본문 바로가기
KERD
논문KCI 등재

Reversal of liver cirrhosis: current evidence and expectations

임형준|정영걸
대한내과학회 (The Korean Association Of Internal Medicine)|2017.03|The Korean Journal of Internal Medicine|제32권 제2호|pp. 213-228|DOI https://doi.org/10.3904/kjim.2016.268

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

TherapyReversalFibrosisLiver cirrhosisHepatic stellate cells
주제분류내과학

초록

In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis.

Abstract

In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis.

참고문헌 (132)

  1. 백수정, "Decreased S100B expression in chronic liver diseases", The Korean Journal of Internal Medicine, 32(2), pp.269~276 (2017), 대한내과학회[DOI]
  2. Friedman SL., "Mechanisms of hepatic fibrogenesis", Gastroenterology, 134, pp.1655~1669 (2008)
  3. Ueno T, "Hepatic stellate cells and intralobular innervation in human liver cirrhosis", Hum Pathol, 28, pp.953~959 (1997)
  4. Hellerbrand C, "The role of TGFbeta1 in initiating hepaticstellate cell activation in vivo", J Hepatol, 30, pp.77~87 (1999)
  5. Bataller R, "Liver fibrosis", J Clin Invest, 115, pp.209~218 (2005)
  6. Krizhanovsky V, "Senescence of activated stellate cells limits liver fibrosis", Cell, 134, pp.657~667 (2008)
  7. Mormone E, "Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches", Chem Biol Interact, 193, pp.225~231 (2011)
  8. Kupffer cells on stellate cells, "Hepatology", 2006, 1487~1501
  9. Kisseleva T, "Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis", J Gastroenterol Hepatol, 22(Suppl 1), pp.S73~S78 (2007)
  10. Sanz-Cameno P, "Enhanced intrahepatic inducible nitric oxide synthase expression and nitrotyrosine accumulation in primary biliary cirrhosis and autoimmune hepatitis", J Hepatol, 37, pp.723~729 (2002)
  11. Zhan SS, "Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo", Hepatology, 43, pp.435~443 (2006)
  12. Iwakiri Y., "Nitric oxide in liver fibrosis: the role of inducible nitric oxide synthase", Clin Mol Hepatol, 21, pp.319~325 (2015)
  13. De Minicis S, "NOX in liver fibrosis", Arch Biochem Biophys, 462, pp.266~272 (2007)
  14. Hayashi H, "Biological significance of local TGF-βactivation in liver diseases", Front Physiol, 3, pp.12~ (2012)
  15. Bataller R, "Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II", Gastroenterology, 125, pp.117~125 (2003)
  16. Wasmuth HE, "CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis", Hepatology, 45, pp.543~544 (2007)
  17. Julien B, "Antifibrogenic role of the cannabinoid receptor CB2 in the liver", Gastroenterology, 128, pp.742~755 (2005)
  18. Marra F, "Adipokines in liver diseases", Hepatology, 50, pp.957~969 (2009)
  19. Bomble M, "Analysis of antigen-presenting functionality of cultured rat hepatic stellate cells and transdifferentiated myofibroblasts", Biochem Biophys Res Commun, 396, pp.342~347 (2010)
  20. Schuppan D, "Evolving therapies for liver fibrosis", J Clin Invest, 123, pp.1887~1901 (2013)
  21. Thabut D, "Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new targets for the treatment of portal hypertension?", J Hepatol, 53, pp.976~980 (2010)
  22. Muhanna N, "Amelioration of hepatic fibrosis by NK cell activation", Gut, 60, pp.90~98 (2011)
  23. Tiggelman AM, "Interleukin-6 production by human liver (myo)fibroblasts in culture: evidence for a regulatory role of LPS, IL-1 beta and TNF alpha", J Hepatol, 23, pp.295~306 (1995)
  24. Schwabe RF, "Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration", Am J Physiol Gastrointest Liver Physiol, 285, pp.G949~G958 (2003)
  25. Li Z, "Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease", Hepatology, 37, pp.343~350 (2003)
  26. Wasmuth HE, "Chemokines in liver inflammation and fibrosis", Semin Liver Dis, 30, pp.215~225 (2010)
  27. Jiang JX, "Reduced nicotinamide adenine dinucleotide phosphate oxidase 2 plays a key role in stellate cell activation and liver fibrogenesis in vivo", Gastroenterology, 139, pp.1375~1384 (2010)
  28. Jiang JX, "Apoptotic body engulfment by hepatic stellate cells promotes their survival by the JAK", STAT and Akt, J Hepatol, pp.2009, 51[DOI]
  29. Jeong WI, "Suppression of innate immunity (natural killer cell", interferon-γ) in the advanced stages of liver fibrosis in mice, 2011, pp.53, 1342~1351
  30. Hellerbrand, "Expression of intracellular adhesion molecule 1 by activated hepatic stellate cells", Hepatology, 24, pp.670~676 (1996)
  31. Knittel T, "Expression and regulation of cell adhesion molecules by hepatic stellate cells (HSC) of rat liver: involvement of HSC in recruitment of inflammatory cells during hepatic tissue repair", Am J Pathol, 154, pp.153~167 (1999)
  32. Wynn TA, "Mechanisms of fibrosis:therapeutic translation for fibrotic disease", Nat Med, 18, pp.1028~1040 (2012)
  33. Wilson MS, "Pulmonary fibrosis: pathogenesis, etiology and regulation", Mucosal Immunol, 2, pp.103~121 (2009)
  34. Wynn TA, "An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection", Nature, 376, pp.594~596 (1995)
  35. Marra F, "Mononuclear cells in liver fibrosis", Semin Immunopathol, 31, pp.345~358 (2009)
  36. Zimmermann HW, "Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis", PLoS One, 5, pp.e11049~ (2010)
  37. Duffield JS, "Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair", J Clin Invest, 115, pp.56~65 (2005)
  38. Miura K, "Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2", Am J Physiol Gastrointest Liver Physiol, 302, pp.G1310~G1321 (2012)
  39. Kisseleva T, "The phenotypic fate and functional role for bone marrow-derived stem cells in liver fibrosis", J Hepatol, 56, pp.965~972 (2012)
  40. Albillos A, "Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance", J Hepatol, 61, pp.1385~1396 (2014)
  41. Ubeda M, "Critical role of the liver in the induction of systemic inflammation in rats with preascitic cirrhosis", Hepatology, 52, pp.2086~2095 (2010)
  42. Kubes P, "Sterile inflammation in the liver", Gastroenterology, 143, pp.1158~1172 (2012)
  43. Song Y, "Autophagy in hepatic fibrosis", Biomed Res Int, 2014, pp.436242~ (2014)
  44. Senoo H, "Hepatic stellate cell (vitamin A-storing cell) and its relative:past, present and future", Cell Biol Int, 34, pp.1247~1272 (2010)
  45. Thoen LF, "A role for autophagy during hepatic stellate cell activation", J Hepatol, 55, pp.1353~1360 (2011)
  46. Gressner AM, "Induction of rat liver parenchymal cell apoptosis by hepatic myofibroblasts via transforming growth factor beta", Hepatology, 23, pp.571~581 (1996)
  47. Gressner AM, "Molecular mechanisms of liver fibrogenesis: a homage to the role of activated fat-storing cells", Digestion, 56, pp.335~346 (1995)
  48. Derynck R, "Smad-dependent and Smad-independent pathways in TGF-beta family signalling", Nature, 425, pp.577~584 (2003)
  49. Latella G, "Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in mice", Liver Int, 29, pp.997~1009 (2009)
  50. Dooley S, "Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage", Gastroenterology, 135, pp.642~659 (2008)
  51. Garzon R, "Targeting microRNAs in cancer: rationale, strategies and challenges", Nat Rev Drug Discov, 9, pp.775~789 (2010)
  52. Noetel A, "MicroRNA are central players in anti- and profibrotic gene regulation during liver fibrosis", Front Physiol, 3, pp.49~ (2012)
  53. Roderburg C, "Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis", Hepatology, 53, pp.209~218 (2011)
  54. Lakner AM, "Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis", Hepatology, 56, pp.300~310 (2012)
  55. Guimaraes EL, "Advanced glycation end products induce production of reactive oxygen species via the activation of NADPH oxidase in murine hepatic stellate cells", J Hepatol, 52, pp.389~397 (2010)
  56. Benyon RC, "Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver", Gastroenterology, 110, pp.821~831 (1996)
  57. Iredale JP, "Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors", J Clin Invest, 102, pp.538~549 (1998)
  58. Murphy FR, "Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis", J Biol Chem, 277, pp.11069~11076 (2002)
  59. Iredale J., "Defining therapeutic targets for liver fibrosis:exploiting the biology of inflammation and repair", Pharmacol Res, 58, pp.129~136 (2008)
  60. Iredale JP, "Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis", Hepatology, 24, pp.176~184 (1996)
  61. Issa R, "Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking", Gastroenterology, 126, pp.1795~1808 (2004)
  62. Parsons CJ, "Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats", Hepatology, 40, pp.1106~1115 (2004)
  63. Fallowfield JA, "Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis", J Immunol, 178, pp.5288~5295 (2007)
  64. Pellicoro A, "Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis", Hepatology, 55, pp.1965~1975 (2012)
  65. Tacke F, "Macrophage heterogeneity in liver injury and fibrosis", J Hepatol, 60, pp.1090~1096 (2014)
  66. Jiao J, "Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression", Hepatology, 55, pp.244~255 (2012)
  67. Mallat A, "Reversion of hepatic stellate cell to a quiescent phenotype: from myth to reality?", J Hepatol, 59, pp.383~386 (2013)
  68. Troeger JS, "Deactivation of hepatic stellate cells during liver fibrosis resolution in mice", Gastroenterology, 143, pp.1073~1083 (2012)
  69. Kisseleva T, "Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis", Proc Natl Acad Sci U S A, 109, pp.9448~9453 (2012)
  70. Pellicoro A, "Liver fibrosis and repair: immune regulation of wound healing in a solid organ", Nat Rev Immunol, 14, pp.181~194 (2014)
  71. Ellis EL, "Clinical evidence for the regression of liver fibrosis", J Hepatol, 56, pp.1171~1180 (2012)
  72. van Zonneveld M, "Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: no additional benefit of combination with lamivudine", Liver Int, 26, pp.399~405 (2006)
  73. Dienstag JL, "Histological outcome during long-term lamivudine therapy", Gastroenterology, 124, pp.105~117 (2003)
  74. Chang TT, "Long-term entecavir therapy results in the reversal of fibrosis", cirrhosis and continued histological improvement in patients with chronic hepatitis B, 2010, pp.52, 886~893
  75. Marcellin P, "Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study", Lancet, 381, pp.468~475 (2013)
  76. George SL, "Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients", Hepatology, 49, pp.729~738 (2009)
  77. Verrill C, "Alcohol-related cirrhosis: early abstinence is a key factor in prognosis, even in the most severe cases", Addiction, 104, pp.768~774 (2009)
  78. Sanyal AJ, "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis", N Engl J Med, 362, pp.1675~1685 (2010)
  79. Czaja AJ, "Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis", J Hepatol, 40, pp.646~652 (2004)
  80. Mohamadnejad M, "Impact of immunosuppressive treatment on liver fibrosis in autoimmune hepatitis", Dig Dis Sci, 50, pp.547~551 (2005)
  81. Colmenero J, "Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C", Am J Physiol Gastrointest Liver Physiol, 297, pp.G726~G734 (2009)
  82. McHutchison J, "Farglitazar lacks antifibrotic activity in patients with chronic hepatitis C infection", Gastroenterology, 138, pp.1365~1373 (2010)
  83. Kim MY, "Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated alcoholic liver fibrosis: a randomized open-label controlled study", Liver Int, 32, pp.977~987 (2012)
  84. Aithal GP, "Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis", Gastroenterology, 135, pp.1176~1184 (2008)
  85. Ratziu V, "Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial", Hepatology, 51, pp.445~453 (2010)
  86. Zein CO, "Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial", Hepatology, 54, pp.1610~1619 (2011)
  87. Ratziu V, "A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis", J Hepatol, 54, pp.1011~1019 (2011)
  88. Neuschwander-Tetri BA, "Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial", Lancet, 385, pp.956~965 (2015)
  89. Poupon RE, "Ursodiol for the longterm treatment of primary biliary cirrhosis: the UDCA-PBC Study Group", N Engl J Med, 330, pp.1342~1327 (1994)
  90. Corpechot C, "The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis", Hepatology, 32, pp.1196~1199 (2000)
  91. Korean Association for the Study of the Liver., "KASL clinical practice guidelines: management of chronic hepatitis B", Clin Mol Hepatol, 22, pp.18~75 (2016)
  92. Liaw YF., "Reversal of cirrhosis: an achievable goal of hepatitis B antiviral therapy", J Hepatol, 59, pp.880~881 (2013)
  93. Papatheodoridis GV, "Impact of interferon-alpha therapy on liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B", J Viral Hepat, 12, pp.199~206 (2005)
  94. Chang XM, "Effects of interferon-alpha on expression of hepatic stellate cell and transforming growth factor-beta1 and alpha-smooth muscle actin in rats with hepatic fibrosis", World J Gastroenterol, 11, pp.2634~2636 (2005)
  95. Weng H, "IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads", J Hepatol, 46, pp.295~303 (2007)
  96. Fung J, "Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study", J Viral Hepat, 18, pp.e200~e205 (2011)
  97. Kim SU, "Non-invasive assessment of changes in liver fibrosis via liver stiffness measurement in patients with chronic hepatitis B: impact of antiviral treatment on fibrosis regression", Hepatol Int, 4, pp.673~680 (2010)
  98. Shin SK, "Improvement of liver function and non-invasive fibrosis markers in hepatitis B virus-associated cirrhosis: 2 years of entecavir treatment", J Gastroenterol Hepatol, 30, pp.1775~1781 (2015)
  99. 여인구, "The factor that improve liver stiffness in patients with chronic hepatitis B", Clinical and Molecular Hepatology, 21(1), pp.32~40 (2015), 대한간학회
  100. Everson GT., "Management of cirrhosis due to chronic hepatitis C", J Hepatol, 42(Suppl), pp.S65~S74 (2005)
  101. Veldt BJ, "Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis", Ann Intern Med, 147, pp.677~684 (2007)
  102. Jacqueline A. Bachofner, "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), pp.369~376 (2017), Wiley-Blackwell[DOI]
  103. Rambaldi A, "Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis", Cochrane Database Syst Rev, (2), pp.CD002148~ (2005)
  104. Musso G, "A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease", Hepatology, 52, pp.79~104 (2010)
  105. Promrat K, "Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis", Hepatology, 51, pp.121~129 (2010)
  106. Neuschwander-Tetri BA., "Targeting the FXR nuclear receptor to treat liver disease", Gastroenterology, 148, pp.704~706 (2015)
  107. Roberts SK, "Prognosis of histological cirrhosis in type 1 autoimmune hepatitis", Gastroenterology, 110, pp.848~857 (1996)
  108. Czaja AJ, "Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis", Gastroenterology, 139, pp.58~72 (2010)
  109. Czaja AJ., "Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis", Aliment Pharmacol Ther, 39, pp.385~406 (2014)
  110. Karlsen TH, "Review article:controversies in the management of primary biliary cirrhosis and primary sclerosing cholangitis", Aliment Pharmacol Ther, 39, pp.282~301 (2014)
  111. Lindor KD, "Primary biliary cirrhosis", Hepatology, 50, pp.291~308 (2009)
  112. Goulis J, "Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis", Lancet, 354, pp.1053~1060 (1999)
  113. Gong Y, "Ursodeoxycholic acid for primary biliary cirrhosis", Cochrane Database Syst Rev, (3), pp.CD000551~ (2008)
  114. Prince MI, "Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort", Gut, 53, pp.865~870 (2004)
  115. Kaplan MM, "A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results", Hepatology, 39, pp.915~923 (2004)
  116. Corpechot C., "Primary biliary cirrhosis and bile acids", Clin Res Hepatol Gastroenterol, 36(Suppl 1), pp.S13~S20 (2012)
  117. Hirschfield GM, "Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid", Gastroenterology, 148, pp.751~761 (2015)
  118. Bacon BR, "Diagnosis and management of hemochromatosis: 2011practice guideline by the American Association for the Study of Liver Diseases", Hepatology, 54, pp.328~343 (2011)
  119. Falize L, "Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases", Hepatology, 44, pp.472~477 (2006)
  120. Mehal WZ, "Antifibrotic therapies in the liver", Semin Liver Dis, 35, pp.184~198 (2015)
  121. Patsenker E, "Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression", Gastroenterology, 135, pp.660~670 (2008)
  122. Wang Q, "Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease", Fibrogenesis Tissue Repair, 4, pp.4~ (2011)
  123. Giannone FA, "Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis", Lab Invest, 92, pp.384~395 (2012)
  124. Jiang JX, "Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4", NOX1 inhibitor in vivo, 2012, pp.53, 289~296
  125. Staels B, "Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha", delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease, Hepatology, pp.2013, 58[DOI]
  126. Safadi R, "The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease", Clin Gastroenterol Hepatol, 12, pp.2085~2091 (2014)
  127. Gonzalez EO, "The effects of Maraviroc on liver fibrosis in HIV", HCV co-infected patients, 2014, pp.17(4 Suppl 3), 19643~
  128. Yang JJ, "Hedgehog signaling pathway as key player in liver fibrosis: new insights and perspectives", Expert Opin Ther Targets, 18, pp.1011~1021 (2014)
  129. Samarakoon R, "TGF-β signaling in tissue fibrosis: redox controls, target genes and therapeutic opportunities", Cell Signal, 25, pp.264~268 (2013)
  130. Tam J, "Peripheral cannabinoid-1receptor inverse agonism reduces obesity by reversing leptin resistance", Cell Metab, 16, pp.167~179 (2012)
  131. Baghdasaryan A, "Dual farnesoid X receptor", TGR5 agonist INT-767 reduces liver injury in the Mdr2-, -) mouse cholangiopathy model by promoting biliary HCO–3 output, pp.Hepatology, 2011[DOI]
  132. 엄영우, "Mesenchymal stem cell therapy for liver fibrosis", The Korean Journal of Internal Medicine, 30(5), pp.580~589 (2015), 대한내과학회[DOI]

관련 논문AI추천

Anti-fibrotic treatments for chronic liver diseases: The present and the futureHideki Fujii, Masaru Enomoto, Misako Sato-Matsubara, Naoshi Odagiri, Norifumi Kawada, Tsutomu Matsubara대한간학회 · Clinical and Molecular Hepatology2021 · 제27권 제3호A review of liver fibrosis and cirrhosis regressionMichael J. Lee대한병리학회 · Journal of Pathology and Translational Medicine2023 · 제57권 제4호The fibrogenic process and the unleashing of acute-on-chronic liver failureGuillermo Nahúm López-Sánchez, Mayra Dóminguez-Pérez, Misael Uribe, Natalia Nuño-Lámbarri대한간학회 · Clinical and Molecular Hepatology2020 · 제26권 제1호Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension엄영우, Kwang Yong Shim, Moon Young Kim, Seong Hee Kang, Soon Koo Baik대한내과학회 · The Korean Journal of Internal Medicine2018 · 제33권 제3호Recent Advances in the Pathogenesis and Clinical Evaluation of Portal Hypertension in Chronic Liver DiseaseKawada Norifumi, Kotani Kohei거트앤리버 소화기연관학회협의회 · Gut and Liver2024 · 제18권 제1호Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis권상옥, 김문영, 백순구, 장윤옥, 전백규대한간학회 · Clinical and Molecular Hepatology2015 · 제21권 제2호

이 간행물의 다른 논문 (23건)

Diagnosis and treatment of cystic lung disease이은주, 박상훈pp. 229-238Linking resistin, inflammation, and cardiometabolic diseases곽미경, 박형규, Rexford S. Ahima, 김혜정pp. 239-247Targeting the CXCL12/CXCR4 axis in acute myeloid leukemia: from bench to bedside조병식, 김희제, Marina Konoplevapp. 248-257Serum vascular endothelial growth factor as a marker of asthma exacerbation김주희pp. 258-260Ultrasound-guided percutaneous portal transplantation of peripheral blood monocytes in patients with liver cirrhosis유정주, 조유리, 윤정환, 이민종, 김윤준, 유수종, Chung Yong Kim, 이윤빈, 김원, 이동현, 조은주, 이정민, 이정훈pp. 261-268
원문 보기