Research advances in the pathogenesis of nonalcoholic fatty liver disease-related hepatocellular carcinoma
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摘要: 非酒精性脂肪性肝病相关肝细胞癌(NAFLD-HCC)的发病率逐渐上升。其发病机制与遗传和表观遗传修饰、代谢、免疫、肠道微生态、内分泌通路和昼夜节律的改变有关。总结了目前NAFLD-HCC发病机制的现有数据,认为多因素共同交互作用可引起HCC的发生。Abstract: The incidence rate of nonalcoholic fatty liver disease-related hepatocellular carcinoma ( NAFLD-HCC) is gradually increasing.Its pathogenesis is associated with the changes in genetic and epigenetic modifications, metabolism, immunity, intestinal microecology, endocrine pathways, and circadian rhythm. This article summarizes the available data on the pathogenesis of NAFLD-HCC and points out that HCC is caused by the interactions between multiple factors.
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Key words:
- non-alcoholic fatty liver disease /
- liver neoplasms /
- pathologic processes
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[1]National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association.Guidelines of prevention and treatment for nonalcoholic fatty liver disease:A 2018 update[J].J Clin Hepatol, 2018, 34 (5) :947-957. (in Chinese) 中华医学会肝病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病防治指南 (2018年更新版) [J].临床肝胆病杂志, 2018, 34 (5) :947-957. [2]YOUNOSSI Z, OTGONSUREN M, Henry L, et al.Association of non-alcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004-2009[J].Hepatology, 2015, 62 (6) :1723-1730. [3]ASCHA M, HANOUNEH I, LOPZ R, et al.The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis[J].Hepatology, 2010, 51 (6) :1972-1978. [4]de MINICIS S, AGOSTINELLI L, RYCHLICKI C, et al.HCCdevelopment is associated to peripheral insulin resistance in a mouse model of NASH[J].PLo S One, 2014, 9 (5) :e97136. [5]SUNNY N, PARKS E, BROWNING J, et al.Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease[J].Cell Metabolism, 2011, 14 (6) :804-810. [6]SUTTI S, JINDAL A, LOCATELLI I, et al.Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH[J].Hepatology, 2014, 59 (3) :886-897. [7]YUAN RS, LI H, SUN JH, et al.Lipid-lowering effect and antioxidant activity of polysaccharide from Schisandra Chinensis in rats with non-alcoholic fatty liver disease induced by high-fat diet[J].J Jilin Univ:Med Edit, 2017, 43 (6) :1103-1108. (in Chinese) 苑荣爽, 李贺, 孙靖辉, 等.北五味子多糖对高脂诱导非酒精性脂肪性肝病大鼠的降血脂作用及其抗氧化活性[J].吉林大学学报:医学版, 2017, 43 (6) :1103-1108. [8]GANDHI C, CHAILLET J, NALESNIK M, et al.Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice[J].Gastroenterology, 2015, 148 (2) :379-391.e4. [9]FENG SH, CHENG J.Pathogenesis of NAFLD associated hepatocellular carcinoma[J/CD].Chin J Liver Dis:Electr Version, 2017, 9 (3) :8-12. (in Chinese) 冯胜虎, 成军.NAFLD相关肝细胞癌的发病机制[J/CD].中国肝脏病杂志:电子版, 2017, 9 (3) :8-12. [10]PORTEIRO B, FONDEVILA MF, DELGADO TC, et al.Hepatic p63 regulates steatosis via IKKβ/ER stress[J].Nat Commun, 2017, 8:15111. [11] LIU XL, CAO HX, WANG BC, et al.miR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1[J].World J Gastroenterol, 2017, 23 (46) :8140-8151. [12]WANG XT, HAN T.A review of relationship between gut microecology and liver disease[J].J Clin Hepatol, 2015, 31 (4) :642-645. (in Chinese) 王晓彤, 韩涛.肠道微生态与肝病的关系[J].临床肝胆病杂志, 2015, 31 (4) :642-645. [13]MA RJ, WU J, ZHOU YN.Relationship between intestinal microflora imbalance and nonalcoholic fatty liver disease[J].JClin Hepatol, 2015, 31 (1) :127-129. (in Chinese) 麻瑞娟, 吴静, 周永宁.肠道微生态失衡与非酒精性脂肪性肝病的关系[J].临床肝胆病杂志, 2015, 31 (1) :127-129. [14]CORBIN K, ZEISEL S.Choline metabolism provides novel insights into non-alcoholic fatty liver disease and its progression[J].Curr Opin Gastroenterol, 2012, 28 (2) :159-165. [15]RIDLON J, HARRIS S, BHOWMIK S, et al.Consequences of bile salt biotransformations by intestinal bacteria[J].Gut Microbes, 2016, 7 (1) :22-39. [16]URDANETA V, CASADESUS J.Interactions between bacteria and bile salts in the gastrointestinal and hepatobiliary tracts[J].Front Med, 2017, 4:163. [17]PONZIANI FR, BHOORI S, CASTELLI C, et al.Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in non alcoholic fatty liver disease[J].Hepatology, 2019, 69 (1) :107-120. [18]GRAT M, WRONKA K, KRASNODEBSKI M, et al.Profile of gut microbiota associated with the presence of hepatocellular cancer in patients with liver cirrhosis[J].Transplant Proc, 2016, 48 (5) :1687-1691. [19]SCHUSTER S, CABRERA D, ARRESE M, et al.Triggering and resolution of inflammation in NASH[J].Nat Rev Gastroenterol Hepatol, 2018, 5 (6) :349-364. [20]ZHANG Y, ZHANG XJ, WANG PX, et al.Reprogramming innate immune signaling in cardiometabolic disease[J].Hypertension, 2017, 69 (5) :747-760. [21]CAI JJ, ZHANG XJ, LI HL.Progress and challenges in the prevention and control of nonalcoholic fatty liver disease[J].Med Res Rev, 2019, 39 (1) :328-348. [22]NAKAGAWA H, UMEMURA A, TANIGUCHI K, et al.ERstress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC Development[J].Cancer Cell, 2014, 26 (3) :331-343. [23]KANG TW, YEVSA T, WOLLER N, et al.Senescence surveillance of pre-malignant hepatocytes limits liver cancer development[J].Nature, 2015, 4 (7374) :547-551. [24]MA C, ZHANG Q, GRETEN T.Non-alcoholic fatty liver disease promotes hepatocellular carcinoma through direct and indirect effects on hepatocytes[J].FEBS J, 2018, 285 (4) :752-762. [25]SCHNEIDER C, TEUFEL A, YEVSA T, et al.Adaptive immunity suppresses formation and progression of diethylnitrosamine-induced liver cancer[J].Gut, 2012, 61 (12) :1733-1743. [26]MA C, KESARWALA A, EGGERT T, et al.NAFLD causes selective CD4+T lymphocyte loss and promotes hepatocarcinogenesis[J].Nature, 2016, 531 (7593) :253-257. [27]TRAN E, TURCOTTE S, GROS A, et al.Cancer immunotherapy based on mutation-specific CD4+T cells in a patient with epithelial cancer[J].Science, 2014, 344 (6184) :641-645. [28]GOMES A, TEIJEIRO A, BUREN S, et al.Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma[J].Cancer Cell, 2016, 30 (1) :161-175. [29]RIVERA C, LATAUSHA G, MONIQUE A, et al.Toll-like receptor-2 deficiency enhances non-alcoholic steatohepatitis[J].BMC Gastroenterol, 2010, 10 (1) :52. [30]ETIENNE L, VIJAY M, GEWIRTZ A, et al.Hepatocyte Tolllike receptor 5 promotes bacterial clearance and protects mice against high-fat diet-induced liver disease[J].Cell Mol Gastroenterol Hepatol, 2016, 2 (5) :584-604. [31]LI ZR, YU RL, YIN WZ, et al.m TOR signaling in X/A-like cells contributes to lipid homeostasis in mice[J].Hepatology, 2019, 69 (2) :860-875. [32]VANDANMAGSAR B, YOUM Y, RAVUSSIN A, et al.The NALP3/NLRP3 Inflammasome Instigates Obesity-Induced Autoinflammation and Insulin Resistance[J].Nat Med, 2011, 17 (2) :179-188. [33]MASAYOSHI T, JUN-ICHI T, AKIKO S, et al.Toxic AGE (TAGE) theory for the pathophysiology of the onset/progression of NAFLD and ALD[J].Nutrients, 2017, 9 (6) :e634. [34]BROUWERS MC, van GREEVENBROEK MM, CANTOR RM, et al.Heritability of nonalcoholic fatty liver disease[J].Gastroenterology, 2009, 137 (4) :1536-1536. [35]LIU YL, PATMAN G, LEATHART J, et al.Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma[J].J Hepatol, 2014, 61 (1) :75-81. [36]TAKAKI Y, SAITO Y, TAKASUGI A, et al.Silencing of microR-NA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis[J].Cancer Sci, 2015, 105 (10) :1254-1260. [37]MANCINA R, DONGIOVANNI P, PETTA S, et al.The MBOAT7-TMC4 Variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of european descent[J].Gastroenterology, 2016, 150 (5) :1219-1230.e6. [38]THABET K, CHAN H, PETTA S, et al.The MBOAT7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B[J].Hepatology, 2017, 65 (6) :1840-1850. [39]SPELIOTES E, YERGESARMSTRONG L, WU J, et al.Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits 148[J].PLo S Genetics, 2011, 7 (3) :e1001324. [40]PETTA S, MIELE L, BUGIANESI E, et al.Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease[J].PLo S One, 2014, 9 (2) :e87523. [41]VALENI L, MOTTA B, ALISI A, et al.LPIN1 rs13412852 polymorphism in pediatric nonalcoholic fatty liver disease[J].JPediatr Gastroenterol Nutr, 2012, 54 (5) :588-593. [42]IACLBAZZI V, CASTEGNA A, INFANTINO V, et al.Mitochondrial DNA methylation as a next-generation biomarker and diagnostic tool[J].Mol Genet Metab, 2013, 110 (1-2) :25-34. [43]ESLAM M, VALENTI L, ROMEO S.Genetics and epigenetics of NAFLD and NASH:Clinical impact[J].J Hepatol, 2018, 68 (2) :268-279. [44]LIY XL, CAO HX, WANG BC, et al.miR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1[J].World J Gastroenterol, 2017, 23 (46) :8140-8151. [45]ALISI A, MASOTTI A, NOBILI V.Profiling microRNA expression:a snapshot of nonalcoholic steatohepatitis and a recording of its pathogenesis[J].Hepatology, 2010, 49 (2) :706-707. [46]MA WL, LAI HC, YEH S, et al.Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis[J].Endocr Relat Cancer, 2014, 21 (3) :r165-r182. [47]DIEUDONNE M, PECQUERY R, BOUMEDIENE A, et al.Androgen receptors in human preadipocytes and adipocytes:Regional specificities and regulation by sex steroids[J].Am JPhysiol, 1998, 274 (6 Pt 1) :c1645-c1652. [48]VASSILATOU E, LAFOYIANNI S, VRYONIDOU A, et al.Increased androgen bioavailability is associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome[J].Hum Reprod, 2010, 25 (1) :212-220. [49]MU Y, SHE R, ZHANG H, et al.Effects of estrogen and androgen deprivation on the progression of non-alcoholic steatohepatitis (NASH) in male Sprague-Dawley rats[J].Hepatol Res, 2010, 39 (9) :910-920. [50]LUO FQ, MASATOSHI I, KOICHI A, et al.Raloxifene ameliorates liver fibrosis of nonalcoholic steatohepatitis induced by choline-deficient high-fat diet in ovariectomized mice[J].Dig Dis Sci, 2015, 60 (9) :2730-2739. [51]ASHER G, SASSONECORSI P.Time for food:The intimate interplay between nutrition, metabolism, and the circadian clock[J].Cell, 2015, 161 (1) :84-92. [52]KUTLU O, KALELI H, OZER E.Molecular pathogenesis of nonalcoholic steatohepatitis- (NASH-) related hepatocellular carcinoma[J].Can J Gastroenterol Hepatol, 2018, 2018:8543763. [53]BERNSMEIER C, WEISSKOPF D, PFLUEGER M, et al.Sleep disruption and daytime sleepiness correlating with disease severity and insulin resistance in non-alcoholic fatty liver disease:A comparison with healthy controls[J].PLo S One, 2015, 10 (11) :e0143293.
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