Molecular mechanisms of hepatobiliary and pancreatic diseases in patients with inflammatory bowel disease
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摘要:
炎症性肠病(IBD)是一种病因与发病机制不明的、慢性非特异性肠道炎症性疾病,常伴随有肠外表现,可涉及包括肝胆胰在内的多个器官累及,对IBD的预后转归有重要的影响。肝胆胰器官并发症主要包括原发性硬化性胆管炎、原发性胆汁性胆管炎、自身免疫性肝炎、IgG4相关性硬化性胆管炎、急性胰腺炎、慢性胰腺炎、自身免疫性胰腺炎、非特异性胰酶升高等。IBD相关肝胆胰并发症的发生是在具有遗传易感性的个体中,环境因素和免疫因素等共同作用下所致,综述了其发病机制的相关研究进展。
Abstract:Inflammatory bowel disease( IBD) is a non-specific chronic intestinal inflammatory disease with unknown etiology and pathogenesis and is often accompanied by extraintestinal manifestations involving multiple organs including the liver,the gallbladder,and the pancreas,with an important impact on the prognosis of IBD. Hepatobiliary and pancreatic complications mainly include primary sclerosing cholangitis,primary biliary cholangitis,autoimmune hepatitis,IgG4-associated sclerosing cholangitis,acute pancreatitis,chronic pancreatitis,autoimmune pancreatitis,and nonspecific increase in pancreatic enzyme. IBD-related hepatobiliary and pancreatic complications are caused by the combination of environmental and immune-mediated factors in individuals with genetic susceptibility,and this article summarizes the current research advances in the pathogenesis of such hepatobiliary inflammatory bowel disease; liver diseases; biliary tract diseases;pancreatic diseases; and pancreatic complications.
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Key words:
- inflammatory bowel disease /
- liver diseases /
- biliary tract disease /
- pacreatic diseases
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[1]NG SC,SHI HY,HAMIDI N,et al.Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century:A systematic review of population-based studyies[J].Lancet,2018,390(10114):2769-2778. [2]ANIWAN S,PARK SH,LOFTUS EV Jr.Epidemiology,natural history,and risk stratification of Crohn's disease[J].Gastroenterol Clin North Am,2017,46(3):464-480. [3]BOUMA G,STROBER W.The immunological and genetic basis of inflammatory bowel disease[J].Nat Rev Immunol,2003,7(3):521-533. [4]CHAPMAN MH,THORBURN D,HIRSCHFIELD GM,et al.British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis[J].Gut,2019,68(8):1356-1378. [5]RUST C,BRAND S.PSC:Protect and serve with colitis:Does it help the liver to have severe ulcerative colitis?[J].Gut,2011,60(9):1165-1166. [6]CHAPMAN RW,ARBORGH BA,RHODES JM,et al.Primary sclerosing cholangitis:A review of its clinical features,cholangiography,and hepatic histology[J].Gut,1980,21(10):870-877. [7]OLIVEIRA LC,PORTA G,MARIN ML,et al.Autoimmune hepatitis,HLA and extended haplotypes[J].Autoimmun Rev,2011,10(4):189-193. [8]LIU JZ,HOV JR,FOLSERAAS T,et al.Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis[J].Nat Genet,2013,45(6):670-675. [9]CARIO E,BROWN D,MCKEE M,et al.Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium[J].Am J Pathol,2002,160(1):165-173. [10]HIRSCHFIELD GM,KARLSEN TH,LINDOR KD,et al.Primary sclerosing cholangitis[J].Lancet,2013,382(9904):1587-1599. [11]DAWSON PA,KARPEN SJ.Intestinal transport and metabolism of bile acids[J].J Lipid Res,2015,56(6):1085-1099. [12]DAWSON PA.Toxic bile and sclerosing cholangitis:Is there a role for pharmacological interruption of the bile acid enterohepatic circulation?[J].Hepatology,2016,63(2):363-364. [13]WILLIAMSON KD,CHAPMAN RW.New therapeutic strategies for primary sclerosing cholangitis[J].Semin Liver Dis,2016,36(1):5-14. [14]TABIBIAN JH,VARGHESE C,LARUSSO NF,et al.The enteric microbiome in hepatobiliary health and disease[J].Liver Int,2016,36(4):480-487. [15]KEVANS D,TYLER AD,HOLM K,et al.Characterization of intestinal microbiota in ulcerative colitis patients with and without primary sclerosing cholangitis[J].J Crohns Colitis,2016,10(3):330-337. [16]SABINO J,VIEIRA-SILVA S,MACHIELS K,et al.Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD[J].Gut,2016,65(10):1681-1689. [17]PATEL M,WATSON A,RUSHBROOK S.A mechanistic insight into the role of gut microbiota in the pathogenesis of primary sclerosing cholangitis[J].Gastroenterology,2019,157(6):1686-1688. [18]LIAO L,SCHNEIDER KM,GALVEZ E,et al.Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis[J].Gut,2019,68(8):1477-1492. [19]BOONSTRA K,de VRIES EM,van GELOVEN N,et al.Risk factors for primary sclerosing cholangitis[J].Liver Int,2016,36(1):84-91. [20]ANDERSEN IM,TENGESDAL G,LIE BA,et al.Effects of coffee consumption,smoking,and hormones on risk for primary sclerosing cholangitis[J].Clin Gastroenterol Hepatol,2014,12(6):1019-1028. [21]GATSELIS NK,ZACHOU K,KOUKOULIS GK,et al.Autoimmune hepatitis,one disease with many faces:Etiopathogenetic,clinico-laboratory and histological characteristics[J].World J Gastroenterol,2015,21(1):60-83. [22]GRNBK L,VILSTRUP H,JEPSEN P.Autoimmune hepatitis in denmark:Incidence,prevalence,prognosis,and causes of death.Anationwide registry-based cohort study[J].J Hepatol,2014,60(3):612-617. [23]PENG M,LI Y,ZHANG M,et al.Clinical features in different age groups of patients with autoimmune hepatitis[J].Exp Ther Med,2014,7(1):145-148. [24]de BOER YS,van GERVEN NM,ZWIERS A,et al.Genome-wide association study identifies variants associated with autoimmune hepatitis type 1[J].Gastroenterology,2014,147(2):443-452.e5. [25]van GERVEN NM,de BOER YS,ZWIERS A,et al.HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1[J].Genes Immun,2015,16(4):247-252. [26]BITTENCOURT PL,GOLDBERG AC,CANADO EL,et al.Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2[J].Am J Gastroenterol,1999,94(7):1906-1913. [27]CZAJA AJ,CARPENTER HA,MOORE SB.HLA DRB1*13 as a risk factor for type 1 autoimmune hepatitis in North American patients[J].Dig Dis Sci,2008,53(2):522-528. [28]FERRI S,LONGHI MS,DE MOLO C,et al.A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis[J].Hepatology,2010,52(3):999-1007. [29]LONGHI MS,MEDA F,WANG P,et al.Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis[J].Hepatology,2008,47(2):581-591. [30]LIANG M,LIWEN Z,YUN Z,et al.The Imbalance between FOXP3+TREGS and Th1/Th17/Th22 Cells in patients with newly diagnosed autoimmune hepatitis[J].J Immunol Res,2018,2018:3753081. [31]LIU Y,YAN W,YUAN W,et al.Treg/Th17 imbalance is associated with poor autoimmune hepatitis prognosis[J].Clin Immunol,2019,198:79-88. [32]OO YH,WESTON CJ,LALOR PF,et al.Distinct roles for CCR4and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver[J].J Immunol,2010,184(6):2886-2898. [33]ZHANG X,XIAO X,LAN P,et al.OX40 co-stimulation inhibits Foxp3 expression and treg induction via BATF3-dependent and independent mechanisms[J].Cell Rep,2018,24(3):607-618. [34]LEI W,ZENG DX,ZHU CH,et al.The upregulated expression of OX40/OX40L and their promotion of T cells proliferation in the murine model of asthma[J].J Thorac Dis,2014,6(7):979-987. [35]STURGEON C,FASANO A.Zonulin,a regulator of epithelial and endothelial barrier functions,and its involvement in chronic inflammatory diseases[J].Tissue Barriers,2016,4(4):e1251384. [36]CANFORA EE,JOCKEN JW,BLAAK EE.Short-chain fatty acids in control of body weight and insulin sensitivity[J].Nat Rev Endocrinol,2015,11(10):577-591. [37]DEN BESTEN G,van EUNEN K,GROEN AK,et al.The role of short-chain fatty acids in the interplay between diet,gut microbiota,and host energy metabolism[J].J Lipid Res,2013,54(9):2325-2340. [38]SHENG L,JENA PK,HU Y,et al.Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation[J].J Pathol,2017,243(4):431-441. [39]FLOREANI A,RESTREPO-JIMNEZ P,SECCHI MF,et al.Etiopathogenesis of autoimmune hepatitis[J].J Autoimmun,2018,95:133-143. [40]MA WT,CHEN DK.Immunological abnormalities in patients with primary biliary cholangitis[J].Clin Sci(Lond),2019,133(6):741-760. [41]JOSHITA S,UMEMURA T,TANAKA E,et al.Genetics and epigenetics in the pathogenesis of primary biliary cholangitis[J].Clin JGastroenterol,2018,11(1):11-18. [42]TANAKA A,LEUNG P,GERSHWIN ME.The genetics of primary biliary cholangitis[J].Curr Opin Gastroenterol,2019,35(2):93-98. [43]DARLAY R,AYERS KL,MELLS GF,et al.Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis[J].PLo S Genet,2018,14(12):e1007833. [44] QIU F,TANG R,ZUO X,et al.A genome-wide association study identifies six novel risk loci for primary biliary cholangitis[J].Nat Commun,2017,8:14828. [45]LAZARIDIS KN,TALWALKAR JA.Clinical epidemiology of primary biliary cirrhosis:Incidence,prevalence,and impact of therapy[J].JClin Gastroenterol,2007,41(5):494-500. [46]YANG GX,LIAN ZX,CHUANG YH,et al.Adoptive transfer of CD8(+)T cells from transforming growth factor beta receptor type II(dominant negative form)induces autoimmune cholangitis in mice[J].Hepatology,2008,47(6):1974-1982. [47]BERNUZZI F,FENOGLIO D,BATTAGLIA F,et al.Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis[J].J Autoimmun,2010,35(3):176-180. [48]LAN RY,CHENG C,LIAN ZX,et al.Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis[J].Hepatology,2006,43(4):729-737. [49]LIASKOU E,PATEL SR,WEBB G,et al.Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-γsecreting cells[J].J Autoimmun,2018,94:143-155. [50]DAVIES YK,COX KM,ABDULLAH BA,et al.Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin:An immunomodulating antibiotic[J].J Pediatr Gastroenterol Nutr,2008,47(1):61-67. [51]YANG CY,MA X,TSUNEYAMA K,et al.IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis:Implications for therapy[J].Hepatology,2014,59(5):1944-1953. [52]SONG Y,YANG H,JIANG K,et al.miR-181a regulates Th17 cells distribution via up-regulated BCL-2 in primary biliary cholangitis[J].Int Immunopharmacol,2018,64:386-393. [53]YAO Y.Roles of henatopoietic system,cytokines and intestinal bacteria in the pathogeny of murine primary biliary cirrhosis[D].Hefei:U-niversity of Science and Technology of China,2015.(in Chinese)姚远.原发性胆汁性肝硬化模型鼠发病过程中造血系统、细胞因子、肠道菌群的作用探究[D].合肥:中国科学技术大学,2015. [54]LV LX,FANG DQ,SHI D,et al.Alterations and correlations of the gut microbiome,metabolism and immunity in patients with primary biliary cirrhosis[J].Environ Microbiol,2016,18(7):2272-2286. [55]HIRAMATSU K,HARADA K,TSUNEYAMA K,et al.Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene in gallbladder bile from patients with primary biliary cirrhosis[J].JHepatol,2000,33(1):9-18. [56]OTA M,KATSUYAMA Y,HAMANO H,et al.Two critical genes(HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis[J].Immunogenetics,2007,59(1):45-52. [57]PARK DH,KIM MH,OH HB,et al.Substitution of aspartic acid at position 57 of the DQbeta1 affects relapse of autoimmune pancreatitis[J].Gastroenterology,2008,134(2):440-446. [58]WATANABE T,YAMASHITA K,FUJIKAWA S,et al.Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced Ig G4 responses in autoimmune pancreatitis[J].Arthritis Rheum,2012,64(3):914-924. [59]MAEHARA T,MORIYAMA M,NAKASHIMA H,et al.Interleukin-21 contributes to germinal centre formation and immunoglobulin G4production in Ig G4-related dacryoadenitis and sialoadenitis,socalled Mikulicz's disease[J].Ann Rheum Dis,2012,71(12):2011-2019. [60]LIAN M,WANG Q,JIANG X,et al.The immunobiology of receptor activator for nuclear factor kappa B ligand and myeloid-derived suppressor cell activation in immunoglobulin G4-related sclerosing cholangitis[J].Hepatology,2018,68(5):1922-1936. [61]HARADA K,HSU M,IKEDA H,et al.Application and validation of a new histologic staging and grading system for primary biliary cirrhosis[J].J Clin Gastroenterol,2013,47(2):174-181. [62]SINGAL AK,STANCA CM,CLARK V,et al.Natural history of small duct primary sclerosing cholangitis:A case series with review of the literature[J].Hepatol Int,2011,5(3):808-813. [63]ZHANG S,LUO J,LI J,et al.Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease:2-year clinical experience[J].Clin Chem Lab Med,2017,55(6):865-875. [64]CHEN YT,SU JS,TSENG CW,et al.Inflammatory bowel disease on the risk of acute pancreatitis:A population-based cohort study[J].J Gastroenterol Hepatol,2016,31(4):782-787. [65]PEZZILLI R,PAGANO N.Benign exocrine pancreatic diseases in inflammatory bowel diseases[J].Dig Dis,2017,35(5):449-453. [66]TSEN A,ALISHAHI Y,ROSENKRANZ L.Autoimmune pancreatitis and inflammatory bowel disease:An updated review[J].J Clin Gastroenterol,2017,51(3):208-214. [67]KU Y,HONG SM,FUJIKURA K,et al.IL-8 expression in granulocytic epithelial lesions of idiopathic duct-centric pancreatitis(type2 autoimmune pancreatitis)[J].Am J Surg Pathol,2017,41(8):1129-1138.
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