Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection

References

• Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet (London, England). 2015;386(10003):1546–1555.
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.
   PubMed Web of Science ®Google Scholar
• Ott JJ, Horn J, Krause G, et al. Time trends of chronic HBV infection over prior decades NDAS a global analysis. J Hepatol. 2017;66(1):48–54.
   PubMed Web of Science ®Google Scholar
• Ott JJ, Stevens GA, Groeger J, et al. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212–2219.
   PubMed Web of Science ®Google Scholar
• Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):686–690.
   PubMed Web of Science ®Google Scholar
• Lin CW, Huang XL, Liu HL, et al. Interactions of hepatitis B virus infection with nonalcoholic fatty liver disease: possible mechanisms and clinical impact. Dig Dis Sci. 2015;60(12):3513–3524.
   PubMed Web of Science ®Google Scholar
• Wang MM, Wang GS, Shen F, et al. Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors. Dig Dis Sci. 2014;59(10):2571–2579.
   PubMed Web of Science ®Google Scholar
• Machado MV, Oliveira AG, Cortez-Pinto H. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients. J Gastroenterol Hepatol. 2011;26:1361–1367.
   PubMed Web of Science ®Google Scholar
• Chu CM, Lin DY, Liaw YF. Clinical and virological characteristics post HBsAg seroclearance in hepatitis B virus carriers with hepatic steatosis versus those without. Dig Dis Sci. 2013;58(1):275–281.
   PubMed Web of Science ®Google Scholar
• Chen YC, Sheen IS, Chu CM, et al. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology. 2002;123(4):1084–1089.
   PubMed Web of Science ®Google Scholar
• Calzadilla Bertot L, Adams LA. The natural course of non-alcoholic fatty liver disease. IJMS. 2016;17(5):774.
   Web of Science ®Google Scholar
• Gao C, Fang L, Zhao HC, et al. Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma: a cross-sectional case-control study from Chinese patients with HBV infection. Hepatobiliary Pancreatic Dis Int. 2013;12(4):385–393.
   PubMed Web of Science ®Google Scholar
• Huang YW, Wang TC, Lin SC, et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis B patients with newly diagnosed diabetes: a nationwide cohort study. Clin Infect Dis. 2013;57(12):1695–1702.
   PubMed Web of Science ®Google Scholar
• Goh S-C, Ho EL-M, Goh K-L. Prevalence and risk factors of non-alcoholic fatty liver disease in a multiracial suburban Asian population in Malaysia. Hepatol Int. 2013;7(2):548–554.
   PubMed Web of Science ®Google Scholar
• Chan WK, Tan AT, Vethakkan SR, et al. Non-alcoholic fatty liver disease in diabetics-Prevalence and predictive factors in a multiracial hospital clinic population in Malaysia. J Gastroenterol Hepatol. 2013;28(8):1375–1383.
   PubMed Web of Science ®Google Scholar
• Yong YK, Tan HY, Saeidi A, et al. Decrease of CD69 levels on TCR Vα7.2 + CD4 + innate-like lymphocytes is associated with impaired cytotoxic functions in chronic hepatitis B virus-infected patients. Innate Immun. 2017;23(5):459–467. doi:10.1177/1753425917714854.
   PubMed Web of Science ®Google Scholar
• World Health Organization Western Pacific Region IAftSoO, International Obesity Task Force. Redefining obesity and its treatment. Geneva (Switzerland): WHO; 2000.
   Google Scholar
• Li Y, Huang YS, Wang ZZ, et al. Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B. Aliment Pharmacol Ther. 2016;43(4):458–469.
   PubMed Web of Science ®Google Scholar
• McDonald JH. Handbook of biological statistics. 3rd ed. Baltimore (MD): Sparky House Publishing; 2014.
   Google Scholar
• Angulo P. Diagnosing steatohepatitis and predicting liver-related mortality in patients with NAFLD: two distinct concepts. Hepatology. 2011;53(6):1792–1794.
   PubMed Web of Science ®Google Scholar
• Shi JP, Fan JG, Wu R, et al. Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection. J Gastroenterol Hepatol. 2008;23(9):1419–1425.
   PubMed Web of Science ®Google Scholar
• Chan AWH, Wong GLH, Chan H-Y, et al. Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B. J Gastroenterol Hepatol. 2017;32(3):667–676.
   PubMed Web of Science ®Google Scholar
• Wong GL, Wong VW, Choi PC, et al. Clinical factors associated with liver stiffness in hepatitis B e antigen-positive chronic hepatitis B patients. Clin Gastroenterol Hepatol. 2009;7(2):227–233.
   PubMed Web of Science ®Google Scholar
• Croagh CM, Bell SJ, Slavin J, et al. Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B. Liver Int. 2010;30(8):1115–1122.
   PubMed Web of Science ®Google Scholar
• Praneenararat S, Chamroonkul N, Sripongpun P, et al. HBV DNA level could predict significant liver fibrosis in HBeAg negative chronic hepatitis B patients with biopsy indication. BMC Gastroenterol. 2014;14:218.
   PubMed Web of Science ®Google Scholar
• Cho Y, Tokuhara D, Morikawa H, et al. Transient elastography-based liver profiles in a hospital-based pediatric population in Japan. PLoS One. 2015;10(9):e0137239.
   PubMed Web of Science ®Google Scholar
• Seto WK, Hui RWH, Mak LY, et al. Association between hepatic steatosis, measured by controlled attenuation parameter, and fibrosis burden in chronic hepatitis B. Clin Gastroenterol Hepatol. 2018;16(4):575–583.
   PubMed Web of Science ®Google Scholar
• Kim SU, Lee JH, Kim DY, et al. Prediction of liver-related events using fibroscan in chronic hepatitis B patients showing advanced liver fibrosis. PLoS One. 2012;7(5):e36676.
   PubMed Web of Science ®Google Scholar
• Wong GL, Chan HL, Yu Z, et al. Liver fibrosis progression is uncommon in patients with inactive chronic hepatitis B: a prospective cohort study with paired transient elastography examination. J Gastroenterol Hepatol. 2013;28(12):1842–1848.
   PubMed Web of Science ®Google Scholar
• Harkisoen S, Arends JE, van den Hoek JA, et al. Historic and current hepatitis B viral DNA and quantitative HBsAg level are not associated with cirrhosis in non-Asian women with chronic hepatitis B. Int J Infect Dis. 2014;29:133–138.
   PubMed Web of Science ®Google Scholar
• Ceylan B, Arslan F, Batirel A, et al. Impact of fatty liver on hepatitis B virus replication and virologic response to tenofovir and entecavir. Turk J Gastroenterol. 2016;27(1):42–46.
   PubMed Web of Science ®Google Scholar
• Hui RWH, Seto WK, Cheung KS, et al. Inverse relationship between hepatic steatosis and hepatitis B viremia: results of a large case-control study. J Viral Hepat. 2018;25(1):97–104.
   PubMed Web of Science ®Google Scholar
• Goyal SK, Jain AK, Dixit VK, et al. HBsAg level as predictor of liver fibrosis in HBeAg positive patients with chronic hepatitis B virus infection. J Clin Exp Hepatol. 2015;5(3):213–220.
   PubMed Web of Science ®Google Scholar
• Hadziyannis SJ, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2001;34(4):617–624.
   PubMed Web of Science ®Google Scholar
• McMahon BJ. Natural history of chronic hepatitis B - clinical implications. Medscape J Med. 2008;10(4):91.
   PubMedGoogle Scholar
• Yu M-W, Shih W-L, Lin C-L, et al. Body-mass index and progression of hepatitis B: a population-based cohort study in men. J Clin Oncol. 2008;26(34):5576–5582.
   PubMed Web of Science ®Google Scholar
• Wong GL-H, Wong VW-S, Choi PC-L, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58(1):111–117.
   PubMed Web of Science ®Google Scholar
• de Vries JE. The role of IL-13 and its receptor in allergy and inflammatory responses. J Allergy Clin Immunol. 1998;102(2):165–169.
   PubMed Web of Science ®Google Scholar
• Izuhara K, Arima K. Signal transduction of IL-13 and its role in the pathogenesis of bronchial asthma. Drug News Perspect. 2004;17(2):91–98.
   PubMedGoogle Scholar
• Wills-Karp M, Chiaramonte M. Interleukin-13 in asthma. Curr Opin Pulm Med. 2003;9(1):21–27.
   PubMed Web of Science ®Google Scholar
• Wills-Karp M, Luyimbazi J, Xu X, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282(5397):2258–2261.
   PubMed Web of Science ®Google Scholar
• Grunig G, Warnock M, Wakil AE, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282(5397):2261–2263.
   PubMed Web of Science ®Google Scholar
• Doran E, Cai F, Holweg CTJ, et al. Interleukin-13 in asthma and other eosinophilic disorders. Front Med (Lausanne)). 2017;4:139.
   PubMed Web of Science ®Google Scholar
• Tokayer A, Carsons SE, Chokshi B, et al. High levels of interleukin 13 in rheumatoid arthritis sera are modulated by tumor necrosis factor antagonist therapy: association with dendritic cell growth activity. J Rheumatol. 2002;29(3):454–461.
   PubMed Web of Science ®Google Scholar
• Chiaramonte MG, Donaldson DD, Cheever AW, et al. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest. 1999;104(6):777–785.
   PubMed Web of Science ®Google Scholar
• Lee CG, Homer RJ, Zhu Z, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med. 2001;194(6):809–821.
   PubMed Web of Science ®Google Scholar
• Chiaramonte MG, Schopf LR, Neben TY, et al. IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs. J Immunol. 1999;162(2):920–930.
   PubMed Web of Science ®Google Scholar
• Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779–788.
   PubMed Web of Science ®Google Scholar
• Hancock A, Armstrong L, Gama R, et al. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol. 1998;18(1):60–65.
   PubMed Web of Science ®Google Scholar
• Shimamura T, Fujisawa T, Husain SR, et al. Novel role of IL-13 in fibrosis induced by nonalcoholic steatohepatitis and its amelioration by IL-13R-directed cytotoxin in a rat model. J Immunol. 2008;181(7):4656–4665.
   PubMed Web of Science ®Google Scholar
• Borthwick LA, Wynn TA, Fisher AJ. Cytokine mediated tissue fibrosis. Biochim Biophys Acta. 2013;1832(7):1049–1060.
   PubMed Web of Science ®Google Scholar
• Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-β: the master regulator of fibrosis. Nat Rev Nephrol. 2016;12(6):325–338.
   PubMed Web of Science ®Google Scholar
• Kelly-Welch AE, Hanson EM, Boothby MR, et al. Interleukin-4 and interleukin-13 signaling connections maps. Science. 2003;300(5625):1527–1528.
   PubMed Web of Science ®Google Scholar
• Hirst SJ, Hallsworth MP, Peng Q, et al. Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain. Am J Respir Crit Care Med. 2002;165(8):1161–1171.
   PubMed Web of Science ®Google Scholar
• Pope SM, Brandt EB, Mishra A, et al. IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism. J Allergy Clin Immunol. 2001;108(4):594–601.
   PubMed Web of Science ®Google Scholar
• Kawakami K, Taguchi J, Murata T, et al. The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway. Blood. 2001;97(9):2673–2679.
   PubMed Web of Science ®Google Scholar
• Tarantino G, Cabibi D, Camma C, et al. Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C. J Viral Hepat. 2008;15(7):523–530.
   PubMed Web of Science ®Google Scholar
• Proctor WR, Chakraborty M, Chea LS, et al. Eosinophils mediate the pathogenesis of halothane-induced liver injury in mice. Hepatology. 2013;57(5):2026–2036.
   PubMed Web of Science ®Google Scholar
• Machado MV, Yang Y, Diehl AM. The benefits of restraint: a pivotal role for IL-13 in hepatic glucose homeostasis. J Clin Invest. 2013;123(1):115–117.
   PubMed Web of Science ®Google Scholar
• Darkhal P, Gao M, Ma Y, et al. Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice. Int J Obes (Lond)). 2015;39(8):1292–1299.
   PubMed Web of Science ®Google Scholar
• Gieseck RL, Ramalingam TR, Hart KM, et al. Interleukin-13 activates distinct cellular pathways leading to ductular reaction, steatosis, and fibrosis. Immunity. 2016;45(1):145–158.
   PubMed Web of Science ®Google Scholar
• Stanya KJ, Jacobi D, Liu S, et al. Direct control of hepatic glucose production by interleukin-13 in mice. J Clin Invest. 2013;123(1):261–271.
   PubMed Web of Science ®Google Scholar
• Guha M, Bai W, Nadler JL, et al. Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem. 2000;275(23):17728–17739.
   PubMed Web of Science ®Google Scholar
• Shanmugam N, Reddy MA, Guha M, et al. High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes. 2003;52(5):1256–1264.
   PubMed Web of Science ®Google Scholar
• Matsukura S, Stellato C, Georas SN, et al. Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. Am J Respir Cell Mol Biol. 2001;24(6):755–761.
   PubMed Web of Science ®Google Scholar
• Pope SM, Fulkerson PC, Blanchard C, et al. Identification of a cooperative mechanism involving interleukin-13 and eotaxin-2 in experimental allergic lung inflammation. J Biol Chem. 2005;280(14):13952–13961.
   PubMed Web of Science ®Google Scholar
• Tacke F, Trautwein C, Yagmur E, et al. Up-regulated eotaxin plasma levels in chronic liver disease patients indicate hepatic inflammation, advanced fibrosis and adverse clinical course. J Gastroenterol Hepatol. 2007;22(8):1256–1264.
   PubMed Web of Science ®Google Scholar
• Song YS, Joo HW, Park IH, et al. Granulocyte-colony stimulating factor prevents the development of hepatic steatosis in rats. Ann Hepatol. 2015;14(2):243–250.
   PubMed Web of Science ®Google Scholar
• Song YS, Fang CH, So BI, et al. Therapeutic effects of granulocyte-colony stimulating factor on non-alcoholic hepatic steatosis in the rat. Ann Hepatol. 2013;12(1):115–122.
   PubMed Web of Science ®Google Scholar
• Jin SZ, Meng XW, Sun X, et al. Granulocyte colony-stimulating factor enhances bone marrow mononuclear cell homing to the liver in a mouse model of acute hepatic injury. Dig Dis Sci. 2010;55(10):2805–2813.
   PubMed Web of Science ®Google Scholar
• Gaia S, Smedile A, Omede P, et al. Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol. 2006;45(1):13–19.
   PubMed Web of Science ®Google Scholar
• Girija A, Shankar EM, Larsson M. Could SARS-CoV-2-induced hyperinflammation magnify the severity of coronavirus disease (CoViD-19) leading to acute respiratory distress syndrome?. Front Immunol. 2020;11:1206.
   PubMed Web of Science ®Google Scholar
• Ji Y, Dahmen U, Madrahimov N, et al. G-CSF administration in a small-for-size liver model. J Invest Surg. 2009;22(3):167–177.
   PubMed Web of Science ®Google Scholar
• Schmidt-Arras D, Rose-John S. IL-6 pathway in the liver: from physiopathology to therapy. J Hepatol. 2016;64(6):1403–1415.
   PubMed Web of Science ®Google Scholar
• Blindenbacher A, Wang X, Langer I, et al. Interleukin 6 is important for survival after partial hepatectomy in mice. Hepatology. 2003;38(3):674–682.
   PubMed Web of Science ®Google Scholar
• Wuestefeld T, Klein C, Streetz KL, et al. Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration. J Biol Chem. 2003;278(13):11281–11288.
   PubMed Web of Science ®Google Scholar
• Weng SY, Wang X, Vijayan S, et al. IL-4 receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversal. EBioMedicine. 2018;29:92–103.
   PubMed Web of Science ®Google Scholar
• Niu H, Li Y, Li H, et al. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity. Sci Rep. 2016;6:20171.
   PubMed Web of Science ®Google Scholar
• Kovalovich K, DeAngelis RA, Li W, et al. Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice. Hepatology. 2000;31(1):149–159.
   PubMed Web of Science ®Google Scholar
• Sun R, Tian Z, Kulkarni S, et al. IL-6 prevents T cell-mediated hepatitis via inhibition of NKT cells in CD4+ T cell- and STAT3-dependent manners. J Immunol. 2004;172(9):5648–5655.
   PubMed Web of Science ®Google Scholar
• Rio A, Gassull MA, Aldeguer X, et al. Reduced liver injury in the interleukin-6 knockout mice by chronic carbon tetrachloride administration. Eur J Clin Invest. 2008;38(5):306–316.
   PubMed Web of Science ®Google Scholar
• Jin X, Zimmers TA, Perez EA, et al. Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. Hepatology. 2006;43(3):474–484.
   PubMed Web of Science ®Google Scholar
• Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of [corrected] kupffer cells on stellate cells. Hepatology. 2006;44(6):1487–1501.
   PubMed Web of Science ®Google Scholar
• Dogru T, Ercin CN, Erdem G, et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103(12):3217–3218.
   PubMed Web of Science ®Google Scholar
• Wieckowska A, Papouchado BG, Li Z, et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterology. 2008;103(6):1372–1379.
   PubMed Web of Science ®Google Scholar
• Kao J-T, Lai H-C, Tsai S-M, et al. Rather than interleukin-27, interleukin-6 expresses positive correlation with liver severity in naïve hepatitis B infection patients. Liver Int. 2012;32(6):928–936.
   PubMed Web of Science ®Google Scholar
• Shah S, Ma Y, Scherzer R, et al. Association of HIV, hepatitis C virus and liver fibrosis severity with interleukin-6 and C-reactive protein levels. AIDS. 2015;29(11):1325–1333.
   PubMed Web of Science ®Google Scholar
• Kong X, Horiguchi N, Mori M, et al. Cytokines and STATs in liver fibrosis. Front Physiol. 2012;3:(69).
   PubMed Web of Science ®Google Scholar
• Xiang D-M, Sun W, Ning B-F, et al. The HLF/IL-6/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis. Gut. 2018;67(9):1704–1715.
   PubMed Web of Science ®Google Scholar