Anti-fibrotic Therapy for Chronic Liver Diseases Review

Maged Naser, Mohamed M. Naser, Lamia H. Shehata

Abstract


Liver fibrosis reflects tissue scarring in the liver because of the accumulation of over the top extracellular matrix in light of constantly persistent liver injury. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells including macrophages and Kupffer cells, and initiation of hepatic stellate cells (HSCs), bringing about progression of liver fibrosis. Liver cirrhosis is the terminal condition of liver fibrosis and is related with serious complications, like liver failure, portal hypertension, and liver malignant growth. In any case, compelling treatment for cirrhosis has not yet been set up, and liver transplantation is the main revolutionary treatment for severe cases. Studies examining HSC activation and guideline of collagen creation in the liver have made leap forwards in ongoing many years that have advanced the information with respect to liver fibrosis pathophysiology. In this review, we sum up molecular mechanisms of liver fibrosis and discuss the improvement of novel anti- fibrotic treatments.


Keywords


Fibrosis; Hepatic stellate cells; Myofibroblasts; Extracellular matrix; Drug therapy

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References


-Asrani, Sumeet K., et al. "Burden of liver diseases in the world." Journal of hepatology 70.1 (2019): 151-171.

- European Association for The Study of the Liver. "EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis." Journal of hepatology 69.2 (2018): 406-460.

- Ni, Yao, et al. "Pathological process of liver sinusoidal endothelial cells in liver diseases." World journal of gastroenterology 23.43 (2017): 7666.

- Pimpin, Laura, et al. "Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies." Journal of hepatology 69.3 (2018): 718-735.

- Iredale, John P. "Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ." The Journal of clinical investigation 117.3 (2007): 539-548.

-Friedman, Scott L. "Mechanisms of hepatic fibrogenesis." Gastroenterology 134.6 (2008): 1655-1669.

- Tsuchida, Takuma, and Scott L. Friedman. "Mechanisms of hepatic stellate cell activation." Nature reviews Gastroenterology & hepatology 14.7 (2017): 397-411.

- Wynn, Thomas A. "Common and unique mechanisms regulate fibrosis in various fibro proliferative diseases." The Journal of clinical investigation 117.3 (2007): 524-529.

- Geervliet, Eline, and Ruchi Bansal. "Matrix metalloproteinases as potential biomarkers and therapeutic targets in liver diseases." Cells 9.5 (2020): 1212.

- Marcellin, Patrick, et al. "Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study." The Lancet 381.9865 (2013): 468-475.

- Chang, Ting‐Tsung, et al. "Long‐term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B." Hepatology 52.3 (2010): 886-893.

- D'Ambrosio, Roberta, et al. "A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis." Hepatology 56.2 (2012): 532-543.

- Vilar-Gomez, Eduardo, et al. "Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis." Gastroenterology 149.2 (2015): 367-378.

- Maher, Jacquelyn J., et al. "Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer." The Journal of clinical investigation 82.2 (1988): 450-459.

- Kawada, Norifumi, Heike Klein, and Karl Decker. "Eicosanoid-mediated contractility of hepatic stellate cells." Biochemical Journal 285.2 (1992): 367-371.

- Pinzani, M., et al. "Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients." The Journal of clinical investigation 90.2 (1992): 642-646.

- Koyama, Yukinori, and David A. Brenner. "Liver inflammation and fibrosis." The Journal of clinical investigation 127.1 (2017): 55-64.

- Seki, Ekihiro, et al. "TLR4 enhances TGF-β signalling and hepatic fibrosis." Nature medicine 13.11 (2007): 1324-1332.

- Liu, Cheng, et al. "Transcriptional repression of the transforming growth factor β (TGF-β) Pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) by Nuclear Factor κB (NF-κB) p50 enhances TGF-β signalling in hepatic stellate cells." Journal of Biological Chemistry 289.10 (2014): 7082-7091.

- Yang, Liu, et al. "Regulation of peroxisome proliferator-activated receptor-γ in liver fibrosis." American Journal of Physiology-Gastrointestinal and Liver Physiology 291.5 (2006): G902-G911.

- Sanyal, Arun J., et al. "Pioglitazone, vitamin E, or placebo for non-alcoholic steatohepatitis." New England Journal of Medicine 362.18 (2010): 1675-1685.

- Musso, Giovanni, et al. "Thiazolidinediones and advanced liver fibrosis in non-alcoholic steatohepatitis: a meta-analysis." JAMA internal medicine 177.5 (2017): 633-640.

- Staels, Bart, et al. "Hepatoprotective effects of the dual peroxisome proliferator‐activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis." Hepatology 58.6 (2013): 1941-1952.

- Ratziu, Vlad, et al. "Elafibranor, an agonist of the peroxisome proliferator− activated receptor− α and− δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening." Gastroenterology 150.5 (2016): 1147-1159.

- Odagiri, Naoshi, et al. "Anti-fibrotic treatments for chronic liver diseases: The present and the future." Clinical and Molecular Hepatology 27.3 (2021): 413.

- Rotman, Yaron, and Arun J. Sanyal. "Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease." Gut 66.1 (2017): 180-190.

-Rotman, Yaron, and Arun J. Sanyal. "Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease." Gut 66.1 (2017): 180-190.

- Mudaliar, Sunder, et al. "Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease." Gastroenterology 145.3 (2013): 574-582.

- Younossi, Zobair M., et al. "Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial." The Lancet 394.10215 (2019): 2184-2196.

- Odagiri, Naoshi, et al. "Anti-fibrotic treatments for chronic liver diseases: The present and the future." Clinical and Molecular Hepatology 27.3 (2021): 413.

- Nishikawa, Koji, Yosuke Osawa, and Kiminori Kimura. "Wnt/β-catenin signaling as a potential target for the treatment of liver cirrhosis using antifibrotic drugs." International Journal of Molecular Sciences 19.10 (2018): 3103.

- Tokunaga, Yuko, et al. "Selective inhibitor of Wnt/β-catenin/CBP signalling ameliorates hepatitis C virus-induced liver fibrosis in mouse model." Scientific reports 7.1 (2017): 1-11.

- Kimura, Kiminori, et al. "Safety, tolerability, and preliminary efficacy of the anti-fibrotic small molecule PRI-724, a CBP/β-catenin inhibitor, in patients with hepatitis C virus-related cirrhosis: a single-center, open-label, dose escalation phase 1 trial." EBioMedicine 23 (2017): 79-87.

- Kimura, Kiminori, et al. "Safety, tolerability, and preliminary efficacy of the anti-fibrotic small molecule PRI-724, a CBP/β-catenin inhibitor, in patients with hepatitis C virus-related cirrhosis: a single-center, open-label, dose escalation phase 1 trial." EBioMedicine 23 (2017): 79-87.

- Altenhöfer, Sebastian, et al. "The NOX toolbox: validating the role of NADPH oxidases in physiology and disease." Cellular and Molecular Life Sciences 69.14 (2012): 2327-2343.

- Drummond, Grant R., et al. "Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets." Nature reviews Drug discovery 10.6 (2011): 453-471.

- Jiang, Joy X., et al. "Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo." Free Radical Biology and Medicine 53.2 (2012): 289-296.

- Paik, Yong‐Han, et al. "The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91phox mediate hepatic fibrosis in mice." Hepatology 53.5 (2011): 1730-1741.

- Aoyama, Tomonori, et al. "Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent." Hepatology 56.6 (2012): 2316-2327.

-Rossignol, Jean-François. "Nitazoxanide: a first-in-class broad-spectrum antiviral agent." Antiviral research 110 (2014): 94-103.

- Belanger, Carole, et al. "Drug repurposing screen identifies novel small molecule compounds with potent antifibrotic properties." J Hepatol 66 (2017): S605.

- Belanger, Carole, et al. "Drug repurposing screen identifies novel small molecule compounds with potent antifibrotic properties." J Hepatol 66 (2017): S605.

- Burmester, Thorsten, et al. "Cytoglobin: a novel globin type ubiquitously expressed invertebrate tissues." Molecular biology and evolution 19.4 (2002): 416-421.

- Burmester, Thorsten, et al. "Cytoglobin: a novel globin type ubiquitously expressed invertebrate tissues." Molecular biology and evolution 19.4 (2002): 416-421.

- Le Thi Thanh Thuy, Hoang Hai, and Norifumi Kawada. "Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis." Clinical and Molecular Hepatology 26.3 (2020): 280.

- Okina, Yoshinori, et al. "TGF-β1-driven reduction of cytoglobin leads to oxidative DNA damage in stellate cells during non-alcoholic steatohepatitis." Journal of hepatology 73.4 (2020): 882-895.

- Morita, Takashi, et al. "Promotion of liver and lung tumorigenesis in DEN-treated cytoglobin-deficient mice." The American journal of pathology 179.2 (2011): 1050-1060.

- Li, Zhen, et al. "The effect of rhCygb on CCl 4-induced hepatic fibrogenesis in rat." Scientific reports 6.1 (2016): 1-11.

- Sato-Matsubara, Misako, et al. "Fibroblast growth factor 2 (FGF2) regulates cytoglobin expression and activation of human hepatic stellate cells via JNK signaling." Journal of Biological Chemistry 292.46 (2017): 18961-18972.

- Issa, R., et al. "Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors." Gut 48.4 (2001): 548-557.

- Watson, Martha R., et al. "NF-κB is a critical regulator of the survival of rodent and human hepatic myofibroblasts." Journal of hepatology 48.4 (2008): 589-597.

- Zhang, Yuwei, et al. "Vitamin A-coupled liposomes carrying TLR4-silencing shRNA induce apoptosis of pancreatic stellate cells and resolution of pancreatic fibrosis." Journal of Molecular Medicine 96.5 (2018): 445-458.

- Ezhilarasan, Devaraj, Etienne Sokal, and Mustapha Najimi. "Hepatic fibrosis: It is time to go with hepatic stellate cell-specific therapeutic targets." Hepatobiliary & Pancreatic Diseases International 17.3 (2018): 192-197.

- Barry-Hamilton, Vivian, et al. "Allosteric inhibition of lysyl oxidase–like-2 impedes the development of a pathologic microenvironment." Nature medicine 16.9 (2010): 1009-1017.

- Liu, Susan B., et al. "Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice." The FASEB Journal 30.4 (2016): 1599-1609.

-Rodriguez, Hector M., et al. "Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric antibody inhibitor." Journal of Biological Chemistry 285.27 (2010): 20964-20974.

- Harrison, Stephen A., et al. "Simtuzumab is ineffective for patients with bridging fibrosis or compensated cirrhosis caused by nonalcoholic steatohepatitis." Gastroenterology 155.4 (2018): 1140-1153.

- Muir, Andrew J., et al. "Simtuzumab for primary sclerosing cholangitis: phase 2 study results with insights on the natural history of the disease." Hepatology 69.2 (2019): 684-698.

-Karsdal, Morten Asser, et al. "The good and the bad collagens of fibrosis–their role in signaling and organ function." Advanced drug delivery reviews 121 (2017): 43-56.

- Jiménez Calvente, Carolina, et al. "Specific hepatic delivery of procollagen α1 (I) small interfering RNA in lipid‐like nanoparticles resolves liver fibrosis." Hepatology 62.4 (2015): 1285-1297.

- Molokanova, Olena, et al. "Inducible knockdown of procollagen I protect mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation." Matrix Biology 66 (2018): 34-49.

- Tasab, Mohammed, Margaret R. Batten, and Neil J. Bulleid. "Hsp47: a molecular chaperone that interacts with and stabilizes correctly‐folded procollagen." The EMBO journal 19.10 (2000): 2204-2211.

- Ito, Shinya, and Kazuhiro Nagata. "Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone." Seminars in cell & developmental biology. Vol. 62. Academic Press, 2017.

- Sato, Yasushi, et al. "Resolution of liver cirrhosis using vitamin A–coupled liposomes to deliver siRNA against a collagen-specific chaperone." Nature biotechnology 26.4 (2008): 431-442.

- Odagiri, Naoshi, et al. "Anti-fibrotic treatments for chronic liver diseases: The present and the future." Clinical and Molecular Hepatology 27.3 (2021): 413.

- Schwabe, Robert F., Ramón Bataller, and David A. Brenner. "Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration." American Journal of Physiology-Gastrointestinal and Liver Physiology 285.5 (2003): G949-G958.

- Seki, Ekihiro, et al. "CCR1 and CCR5 promote hepatic fibrosis in mice." The Journal of clinical investigation 119.7 (2009): 1858-1870.

-Seki, Ekihiro, et al. "CCR2 promotes hepatic fibrosis in mice." Hepatology 50.1 (2009): 185-197.

- Mitchell, Claudia, et al. "Dual role of CCR2 in the constitution and the resolution of liver fibrosis in mice." The American journal of pathology 174.5 (2009): 1766-1775.

- Berres, Marie-Luise, et al. "Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice." The Journal of clinical investigation 120.11 (2010): 4129-4140.

-Karlmark, Karlin Raja, et al. "Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis." Hepatology 50.1 (2009): 261-274.

- Miura, Kouichi, et al. "Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2." American Journal of Physiology-Gastrointestinal and Liver Physiology 302.11 (2012): G1310-G1321.

- Pradere, Jean‐Philippe, et al. "Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice." Hepatology 58.4 (2013): 1461-1473.

- Lefebvre, Eric, et al. "Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis." PloS one 11.6 (2016): e0158156.

- Mossanen, Jana C., et al. "Chemokine (C‐C motif) receptor 2–positive monocytes aggravate the early phase of acetaminophen‐induced acute liver injury." Hepatology 64.5 (2016): 1667-1682.

- Friedman, Scott L., et al. "A randomized, placebo‐controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis." Hepatology 67.5 (2018): 1754-1767.

- Pedrosa, Marcos, et al. "A randomized, double-blind, multicenter, phase 2b study to evaluate the safety and efficacy of a combination of tropifexor and cenicriviroc in patients with nonalcoholic steatohepatitis and liver fibrosis: study design of the TANDEM trial." Contemporary clinical trials 88 (2020): 105889.

- Yang, Ri-Yao, DANIEL K. Hsu, and Fu-Tong Liu. "Expression of galectin-3 modulates T-cell growth and apoptosis." Proceedings of the National Academy of Sciences 93.13 (1996): 6737-6742.

-Jeng, Kee Ching G., Luciano G. Frigeri, and Fu-Tong Liu. "An endogenous lectin, galectin-3 (ϵBP/Mac-2), potentiates IL-1 production by human monocytes." Immunology letters 42.3 (1994): 113-116.

- Sano, Hideki, et al. "Human galectin-3 is a novel chemoattractant for monocytes and macrophages." The Journal of Immunology 165.4 (2000): 2156-2164.

- Traber, Peter G., and Eliezer Zomer. "Therapy of experimental NASH and fibrosis with galectin inhibitors." PloS one 8.12 (2013): e83481.

- Traber, Peter G., et al. "Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease." PloS one 8.10 (2013): e75361.

- Chalasani, Naga, et al. "Effects of belapectin, an inhibitor of galectin-3, in patients with nonalcoholic steatohepatitis with cirrhosis and portal hypertension." Gastroenterology 158.5 (2020): 1334-1345.

- Strowig, Till, et al. "Inflammasomes in health and disease." nature 481.7381 (2012): 278-286.

- Szabo, Gyongyi, and Timea Csak. "Inflammasomes in liver diseases." Journal of hepatology 57.3 (2012): 642-654.

- Gross, Olaf, et al. "The inflammasome: an integrated view." Immunological reviews 243.1 (2011): 136-151.

- Calvente, Carolina Jimenez, et al. "Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223." The Journal of clinical investigation 129.10 (2019): 4091-4109.

- Thapaliya, Samjhana, et al. "Caspase 3 inactivation protects against hepatic cell death and ameliorates fibrogenesis in a diet-induced NASH model." Digestive diseases and sciences 59.6 (2014): 1197-1206.

- Philips, George M., et al. "Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer." PloS one 6.9 (2011): e23943.

- Garcia-Tsao, Guadalupe, et al. "Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension." Journal of hepatology 72.5 (2020): 885-895.

- Harrison, Stephen A., et al. "A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis." Journal of hepatology 72.5 (2020): 816-827.

- Kim, Kyeongjin, and Kook Hwan Kim. "Targeting of secretory proteins as a therapeutic strategy for treatment of nonalcoholic steatohepatitis (NASH)." International journal of molecular sciences 21.7 (2020): 2296.

-Yamamoto, Eiichiro, et al. "Olmesartan prevents cardiovascular injury and hepatic steatosis in obesity and diabetes, accompanied by apoptosis signal regulating kinase-1 inhibition." Hypertension 52.3 (2008): 573-580.

- Wang, Pi-Xiao, et al. "Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates." Nature medicine 23.4 (2017): 439-449.

- Sumida, Yoshio, and Masashi Yoneda. "Current and future pharmacological therapies for NAFLD/NASH." Journal of gastroenterology 53.3 (2018): 362-376.

- Loomba, Rohit, et al. "The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial." Hepatology 67.2 (2018): 549-559.

- Harrison, Stephen A., et al. "Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials." Journal of hepatology 73.1 (2020): 26-39.

- Luedde, Tom, et al. "Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma." Cancer cell 11.2 (2007): 119-132.

-Luedde, Tom, et al. "Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury." The Journal of clinical investigation 115.4 (2005): 849-859.

- Yang, Y. M., and E. Seki. "TNFalpha in liver fibrosis. Curr Pathobiol Rep 3: 253–261." (2015).

- Canbay, Ali, et al. "Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression." Hepatology 38.5 (2003): 1188-1198.

- Canbay, Ali, Scott Friedman, and Gregory J. Gores. "Apoptosis: the nexus of liver injury and fibrosis." Hepatology 39.2 (2004): 273-278.

- Noble, Paul W., et al. "Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials." The Lancet 377.9779 (2011): 1760-1769.

-King Jr, Talmadge E., et al. "A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis." New England Journal of Medicine 370.22 (2014): 2083-2092.

- Flores-Contreras, Lucia, et al. "Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C." BMC gastroenterology 14.1 (2014): 1-11.

- Komiya, Chikara, et al. "Antifibrotic effect of pirfenidone in a mouse model of human nonalcoholic steatohepatitis." Scientific reports 7.1 (2017): 1-12.

- Poo, Jorge Luis, et al. "Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study." Hepatology International 14.5 (2020): 817-827.

- Kharitonenkov, Alexei, and Philip Larsen. "FGF21 reloaded: challenges of a rapidly growing field." Trends in Endocrinology & Metabolism 22.3 (2011): 81-86.

- Charles, Edgar D., et al. "Pegbelfermin (BMS‐986036), PEGylated FGF21, in patients with obesity and type 2 diabetes: results from a randomized phase 2 study." Obesity 27.1 (2019): 41-49.

-Itoh, Nobuyuki. "FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases." Frontiers in endocrinology 5 (2014): 107.

- Sanyal, Arun, et al. "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." The Lancet 392.10165 (2018): 2705-2717

- Pose, Elisa, et al. "Statins: old drugs as new therapy for liver diseases?" Journal of hepatology 70.1 (2019): 194-202.

- Dongiovanni, Paola, et al. "Statin use and non-alcoholic steatohepatitis in at risk individuals." Journal of hepatology 63.3 (2015): 705-712.

- Nascimbeni, Fabio, et al. "Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease." BMJ open gastroenterology 3.1 (2016): e000075.

- Guaraldi, Giovanni, et al. "New drugs for NASH and HIV infection: great expectations for a great need." Hepatology 71.5 (2020): 1831-1844.

- Safadi, Rifaat, et al. "The fatty acid–bile acid conjugate aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease." Clinical Gastroenterology and Hepatology 12.12 (2014): 2085-2091.

- Sinha, Rohit A., et al. "Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists." Thyroid 29.9 (2019): 1173-1191.

- Zucchi, Riccardo. "Thyroid hormone analogues: An update." Thyroid 30.8 (2020): 1099-1105.

- Luong, Xuan G., et al. "Regulation of gene transcription by thyroid hormone receptor β agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH)." Plos one 15.12 (2020): e0240338.

- Harrison, Stephen A., et al. "Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial." The Lancet 394.10213 (2019): 2012-2024.

- Kliewer, Steven A., and David J. Mangelsdorf. "Bile acids as hormones: the FXR-FGF15/19 pathway." Digestive diseases 33.3 (2015): 327-331.

- Alisi, Anna, et al. "Association between serum atypical fibroblast growth factors 21 and 19 and pediatric nonalcoholic fatty liver disease." PloS one 8.6 (2013): e67160.

- Wojcik, Malgorzata, et al. "A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents." Journal of Pediatric Endocrinology and Metabolism 25.11-12 (2012): 1089-1093.

- Zhou, Mei, et al. "Separating tumorigenicity from bile acid regulatory activity for endocrine hormone FGF19." Cancer research 74.12 (2014): 3306-3316.

- Zhou, Mei, et al. "Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis." Nature communications 8.1 (2017): 1-16.

- Zhou, Mei, et al. "Engineered FGF19 eliminates bile acid toxicity and lipotoxicity leading to resolution of steatohepatitis and fibrosis in mice." Hepatology communications 1.10 (2017): 1024-1042.

- Harrison, Stephen A., et al. "NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial." The Lancet 391.10126 (2018): 1174-1185.

- Schiff, Eugene R., et al. "Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B." Clinical Gastroenterology and Hepatology 9.3 (2011): 274-276.

- Terrault, Norah A., et al. "A ASLD guidelines for treatment of chronic hepatitis B." Hepatology 63.1 (2016): 261-283.

- Akhtar, Ehsaan, Vignan Manne, and Sammy Saab. "Cirrhosis regression in hepatitis C patients with sustained virological response after antiviral therapy: a meta‐analysis." Liver International 35.1 (2015): 30-36.

- Bachofner, Jacqueline A., et al. "Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis‐4 score and aspartate aminotransferase‐platelet ratio index." Liver International 37.3 (2017): 369-376.

- Dolmazashvili, Ekaterine, et al. "Regression of liver fibrosis over a 24-week period after completing direct-acting antiviral therapy in patients with chronic hepatitis C receiving care within the national hepatitis C elimination program in Georgia: results of hepatology clinic HEPA experience." European journal of gastroenterology & hepatology 29.11 (2017): 1223-1230.

- Borssén, Åsa D., et al. "Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study." Medicine 96.34 (2017).

- Corpechot, Christophe, et al. "The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis." Hepatology 32.6 (2000): 1196-1199.




DOI: http://dx.doi.org/10.52155/ijpsat.v29.2.3730

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