mol. Sci. 2023, 24, 10718. https://doi.org/10.3390/ijms241310718
Alonso-Peña M, Del Barrio M, Peleteiro-Vigil A, Jimenez-Gonzalez C, Santos-Laso A, Arias-Loste MT, Iruzubieta P, Crespo J. Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key. International Journal of Molecular Sciences. 2023; 24(13):10718. https://doi.org/10.3390/ijms241310718
Chicago/Turabian StyleAlonso-Peña, Marta, Maria Del Barrio, Ana Peleteiro-Vigil, Carolina Jimenez-Gonzalez, Alvaro Santos-Laso, Maria Teresa Arias-Loste, Paula Iruzubieta, and Javier Crespo. 2023. "Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key" International Journal of Molecular Sciences 24, no. 13: 10718. https://doi.org/10.3390/ijms241310718