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©The Author(s) 2023.
World J Hepatol. Jan 27, 2023; 15(1): 19-40
Published online Jan 27, 2023. doi: 10.4254/wjh.v15.i1.19
Published online Jan 27, 2023. doi: 10.4254/wjh.v15.i1.19
Table 2 Therapeutic interventions implicated in acute and chronic liver disorders
Therapeutic intervention | Drugs | Main findings | Ref. |
Antioxidants | Silymarin | Possesses free radical scavenging activity and inhibits lipid peroxidation thus improving chronic liver diseases | [149] |
Selenium | Decrease DNA damage, hepatocyte necrosis, oxidative stress biomarkers, and liver toxicity | ||
Vitamin E | Reduces inflammation and protects from hepatocellular damage | [155,157,160] | |
N acetylcysteine | Increasing GSH peroxidase and decreasing oxidative stress in liver fibrosis | ||
MitoQ | Reduces lipid peroxidation and cultured hepatic stellate cell activation | [162] | |
Antifibrotic agents | Pirfenidone | Pirfenidone is effective at diminishing liver fibrosis as it suppresses TGF-β1 and NF-κB and decreases inflammatory cell infiltration and excess matrix deposition | [166-168] |
Statins, and anti- NADPH oxidases | PPAR-α modulators might decrease inflammation and fibrosis in cases of primary sclerosing cholangitis | ||
Immunosuppressants | Corticosteroids, and azathioprine | The first line of treatment for autoimmune hepatitis | [169] |
Anti-HSC therapy | Imatinib and sorafenib | Respectively act as PDGF and angiogenesis inhibitors thus they modulate fibrogenesis and fibrosis in autoimmune hepatitis | [173] |
Paclitaxel, ferulic acid and methyl ferulic acid | Can inhibit hepatic stellate cell activation through TGF-β/Smad pathway modulation | [175-177] | |
Curcumin | Can interrupt the PDGF-β/ERK pathway and inhibit hepatic stellate cell angiogenesis through activation of PPAR-γ. Curcumin can also activate autophagy and thus inhibit the TGF-β/Smad pathway thus reducing epithelial-mesenchymal transition | [178-180] | |
Gene therapy | HGF | Decreases the expression of TGF-β1, suppresses hepatocyte apoptosis, and improves fibrosis | [181] |
Matrix metalloproteinase-1 | Enhances the proliferation of hepatocytes and diminishes fibrosis | [183] | |
siRNA | By silencing CTGF, TGF-β, NF-κB target gene A, galectin-3, and αvβ3 integrin, siRNA effectively stops fibrogenesis by preventing HSCs activation and/or promoting their apoptosis | [184] | |
Cell therapy | MSCs | Inhibit hepatocyte degeneration, promote liver regeneration, and suppress fibrosis through differentiation into hepatocytes and production of various growth factors | [187] |
BMSCs | Decrease serum markers of liver injury and mRNA expression of TNF-α, IFN-γ, and FasL, and increase IL-10 mRNA expression in acute liver failure | [189] | |
Matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1, and growth arrest-specific 6 | Promote hepatocytes regeneration, neovascularization, and extracellular matrix remodeling all contributing to liver regeneration | [191] | |
Gut liver axis | Baicalin | Modulates FXR and G-protein-coupled bile acid receptor TGR5 thus modulating the levels of TNF-α, NF-kβ, and TGF-β. It also inhibits inflammation, autophagy, and necrosis of parenchymal liver cells | [195-198] |
Probiotics | Modulate gut dysbiosis and bile acid dysregulation thus aiding in the treatment of NAFLD. Probiotics also modulate inflammation and fibrosis in NASH | [199-201] | |
Nanoparticle drug delivery | Gold | Enhances the antifibrotic activity of silymarin through increasing the expression of protective microRNAs and suppression of inflammatory mediators in the TGF-β1/smad pathway | [204] |
Phosphatidylserine-decorated nanoparticles | Enhances curcumin efficacy in fibrosis reduction | [205] | |
Liposome nanoparticles | Can be specifically delivered to integrins of activated hepatic stellate cells, in addition to facilitating gene therapy using siRNAs and mRNAs to modulate gene expression of hepatocytes | [208] | |
Autophagy inhibition | Becn1 knockdown | Autophagy suppression and inhibition of T lymphocyte infiltration, HSCs proliferation, as well as production of TNF-α, IFN-γ, and TGF-β1 | [209] |
Carvedilol | Increased p62 protein levels and inhibited autophagic flux by increasing lysosomal pH | [210] | |
Doxazosin | Inhibited HSC proliferation and migration, blocked autophagic flux and induced HSCs apoptosis | [211] | |
Resolvin D1 | Modulated AKT/mTOR signaling pathway resulting in the inhibition of autophagy and suppression of hepatic stellate cell activation | [212,213] |
- Citation: Ali FE, Abd El-Aziz MK, Sharab EI, Bakr AG. Therapeutic interventions of acute and chronic liver disorders: A comprehensive review. World J Hepatol 2023; 15(1): 19-40
- URL: https://www.wjgnet.com/1948-5182/full/v15/i1/19.htm
- DOI: https://dx.doi.org/10.4254/wjh.v15.i1.19