Basic research on chronic hepatitis B virus infection and metabolic dysfunction： Advances and controversies

Borong YU; Yuanwen CHEN

doi:10.12449/JCH240302

Volume 40 Issue 3

Mar. 2024

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2024 > 40(3): 446-452

PDF( 732 KB)

Basic research on chronic hepatitis B virus infection and metabolic dysfunction： Advances and controversies

DOI: 10.12449/JCH240302

Borong YU,
Yuanwen CHEN^{,
,}

Department of Gastroenterology，Huadong Hospital Affiliated to Fudan University，Shanghai 200040，China

Research funding:

General Project of National Natural Science Foundation of China (82270620);

Project of Science and Technology Commission of Shanghai Municipality (22140901500)

More Information

Corresponding author: CHEN Yuanwen， chenywhdgi@fudan.edu.cn （ORCID： 0000-0003-4210-007X）
Received Date: 2023-11-21
Accepted Date: 2023-12-26
Published Date: 2024-03-20

Abstract

Abstract

Hepatitis B virus （HBV） is considered a “metabolic virus” that can influence a variety of metabolic processes. There is still a lack of definite conclusion on the association between chronic HBV infection and the various types of metabolic dysfunction， and little is known about the mechanism of the association of chronic HBV infection with the diseases characterized by metabolic disorder， such as metabolic syndrome， diabetes， and metabolic associated fatty liver disease. Currently it is believed that hepatitis B x gene （HBx）， derived from HBV genome， might play an important role in mediating systemic metabolic alterations after HBV infection， and HBx influences the metabolism of carbohydrates and lipids and causes metabolic dysfunction by retgulating the expression profiles of the key proteins such as PPARγ， C/EBPα， SREBP， and FATP2. Nonalcoholic fatty liver disease （NAFLD） is the most severe manifestation of metabolic dysfunction in the liver， and since both NAFLD and HBV infection can cause liver injury， the research on the interaction between them has attracted more and more attention， with controversies requiring further exploration. Therefore， this article elaborates on the research advances in chronic HBV infection and metabolic dysfunction， so as to provide ideas for subsequent studies.
- Hepatitis B Virus,
- Metabolic Syndrome,
- Non-alcoholic Fatty Liver Disease

FullText(HTML)

References(55)

References

[1]	SHLOMAI A, SHAUL Y. The“metabolovirus” model of hepatitis B virus suggests nutritional therapy as an effective anti-viral weapon[J]. Med Hypotheses, 2008, 71( 1): 53- 57. DOI: 10.1016/j.mehy.2007.08.032.
[2]	TANG L, COVERT E, WILSON E, et al. Chronic hepatitis B infection: a review[J]. JAMA, 2018, 319( 17): 1802- 1813. DOI: 10.1001/jama.2018.3795.
[3]	HOTAMISLIGIL GS. Inflammation and metabolic disorders[J]. Nature, 2006, 444( 7121): 860- 867. DOI: 10.1038/nature05485.
[4]	ALBERTI KG, ZIMMET P, SHAW J. Metabolic syndrome--a new world-wide definition. A consensus statement from the international diabetes federation[J]. Diabet Med, 2006, 23( 5): 469- 480. DOI: 10.1111/j.1464-5491.2006.01858.x.
[5]	AKHTAR S, JUSTICE LV, MORRISON CM, et al. Fictional first memories[J]. Psychol Sci, 2018, 29( 10): 1612- 1619. DOI: 10.1177/0956797618778831.
[6]	ALKHULAIFI F, DARKOH C. Meal timing, meal frequency and metabolic syndrome[J]. Nutrients, 2022, 14( 9). DOI: 10.3390/nu14091719.
[7]	LI Y, ZHAO Y, WU J. Serum HBV surface antigen positivity is associated with low prevalence of metabolic syndrome: A meta-analysis[J]. PLoS One, 2017, 12( 5): e0177713. DOI: 10.1371/journal.pone.0177713.
[8]	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.
[9]	CHIANG CH, HUANG KC. Association between metabolic factors and chronic hepatitis B virus infection[J]. World J Gastroenterol, 2014, 20( 23): 7213- 7216. DOI: 10.3748/wjg.v20.i23.7213.
[10]	WANG SH, YEH SH, LIN WH, et al. Identification of androgen response elements in the enhancer I of hepatitis B virus: a mechanism for sex disparity in chronic hepatitis B[J]. Hepatology, 2009, 50( 5): 1392- 1402. DOI: 10.1002/hep.23163.
[11]	ZHOU Y, CUI Y, DENG H, et al. Association between hepatitis B virus infection and metabolic syndrome: a retrospective cohort study in Shanghai, China[J]. BMC Public Health, 2014, 14: 516. DOI: 10.1186/1471-2458-14-516.
[12]	LI WC, LEE YY, CHEN IC, et al. Association between the hepatitis B and C viruses and metabolic diseases in patients stratified by age[J]. Liver Int, 2013, 33( 8): 1194- 1202. DOI: 10.1111/liv.12224.
[13]	TAN Y, ZHANG X, ZHANG W, et al. The influence of metabolic syndrome on the risk of hepatocellular carcinoma in patients with chronic hepatitis B infection in China[J]. Cancer Epidemiol Biomarkers Prev, 2019, 28( 12): 2038- 2046. DOI: 10.1158/1055-9965.EPI-19-0303.
[14]	PETERSEN MC, SHULMAN GI. Mechanisms of insulin action and insulin resistance[J]. Physiol Rev, 2018, 98( 4): 2133- 2223. DOI: 10.1152/physrev.00063.2017.
[15]	WANG CC, HSU CS, LIU CJ, et al. Association of chronic hepatitis B virus infection with insulin resistance and hepatic steatosis[J]. J Gastroenterol Hepatol, 2008, 23( 5): 779- 782. DOI: 10.1111/j.1440-1746.2007.05216.x.
[16]	LEE JG, LEE S, KIM YJ, et al. Association of chronic viral hepatitis B with insulin resistance[J]. World J Gastroenterol, 2012, 18( 42): 6120- 6126. DOI: 10.3748/wjg.v18.i42.6120.
[17]	WU YL, PENG XE, ZHU YB, et al. Hepatitis B virus X protein induces hepatic steatosis by enhancing the expression of liver fatty acid binding protein[J]. J Virol, 2016, 90( 4): 1729- 1740. DOI: 10.1128/JVI.02604-15.
[18]	KIM K, KIM KH, CHEONG J. Hepatitis B virus X protein impairs hepatic insulin signaling through degradation of IRS1 and induction of SOCS3[J]. PLoS One, 2010, 5( 3): e8649. DOI: 10.1371/journal.pone.0008649.
[19]	YIN W, CHEN B, YANG Y, et al. Association between maternal hepatitis B virus carrier and gestational diabetes mellitus: a retrospective cohort analysis[J]. Virol J, 2021, 18( 1): 226. DOI: 10.1186/s12985-021-01691-0.
[20]	ELKRIEF L, RAUTOU PE, SARIN S, et al. Diabetes mellitus in patients with cirrhosis: clinical implications and management[J]. Liver Int, 2016, 36( 7): 936- 948. DOI: 10.1111/liv.13115.
[21]	KINALSKI M, KUŹMICKI M, TELEJKO B, et al. Tumor necrosis factor-alpha system in patients with gestational diabetes[J]. Przegl Lek, 2006, 63( 4): 173- 175.
[22]	TILG H, ADOLPH TE, DUDEK M, et al. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity[J]. Nat Metab, 2021, 3( 12): 1596- 1607. DOI: 10.1038/s42255-021-00501-9.
[23]	YASUMOTO J, KASAI H, YOSHIMURA K, et al. Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors[J]. J Gen Virol, 2017, 98( 7): 1762- 1773. DOI: 10.1099/jgv.0.000813.
[24]	ALVES-BEZERRA M, COHEN DE. Triglyceride metabolism in the liver[J]. Compr Physiol, 2017, 8( 1): 1- 8. DOI: 10.1002/cphy.c170012.
[25]	CURRIE E, SCHULZE A, ZECHNER R, et al. Cellular fatty acid metabolism and cancer[J]. Cell Metab, 2013, 18( 2): 153- 161. DOI: 10.1016/j.cmet.2013.05.017.
[26]	ARAIN SQ, TALPUR FN, CHANNA NA, et al. Serum lipids as an indicator for the alteration of liver function in patients with hepatitis B[J]. Lipids Health Dis, 2018, 17( 1): 36. DOI: 10.1186/s12944-018-0683-y.
[27]	DITTHAROT K, JITTORNTAM P, WILAIRAT P, et al. Urinary metabolomic profiling in chronic hepatitis B viral infection using gas chromatography/mass spectrometry[J]. Asian Pac J Cancer Prev, 2018, 19( 3): 741- 748. DOI: 10.22034/APJCP.2018.19.3.741.
[28]	LAMONTAGNE RJ, CASCIANO JC, BOUCHARD MJ. A broad investigation of the HBV-mediated changes to primary hepatocyte physiology reveals HBV significantly alters metabolic pathways[J]. Metabolism, 2018, 83: 50- 59. DOI: 10.1016/j.metabol.2018.01.007.
[29]	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.
[30]	MIQUILENA-COLINA ME, LIMA-CABELLO E, SÁNCHEZ-CAMPOS S, et al. Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C[J]. Gut, 2011, 60( 10): 1394- 1402. DOI: 10.1136/gut.2010.222844.
[31]	HUANG J, ZHAO L, YANG P, et al. Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium[J]. Exp Cell Res, 2017, 358( 2): 360- 368. DOI: 10.1016/j.yexcr.2017.07.012.
[32]	SCHOEMAN JC, HOU J, HARMS AC, et al. Metabolic characterization of the natural progression of chronic hepatitis B[J]. Genome Med, 2016, 8( 1): 64. DOI: 10.1186/s13073-016-0318-8.
[33]	WANG Y, WU T, HU D, et al. Intracellular hepatitis B virus increases hepatic cholesterol deposition in alcoholic fatty liver via hepatitis B core protein[J]. J Lipid Res, 2018, 59( 1): 58- 68. DOI: 10.1194/jlr.M079533.
[34]	WANG Y, HAO J, LIU X, et al. The mechanism of apoliprotein A1 down-regulated by Hepatitis B virus[J]. Lipids Health Dis, 2016, 15: 64. DOI: 10.1186/s12944-016-0232-5.
[35]	ZHU C, ZHU H, SONG H, et al. Hepatitis B virus inhibits the in vivo and in vitro synthesis and secretion of apolipoprotein C3[J]. Lipids Health Dis, 2017, 16( 1): 213. DOI: 10.1186/s12944-017-0607-2.
[36]	QIAO L, LUO GG. Human apolipoprotein E promotes hepatitis B virus infection and production[J]. PLoS Pathog, 2019, 15( 8): e1007874. DOI: 10.1371/journal.ppat.1007874.
[37]	FANG H, JUDD RL. Adiponectin regulation and function[J]. Compr Physiol, 2018, 8( 3): 1031- 1063. DOI: 10.1002/cphy.c170046.
[38]	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.
[39]	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.
[40]	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.
[41]	TONG X, SONG Y, YIN S, et al. Clinical impact and mechanisms of hepatitis B virus infection concurrent with non-alcoholic fatty liver disease[J]. Chin Med J(Engl), 2022, 135( 14): 1653- 1663. DOI: 10.1097/CM9.0000000000002310.
[42]	LIU Q, MU M, CHEN H, et al. Hepatocyte steatosis inhibits hepatitis B virus secretion via induction of endoplasmic reticulum stress[J]. Mol Cell Biochem, 2022, 477( 11): 2481- 2491. DOI: 10.1007/s11010-021-04143-z.
[43]	GAUDIERI S, RAUCH A, PFAFFEROTT K, et al. Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy[J]. Hepatology, 2009, 49( 4): 1069- 1082. DOI: 10.1002/hep.22773.
[44]	ZHANG RN, PAN Q, ZHANG Z, et al. Saturated fatty acid inhibits viral replication in chronic hepatitis B virus infection with nonalcoholic Fatty liver disease by toll-like receptor 4-mediated innate immune response[J]. Hepat Mon, 2015, 15( 5): e27909. DOI: 10.5812/hepatmon.15(5)2015.27909.
[45]	PICCININ E, VILLANI G, MOSCHETTA A. Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: the role of PGC1 coactivators[J]. Nat Rev Gastroenterol Hepatol, 2019, 16( 3): 160- 174. DOI: 10.1038/s41575-018-0089-3.
[46]	MAO Y, DA L, TANG H, et al. Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway[J]. Biochem Biophys Res Commun, 2011, 415( 1): 68- 74. DOI: 10.1016/j.bbrc.2011.10.013.
[47]	ESLAM M, MANGIA A, BERG T, et al. Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes[J]. Hepatology, 2016, 64( 1): 34- 46. DOI: 10.1002/hep.28475.
[48]	WONG VW, WONG GL, CHU WC, et al. Hepatitis B virus infection and fatty liver in the general population[J]. J Hepatol, 2012, 56( 3): 533- 540. DOI: 10.1016/j.jhep.2011.09.013.
[49]	ZHU L, JIANG J, ZHAI X, et al. Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study[J]. Liver Int, 2019, 39( 1): 70- 80. DOI: 10.1111/liv.13933.
[50]	MINAKARI M, MOLAEI M, SHALMANI HM, et al. Liver steatosis in patients with chronic hepatitis B infection: host and viral risk factors[J]. Eur J Gastroenterol Hepatol, 2009, 21( 5): 512- 516. DOI: 10.1097/MEG.0b013e328326792e.
[51]	LI JZ, YE LH, WANG DH, et al. The identify role and molecular mechanism of the MALAT1/hsa-mir-20b-5p/TXNIP axis in liver inflammation caused by CHB in patients with chronic HBV infection complicated with NAFLD[J]. Virus Res, 2021, 298: 198405. DOI: 10.1016/j.virusres.2021.198405.
[52]	MA J, SUN T, PARK S, et al. The role of hepatitis B virus X protein is related to its differential intracellular localization[J]. Acta Biochim Biophys Sin(Shanghai), 2011, 43( 8): 583- 588. DOI: 10.1093/abbs/gmr048.
[53]	BAI PS, XIA N, SUN H, et al. Pleiotrophin, a target of miR-384, promotes proliferation, metastasis and lipogenesis in HBV-related hepatocellular carcinoma[J]. J Cell Mol Med, 2017, 21( 11): 3023- 3043. DOI: 10.1111/jcmm.13213.
[54]	XU Z, ZHAI L, YI T, et al. Hepatitis B virus X induces inflammation and cancer in mice liver through dysregulation of cytoskeletal remodeling and lipid metabolism[J]. Oncotarget, 2016, 7( 43): 70559- 70574. DOI: 10.18632/oncotarget.12372.
[55]	LU Y, YANG X, KUANG Q, et al. HBx induced upregulation of FATP2 promotes the development of hepatic lipid accumulation[J]. Exp Cell Res, 2023, 430( 1): 113721. DOI: 10.1016/j.yexcr.2023.113721.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (524) PDF downloads(145)

Basic research on chronic hepatitis B virus infection and metabolic dysfunction： Advances and controversies

DOI: 10.12449/JCH240302

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Basic research on chronic hepatitis B virus infection and metabolic dysfunction： Advances and controversies

DOI: 10.12449/JCH240302

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content