合并非酒精性脂肪性肝病的慢性乙型肝炎患者HBV复制与脂代谢的相互影响

文夏杰; 李桂馨; 李婕; 饶慧瑛; 贾继东; 鲁凤民

doi:10.3969/j.issn.1001-5256.2021.07.002

合并非酒精性脂肪性肝病的慢性乙型肝炎患者HBV复制与脂代谢的相互影响

DOI: 10.3969/j.issn.1001-5256.2021.07.002

文夏杰¹,
李桂馨²,
李婕³,
饶慧瑛²,
贾继东⁴,
鲁凤民^{1, 2, ,}

1.
北京大学医学部基础医学院病原生物学系暨感染病中心，北京 100191
2.
北京大学人民医院肝病研究所，北京 100044
3.
山东大学附属省立医院感染性疾病科，济南 250021
4.
首都医科大学附属北京友谊医院肝病中心，北京 100050

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：鲁凤民参与文章设计及撰写；文夏杰、李桂馨参与文献检索、资料总结及文章撰写；贾继东、饶慧瑛、李婕参与修改文章关键内容。

详细信息

通信作者:
鲁凤民，lu.fengmin@hsc.pku.edu.cn

中图分类号: R512.62;R575.5
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- 被引次数: 0
出版历程
- 收稿日期: 2021-04-23
- 录用日期: 2021-04-23
- 出版日期: 2021-07-20

Interaction between hepatitis B virus replication and lipid metabolism in patients with chronic hepatitis B and NAFLD

1.
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
2.
Institute of Hepatology, People's Hospital, Peking University, Beijing 100044, China
3.
Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
4.
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

摘要

摘要: 慢性HBV感染者人数依然庞大，严重危害国人健康。而随着生活方式的改变，我国非酒精性脂肪性肝病(NAFLD)的发病率呈现逐年升高的趋势。部分临床研究显示，HBV感染并存NAFLD的发生率相对较低，但也有NAFLD促进慢性乙型肝炎相关疾病进展的报道。通过文献检索及综述，探究合并NALFD的慢性乙型肝炎患者中HBV复制与脂代谢异常及脂肪肝发生的相互影响，以期为HBV抗病毒治疗及预防NAFLD的发生提供思路。
- 乙型肝炎病毒 /
- 乙型肝炎，慢性 /
- 非酒精性脂肪性肝病 /
- 病毒复制
Abstract: There is still a large number of patients with chronic hepatitis B virus (HBV) infection in China, which greatly affects the health of Chinese people. With the change in lifestyle, the incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year in China. Some clinical studies have shown that there is a relatively low incidence rate of chronic HBV infection with NAFLD, while there are still reports on NAFLD in promoting the progression of chronic hepatitis B-related diseases. Based on literature search and review, this article attempts to investigate the interaction between HBV replication, abnormal lipid metabolism, and fatty liver disease in patients with chronic hepatitis B and NAFLD, in order to provide ideas for HBV antiviral treatment and prevention of NAFLD.
- Hepatitis B Virus /
- Hepatitis B /
- Non-alcoholic Fatty Liver Disease /
- Virus Replication

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参考文献(51)

[1]	Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[2]	ZHOU F, ZHOU J, WANG W, et al. Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: A systematic review and meta-analysis[J]. Hepatology, 2019, 70(4): 1119-1133. DOI: 10.1002/hep.30702.
[3]	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]. J Gastroenterol Hepatol, 2008, 23(9): 1419-1425. DOI: 10.1111/j.1440-1746.2008.05531.x.
[4]	JOO EJ, CHANG Y, YEOM JS, et al. Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: A cohort study[J]. Hepatology, 2017, 65(3): 828-835. DOI: 10.1002/hep.28917.
[5]	ZHONG GC, WU YL, HAO FB, et al. Current but not past hepatitis B virus infection is associated with a decreased risk of nonalcoholic fatty liver disease in the Chinese population: A case-control study with propensity score analysis[J]. J Viral Hepat, 2018, 25(7): 842-852. DOI: 10.1111/jvh.12878.
[6]	WANG B, LI W, FANG H, et al. Hepatitis B virus infection is not associated with fatty liver disease: Evidence from a cohort study and functional analysis[J]. Mol Med Rep, 2019, 19(1): 320-326. DOI: 10.3892/mmr.2018.9619.
[7]	XU QH, JIE YS, SHU X, et al. Relationship of fatty liver with HBV infection, hyperlipidemia and abnormal alanine aminotransferase[J]. Chin J Exp Clin Virol, 2009, 23(2): 141-143. DOI: 10.3760/cma.j.issn.1003-9279.2009.02.022. 徐启桓, 揭育胜, 舒欣, 等. 脂肪肝与HBV感染、高脂血症及ALT异常的相关分析[J]. 中华实验和临床病毒学杂志, 2009, 23(2): 141-143. DOI: 10.3760/cma.j.issn.1003-9279.2009.02.022
[8]	DANE DS, CAMERON CH, BRIGGS M. Virus-like particles in serum of patients with Australia-antigen-associated hepatitis[J]. Lancet, 1970, 1(7649): 695-698. DOI: 10.1016/s0140-6736(70)90926-8.
[9]	YAN H, ZHONG G, XU G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J]. Elife, 2012, 1: e00049. DOI: 10.7554/eLife.00049.
[10]	WANG WX, LI M, WU X, et al. HNF1 is critical for the liver-specific function of HBV enhancer Ⅱ[J]. Res Virol, 1998, 149(2): 99-108. DOI: 10.1016/s0923-2516(98)80085-x.
[11]	LI M, XIE Y, WU X, et al. HNF3 binds and activates the second enhancer, ENⅡ, of hepatitis B virus[J]. Virology, 1995, 214(2): 371-378. DOI: 10.1006/viro.1995.0046.
[12]	CHEN M, HIENG S, QIAN X, et al. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3[J]. Virology, 1994, 205(1): 127-132. DOI: 10.1006/viro.1994.1627.
[13]	GUIDOTTI LG, EGGERS CM, RANEY AK, et al. In vivo regulation of hepatitis B virus replication by peroxisome proliferators[J]. J Virol, 1999, 73(12): 10377-10386. DOI: 10.1128/JVI.73.12.10377-10386.1999.
[14]	REESE VC, OROPEZA CE, MCLACHLAN A. Independent activation of hepatitis B virus biosynthesis by retinoids, peroxisome proliferators, and bile acids[J]. J Virol, 2013, 87(2): 991-997. DOI: 10.1128/JVI.01562-12.
[15]	TANG H, MCLACHLAN A. Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism[J]. Proc Natl Acad Sci U S A, 2001, 98(4): 1841-1846. DOI: 10.1073/pnas.041479698.
[16]	BARDENS A, DÖRING T, STIELER J, et al. Alix regulates egress of hepatitis B virus naked capsid particles in an ESCRT-independent manner[J]. Cell Microbiol, 2011, 13(4): 602-619. DOI: 10.1111/j.1462-5822.2010.01557.x.
[17]	CHOU SF, TSAI ML, HUANG JY, et al. The dual role of an ESCRT-0 component HGS in HBV transcription and naked capsid secretion[J]. PLoS Pathog, 2015, 11(10): e1005123. DOI: 10.1371/journal.ppat.1005123.
[18]	JIANG B, HIMMELSBACH K, REN H, et al. Subviral hepatitis B virus filaments, like infectious viral particles, are released via multivesicular bodies[J]. J Virol, 2015, 90(7): 3330-3341. DOI: 10.1128/JVI.03109-15.
[19]	BREMER CM, BUNG C, KOTT N, et al. Hepatitis B virus infection is dependent on cholesterol in the viral envelope[J]. Cell Microbiol, 2009, 11(2): 249-260. DOI: 10.1111/j.1462-5822.2008.01250.x.
[20]	ABDUL-WAHED A, GUILMEAU S, POSTIC C. Sweet Sixteenth for ChREBP: Established roles and future goals[J]. Cell Metab, 2017, 26(2): 324-341. DOI: 10.1016/j.cmet.2017.07.004.
[21]	HAMILTON JA, KAMP F. How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids?[J]. Diabetes, 1999, 48(12): 2255-2269. DOI: 10.2337/diabetes.48.12.2255.
[22]	LUO J, YANG H, SONG BL. Mechanisms and regulation of cholesterol homeostasis[J]. Nat Rev Mol Cell Biol, 2020, 21(4): 225-245. DOI: 10.1038/s41580-019-0190-7.
[23]	BOUCHARD MJ, SCHNEIDER RJ. The enigmatic X gene of hepatitis B virus[J]. J Virol, 2004, 78(23): 12725-12734. DOI: 10.1128/JVI.78.23.12725-12734.2004.
[24]	KIM K, KIM KH, KIM HH, et al. Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRalpha[J]. Biochem J, 2008, 416(2): 219-230. DOI: 10.1042/BJ20081336.
[25]	KIM KH, SHIN HJ, KIM K, et al. Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARgamma[J]. Gastroenterology, 2007, 132(5): 1955-1967. DOI: 10.1053/j.gastro.2007.03.039.
[26]	KIM JY, SONG EH, LEE HJ, et al. HBx-induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-kappaB-dependent pathways[J]. J Mol Biol, 2010, 397(4): 917-931. DOI: 10.1016/j.jmb.2010.02.016.
[27]	PORSTMANN T, SANTOS CR, GRIFFITHS B, et al. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth[J]. Cell Metab, 2008, 8(3): 224-236. DOI: 10.1016/j.cmet.2008.07.007.
[28]	XIAO CX, YANG XN, HUANG QW, et al. ECHS1 acts as a novel HBsAg-binding protein enhancing apoptosis through the mitochondrial pathway in HepG2 cells[J]. Cancer Lett, 2013, 330(1): 67-73. DOI: 10.1016/j.canlet.2012.11.030.
[29]	OEHLER N, VOLZ T, BHADRA OD, et al. Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism[J]. Hepatology, 2014, 60(5): 1483-1493. DOI: 10.1002/hep.27159.
[30]	SHLOMAI A, PARAN N, SHAUL Y. PGC-1alpha controls hepatitis B virus through nutritional signals[J]. Proc Natl Acad Sci U S A, 2006, 103(43): 16003-16008. DOI: 10.1073/pnas.0607837103.
[31]	CURTIL C, ENACHE LS, RADREAU P, et al. The metabolic sensors FXRα, PGC-1α, and SIRT1 cooperatively regulate hepatitis B virus transcription[J]. FASEB J, 2014, 28(3): 1454-1463. DOI: 10.1096/fj.13-236372.
[32]	KIM HY, CHO HK, KIM HH, et al. Oxygenated derivatives of cholesterol promote hepatitis B virus gene expression through nuclear receptor LXRα activation[J]. Virus Res, 2011, 158(1-2): 55-61. DOI: 10.1016/j.virusres.2011.03.010.
[33]	ZENG J, WU D, HU H, et al. Activation of the liver X receptor pathway inhibits HBV replication in primary human hepatocytes[J]. Hepatology, 2020, 72(6): 1935-1948. DOI: 10.1002/hep.31217.
[34]	DU L, MA Y, LIU M, et al. Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo[J]. Virol J, 2017, 14(1): 96. DOI: 10.1186/s12985-017-0765-x.
[35]	HU W, WANG X, DING X, et al. MicroRNA-141 represses HBV replication by targeting PPARA[J]. PLoS One, 2012, 7(3): e34165. DOI: 10.1371/journal.pone.0034165.
[36]	WAKUI Y, INOUE J, UENO Y, et al. Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone[J]. Biochem Biophys Res Commun, 2010, 396(2): 508-514. DOI: 10.1016/j.bbrc.2010.04.128.
[37]	YOON S, JUNG J, KIM T, et al. Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor γ, controls hepatitis B virus replication[J]. Virology, 2011, 409(2): 290-298. DOI: 10.1016/j.virol.2010.10.024.
[38]	ZHANG Z, PAN Q, DUAN XY, et al. Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic mice model[J]. J Gastroenterol Hepatol, 2012, 27(12): 1858-1864. DOI: 10.1111/j.1440-1746.2012.07268.x.
[39]	HU D, WANG H, WANG H, et al. Non-alcoholic hepatic steatosis attenuates hepatitis B virus replication in an HBV-immunocompetent mouse model[J]. Hepatol Int, 2018, 12(5): 438-446. DOI: 10.1007/s12072-018-9877-7.
[40]	LIN YL, SHIAO MS, METTLING C, et al. Cholesterol requirement of hepatitis B surface antigen (HBsAg) secretion[J]. Virology, 2003, 314(1): 253-260. DOI: 10.1016/s0042-6822(03)00403-3.
[41]	DOROBANTU C, MACOVEI A, LAZAR C, et al. Cholesterol depletion of hepatoma cells impairs hepatitis B virus envelopment by altering the topology of the large envelope protein[J]. J Virol, 2011, 85(24): 13373-13383. DOI: 10.1128/JVI.05423-11.
[42]	HORIE M, TSUCHIYA Y, HAYASHI M, et al. NB-598: A potent competitive inhibitor of squalene epoxidase[J]. J Biol Chem, 1990, 265(30): 18075-18078. http://europepmc.org/abstract/MED/2211682
[43]	TATEMATSU K, TANAKA Y, SUGIYAMA M, et al. Host sphingolipid biosynthesis is a promising therapeutic target for the inhibition of hepatitis B virus replication[J]. J Med Virol, 2011, 83(4): 587-593. DOI: 10.1002/jmv.21970.
[44]	ZHANG JY, DUAN ZP, ZHANG JL, et al. Research advances in the role of sphingolipids in HCV and HBV life cycles[J]. Chin J Hepatol, 2016, 24(12): 945-947. DOI: 10.3760/cma.j.issn.1007-3418.2016.12.016. 张金艳, 段钟平, 张金兰, 等. 鞘脂在HCV和HBV生命周期中作用的研究进展[J]. 中华肝脏病杂志, 2016, 24(12): 945-947. DOI: 10.3760/cma.j.issn.1007-3418.2016.12.016.
[45]	HUANG Q, LEI H, DING L, et al. Stimulated phospholipid synthesis is key for hepatitis B virus replications[J]. Sci Rep, 2019, 9(1): 12989. DOI: 10.1038/s41598-019-49367-8.
[46]	PARK ES, LEE JH, HONG JH, et al. Phosphatidylcholine alteration identified using MALDI imaging MS in HBV-infected mouse livers and virus-mediated regeneration defects[J]. PLoS One, 2014, 9(8): e103955. DOI: 10.1371/journal.pone.0103955.
[47]	HUANG H, SUN Z, PAN H, et al. Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B[J]. Sci Rep, 2016, 6: 30853. DOI: 10.1038/srep30853.
[48]	LI H, ZHU W, ZHANG L, et al. The metabolic responses to hepatitis B virus infection shed new light on pathogenesis and targets for treatment[J]. Sci Rep, 2015, 5: 8421. DOI: 10.1038/srep08421.
[49]	GAVILANES F, GONZALEZ-ROS JM, PETERSON DL. Structure of hepatitis B surface antigen. Characterization of the lipid components and their association with the viral proteins[J]. J Biol Chem, 1982, 257(13): 7770-7777. http://www.ncbi.nlm.nih.gov/pubmed/7085648
[50]	OKAMURA H, NIO Y, AKAHORI Y, et al. Fatty acid biosynthesis is involved in the production of hepatitis B virus particles[J]. Biochem Biophys Res Commun, 2016, 475(1): 87-92. DOI: 10.1016/j.bbrc.2016.05.043.
[51]	ESSER K, LUCIFORA J, WETTENGEL J, et al. Lipase inhibitor orlistat prevents hepatitis B virus infection by targeting an early step in the virus life cycle[J]. Antiviral Res, 2018, 151: 4-7. DOI: 10.1016/j.antiviral.2018.01.001.