Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions
Abstract
:1. Liver Fibrosis Overview, Causes, and Burden
1.1. Alcoholic Liver Disease
1.2. Non-Alcoholic Fatty Liver Disease
1.3. Chronic Hepatitis C
1.4. Chronic Hepatitis B
2. Inflammation and Progression of Liver Fibrosis
2.1. Kupffer Cells and Liver Inflammation in Non-Alcoholic Fatty Liver Disease
2.2. T Cell-Mediated Inflammation in Autoimmune Hepatitis
2.3. Natural Killer and Natural Killer T Cell-Related Inflammation in Viral Hepatitis
2.4. Alternative Stem Cell Lines for the Treatment of Liver Cirrhosis: A Focus on Mesenchymal Stem Cells
3. Liver Fibrosis Therapies
3.1. Pre-Clinical Liver Fibrosis Treatments with MSCs
3.2. Clinical Translation of Liver Fibrosis Therapies with MSCs
3.3. Gene Delivery and Genetically Modified Stem Cells
3.4. Targeted Molecular Pathways and Small Molecule Drug Delivery
3.5. Monoclonal Antibodies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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General Category | Target Disease Condition | Therapeutic Agent | Responsible Company/Lab | Phase | ClinicalTrials.gov Identifier |
---|---|---|---|---|---|
Stem Cells | Compensated Liver Cirrhosis | Autologous Mesenchymal stem cells (MSCs) and Pioglitazone | Royan Institute | Phase I | NCT01454336 [84] |
Hepatitis C Virus (HCV) Infection | Autologous Mesenchymal stem cells (MSCs) | Saglik Bilimleri Universitesi Gulhane Tip Fakultesi | Phase I/II | NCT02705742 [91] | |
End-stage Liver Cirrhosis | Autograft MSCs Differentiated Into Progenitor of Hepatocytes | Shahid Beheshti University of Medical Sciences and Tarbiat Modarres University | Phase I/II | NCT00420134 [99] | |
Chronic liver insufficiency | Autologous Expanded CD34+ Haemopoietic cells | Imperial College London | Phase I/II | NCT00655707 [90] | |
Liver Cirrhosis | Co-transferring of MSCs and Tregs | Nanjing Medical University | Phase I/II | NCT03460795 [100] | |
Liver Cirrhosis | Autologous Bone Mesenchymal Stem Cells (bMSCs) via Portal Vein | Sun Yat-sen University | Phase II | NCT00993941 [88] | |
Acute-On-Chronic Liver Failure | Human umbilical cord-derived mesenchyme stem cells (hUC-MSCs) | Hai Li, Shanghai Jiao Tong University School of Medicine | Phase II | NCT04822922 [101] | |
Liver Cirrhosis, portal hypertension, hepatic Decompensation | Autologous bone marrow stem cells infusion (ABMSCi) and abdominal portal hypertension surgery | Wenzhou Medical University | Phase II/III | NCT01560845 [86] | |
Liver Cirrhosis | Intrahepatic Arterial Administration of Autologous Adipose Tissue Derived Stromal Cells | Kanazawa University | N/A | NCT01062750 [102] | |
Small Molecules | Chronic Hepatitis C Virus (HCV) | Small Molecule Agent (PF-868554), direct antiviral agent | Pfizer | Phase I | NCT00671671 [17] |
Chronic Hepatitis C Virus (HCV) Infection | Emricasan (IDN-6556) | Conatus Pharmaceuticals Inc. | Phase II | NCT02138253 [103] | |
Chronic Liver Fibrosis | Prolonged-Release Pirfenidone Formulation | Grupo Mexicano para el Estudios de las Enfermedades Hepaticas | Phase II | NCT04099407 [104] | |
Hepatic Fibrosis in Chronic Hepatitis C | Irbesartan | French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) and Sanofi | Phase III | NCT00265642 [105] | |
Hepatic Fibrogenesis in Chronic Hepatitis C | Losartan | Hospital Clinic of Barcelona | Phase IV | NCT00298714 [106] | |
Antibody Therapy | Alcoholic Liver Disease | Guselkumab, a humanized anti-IL23 monoclonal antibody | University of California, San Diego | Phase I | NCT04736966 [107] |
Non-alcoholic Fatty Acid Liver Disease | IMM-124E, polyclonal antibody against endotoxin lipopolysaccharide (LPS) | Immuron Ltd., Emory University, and Advanced MR Analytics AB | Phase II | NCT03042767 [108] | |
Diagnostic Tools | Liver Fibrosis and Congestion in Fontan Patients | Non-Contrast Magnetic Resonance Imaging, Device | Children’s Hospital Medical Center, Cincinnati | N/A | NCT03539757 [109] |
Liver Fibrosis | Mechanical Vibrations with Ultrasound Shear Wave Imaging, Device | Mayo Clinic | N/A | NCT03637959 [110] | |
Liver Fibrosis | Fibroscan® of Echosens, Aixplorer® of Supersonic Imagine, Aplio XG of Toshiba, QRS software developed by Pr I.Bricault, Acuson S2000 of Siemens, Device | University Hospital, Grenoble & Clinical Investigation Centre for Innovative Technology Network | N/A | NCT01537965 [111] |
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Neshat, S.Y.; Quiroz, V.M.; Wang, Y.; Tamayo, S.; Doloff, J.C. Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions. Int. J. Mol. Sci. 2021, 22, 6777. https://doi.org/10.3390/ijms22136777
Neshat SY, Quiroz VM, Wang Y, Tamayo S, Doloff JC. Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions. International Journal of Molecular Sciences. 2021; 22(13):6777. https://doi.org/10.3390/ijms22136777
Chicago/Turabian StyleNeshat, Sarah Y., Victor M. Quiroz, Yuanjia Wang, Sebastian Tamayo, and Joshua C. Doloff. 2021. "Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions" International Journal of Molecular Sciences 22, no. 13: 6777. https://doi.org/10.3390/ijms22136777