慢性乙型肝炎合并代谢相关脂肪性肝病的研究进展

殷珂; 宋玉芸; 刘峰

doi:10.12449/JCH241221

慢性乙型肝炎合并代谢相关脂肪性肝病的研究进展

DOI: 10.12449/JCH241221

北京大学人民医院，北京大学肝病研究所，丙型肝炎和肝病免疫治疗北京市重点实验室，非酒精性脂肪性肝病诊断北京市国际科技合作基地，北京 100044

基金项目:

国家自然科学基金 (82170584);

北京市自然科学基金 (7242151);

其敏计划

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：殷珂、宋玉芸负责文献检索，撰写文章；刘峰负责修改和审校文章。

详细信息

通信作者:
刘峰， liu1116m@sina.com （ORCID： 0000-0002-0316-4938）

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出版历程
- 收稿日期: 2024-03-28
- 录用日期: 2024-05-28
- 出版日期: 2024-12-25

Research advances in chronic hepatitis B with metabolic dysfunction-associated steatotic liver disease

Peking University People’s Hospital，Peking University Hepatology Institute，Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases，Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis，Beijing 100044，China

Research funding:

National Natural Science Foundation of China (82170584);

Beijing Natural Science Foundation (7242151);

Qimin Plan

More Information

Corresponding author: LIU Feng， liu1116m@sina.com （ORCID： 0000-0002-0316-4938）

摘要

摘要: 慢性乙型肝炎（CHB）和脂肪肝是我国常见的慢性肝脏疾病，随着生活方式的改变，CHB合并代谢相关脂肪性肝病的患者逐年增加，两种疾病均存在肝硬化、肝细胞癌（HCC）等不良事件发生的风险。二者共存时肝脏的病理生理学进程与单独的疾病状态可能不同，进而存在HBV的复制，HBsAg的血清学清除及抗病毒治疗受到影响，肝纤维化、HCC等不良事件风险增加的问题，故明确这些问题会对此类患者疾病的监测、治疗及预后有重要意义，本文将对这些问题的最新研究进展进行简要综述。
- 乙型肝炎，慢性 /
- 乙型肝炎病毒 /
- 脂肪肝
Abstract: Chronic hepatitis B （CHB） and fatty liver disease are common chronic liver diseases in China. With the changes in lifestyle， the number of patients with CHB and metabolic dysfunction-associated steatotic liver disease （MASLD） is increasing year by year. Both CHB and MASLD may lead to adverse events such as liver cirrhosis and hepatocellular carcinoma （HCC）. The pathophysiological course of the liver during the coexistence of the two diseases may be different from the state of each disease alone， and consequently HBV replication may exist， affecting HBsAg seroclearance and antiviral therapy and increasing the risk of adverse events including hepatic fibrosis and HCC. It is clear that these problems will be of great significance to the monitoring， treatment， and prognosis of such patients. Therefore， this article briefly reviews the latest research advances in these problems.
- Hepatitis B， Chronic /
- Hepatitis B Virus /
- Fatty Liver

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参考文献(58)

[1]	ZHANG XM, MA XQ, XU ZJ, et al. Effect of drug-resistant mutations in reverse transcriptase region of hepatitis B virus on the level of serum hepatitis B surface antigen[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2023, 17( 5): 324- 332. DOI: 10.3877/cma.j.issn.1674-1358.2023.05.006. 张小曼, 马筱秋, 许正锯, 等. 乙型肝炎病毒逆转录酶区耐药突变对血清乙型肝炎病毒表面抗原水平的影响[J/CD]. 中华实验和临床感染病杂志(电子版), 2023, 17( 5): 324- 332. DOI: 10.3877/cma.j.issn.1674-1358.2023.05.006.
[2]	COLLABORATORS PO. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: A modelling study[J]. Lancet Gastroenterol Hepatol, 2023, 8( 10): 879- 907. DOI: 10.1016/S2468-1253(23)00197-8.
[3]	Infectious Disease Physicians Branch of Chinese Medical Doctor Association, National Clinical Research Center for Infectious Diseases. Expert consensus on whole-population management of hepatitis B virus infection(2023)[J]. Chin J Clin Infect Dis, 2024, 17( 1): 1- 13. DOI: 10.3760/cma.j.issn.1674-2397.2024.01.001. 中国医师协会感染科医师分会, 国家感染性疾病临床医学研究中心. 乙型肝炎全人群管理专家共识(2023)[J]. 中华临床感染病杂志, 2024, 17( 1): 1- 13. DOI: 10.3760/cma.j.issn.1674-2397.2024.01.001.
[4]	RIAZI K, AZHARI H, CHARETTE JH, et al. The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2022, 7( 9): 851- 861. DOI: 10.1016/S2468-1253(22)00165-0.
[5]	ZHOU JH, ZHOU F, WANG WX, et al. Epidemiological features of NAFLD from 1999 to 2018 in China[J]. Hepatology, 2020, 71( 5): 1851- 1864. DOI: 10.1002/hep.31150.
[6]	YANG M, WEI L. Impact of NAFLD on the outcome of patients with chronic hepatitis B in Asia[J]. Liver Int, 2022, 42( 9): 1981- 1990. DOI: 10.1111/liv.15252.
[7]	SONG SJ, LAI JC, WONG GL, et al. Can we use old NAFLD data under the new MASLD definition?[J]. J Hepatol, 2024, 80( 2): e54- e56. DOI: 10.1016/j.jhep.2023.07.021.
[8]	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.
[9]	WANG MM, WANG GS, SHEN F, et al. Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors[J]. Dig Dis Sci, 2014, 59( 10): 2571- 2579. DOI: 10.1007/s10620-014-3180-9.
[10]	ZHOU R, YANG LP, ZHANG BB, et al. Clinical impact of hepatic steatosis on chronic hepatitis B patients in Asia: A systematic review and meta-analysis[J]. J Viral Hepat, 2023, 30( 10): 793- 802. DOI: 10.1111/jvh.13872.
[11]	SETO WK. Chronic hepatitis B and metabolic risk factors: A call for rigorous longitudinal studies[J]. World J Gastroenterol, 2019, 25( 3): 282- 286. DOI: 10.3748/wjg.v25.i3.282.
[12]	YILMAZ B, KOKLU S, BUYUKBAYRAM H, et al. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis[J]. Afr Health Sci, 2015, 15( 3): 714- 718. DOI: 10.4314/ahs.v15i3.3.
[13]	SHI YW, YANG RX, FAN JG. Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion[J]. World J Gastroenterol, 2021, 27( 26): 3971- 3983. DOI: 10.3748/wjg.v27.i26.3971.
[14]	HUANG JF, JING ML, WANG CY, et al. The impact of hepatitis B virus infection status on the prevalence of nonalcoholic fatty liver disease: A population-based study[J]. J Med Virol, 2020, 92( 8): 1191- 1197. DOI: 10.1002/jmv.25621.
[15]	CHENG YL, WANG YJ, KAO WY, et al. Inverse association between hepatitis B virus infection and fatty liver disease: A large-scale study in populations seeking for check-up[J]. PLoS One, 2013, 8( 8): e72049. DOI: 10.1371/journal.pone.0072049.
[16]	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.
[17]	CHEN JY, WANG JH, LIN CY, et al. Lower prevalence of hypercholesterolemia and hyperglyceridemia found in subjects with seropositivity for both hepatitis B and C strains independently[J]. J Gastroenterol Hepatol, 2010, 25( 11): 1763- 1768. DOI: 10.1111/j.1440-1746.2010.06300.x.
[18]	HUANG CY, LU CW, LIU YL, et al. Relationship between chronic hepatitis B and metabolic syndrome: A structural equation modeling approach[J]. Obesity, 2016, 24( 2): 483- 489. DOI: 10.1002/oby.21333.
[19]	ADOLPH TE, GRANDER C, GRABHERR F, et al. Adipokines and non-alcoholic fatty liver disease: Multiple interactions[J]. Int J Mol Sci, 2017, 18( 8): 1649. DOI: 10.3390/ijms18081649.
[20]	ZHANG JB, LIN SZ, JIANG DX, et al. Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors?[J]. Liver Int, 2020, 40( 3): 496- 508. DOI: 10.1111/liv.14369.
[21]	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.
[22]	LI J, LIANG X, JIANG J, et al. PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF[J]. Gut, 2022, 71( 1): 163- 175. DOI: 10.1136/gutjnl-2020-323395.
[23]	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.
[24]	QIU PS, WANG HZ, ZHANG MN, et al. FATP2-targeted therapies-A role beyond fatty liver disease[J]. Pharmacol Res, 2020, 161: 105228. DOI: 10.1016/j.phrs.2020.105228.
[25]	PEREZ VM, GABELL J, BEHRENS M, et al. Deletion of fatty acid transport protein 2(FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPARα-regulated genes[J]. J Biol Chem, 2020, 295( 17): 5737- 5750. DOI: 10.1074/jbc.RA120.012730.
[26]	LU Y, YANG XY, 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.
[27]	PELEG N, ISSACHAR A, SNEH ARBIB O, et al. Liver steatosis is a strong predictor of mortality and cancer in chronic hepatitis B regardless of viral load[J]. JHEP Rep, 2019, 1( 1): 9- 16. DOI: 10.1016/j.jhepr.2019.02.002.
[28]	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]. J Viral Hepat, 2018, 25( 1): 97- 104. DOI: 10.1111/jvh.12766.
[29]	CHU CM, LIN DY, LIAW YF. Does increased body mass index with hepatic steatosis contribute to seroclearance of hepatitis B virus(HBV) surface antigen in chronic HBV infection?[J]. Int J Obes(Lond), 2007, 31( 5): 871- 875. DOI: 10.1038/sj.ijo.0803479.
[30]	CHU CM, LIN DY, LIAW YF. Clinical and virological characteristics post HBsAg seroclearance in hepatitis B virus carriers with hepatic steatosis versus those without[J]. Dig Dis Sci, 2013, 58( 1): 275- 281. DOI: 10.1007/s10620-012-2343-9.
[31]	MAK LY, HUI RW, FUNG J, et al. Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B[J]. J Hepatol, 2020, 73( 4): 800- 806. DOI: 10.1016/j.jhep.2020.05.040.
[32]	SCHUSTER S, CABRERA D, ARRESE M, et al. Triggering and resolution of inflammation in NASH[J]. Nat Rev Gastroenterol Hepatol, 2018, 15( 6): 349- 364. DOI: 10.1038/s41575-018-0009-6.
[33]	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.
[34]	KHANMOHAMMADI S, KUCHAY MS. Toll-like receptors and metabolic(dysfunction)-associated fatty liver disease[J]. Pharmacol Res, 2022, 185: 106507. DOI: 10.1016/j.phrs.2022.106507.
[35]	TONG X, SONG Y, YIN SX, et al. Clinical impact and mechanisms of hepatitis B virus infection concurrent with non-alcoholic fatty liver disease[J]. Chin Med J, 2022, 135( 14): 1653- 1663. DOI: 10.1097/CM9.0000000000002310.
[36]	SETO WK, HUI RWH, MAK LY, et al. Association between hepatic steatosis, measured by controlled attenuation parameter, and fibrosis burden in chronic hepatitis B[J]. Clin Gastroenterol Hepatol, 2018, 16( 4): 575- 583. DOI: 10.1016/j.cgh.2017.09.044.
[37]	KHALILI M, KLEINER DE, KING WC, et al. Hepatic steatosis and steatohepatitis in a large North American cohort of adults with chronic hepatitis B[J]. Am J Gastroenterol, 2021, 116( 8): 1686- 1697. DOI: 10.14309/ajg.0000000000001257.
[38]	HUANG Y, GAN QY, LAI RT, et al. Application of fatty liver inhibition of progression algorithm and steatosis, activity, and fibrosis score to assess the impact of non-alcoholic fatty liver on untreated chronic hepatitis B patients[J]. Front Cell Infect Microbiol, 2021, 11: 733348. DOI: 10.3389/fcimb.2021.733348.
[39]	CHAN AW, WONG GL, CHAN HY, et al. Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B[J]. J Gastroenterol Hepatol, 2017, 32( 3): 667- 676. DOI: 10.1111/jgh.13536.
[40]	LIN M, GAO BW, PENG MN, et al. Metabolic dysfunction-associated steatotic liver disease increases hepatocellular carcinoma risk in chronic hepatitis B patients: A retrospective cohort study[J]. Front Physiol, 2024, 15: 1347459. DOI: 10.3389/fphys.2024.1347459.
[41]	HAN CL, TIAN BW, YANG CC, et al. The association of fatty liver and risk of hepatocellular carcinoma in HBV or HCV infected individuals: A systematic review and meta-analysis[J]. Expert Rev Gastroenterol Hepatol, 2023, 17( 2): 189- 198. DOI: 10.1080/17474124.2023.2166930.
[42]	LEE MH, CHEN YT, HUANG YH, et al. Chronic viral hepatitis B and C outweigh MASLD in the associated risk of cirrhosis and HCC[J]. Clin Gastroenterol Hepatol, 2024, 22( 6): 1275- 1285. DOI: 10.1016/j.cgh.2024.01.045.
[43]	LIM CT, GOH GBB, LI HH, et al. Presence of hepatic steatosis does not increase the risk of hepatocellular carcinoma in patients with chronic hepatitis B over long follow-up[J]. Microbiol Insights, 2020, 13: 1178636120918878. DOI: 10.1177/1178636120918878.
[44]	MAK LY, HUI RW, FUNG J, et al. Reduced hepatic steatosis is associated with higher risk of hepatocellular carcinoma in chronic hepatitis B infection[J]. Hepatol Int, 2021, 15( 4): 901- 911. DOI: 10.1007/s12072-021-10218-2.
[45]	HSUEH RC, WU WJ, LIN CL, et al. Impact of PNPLA3 p.I148M and hepatic steatosis on long-term outcomes for hepatocellular carcinoma and HBsAg seroclearance in chronic hepatitis B[J]. J Hepatocell Carcinoma, 2022, 9: 301- 313. DOI: 10.2147/JHC.S355540.
[46]	STREBA LA, VERE CC, ROGOVEANU I, et al. Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: An open question[J]. World J Gastroenterol, 2015, 21( 14): 4103- 4110. DOI: 10.3748/wjg.v21.i14.4103.
[47]	JIN X, CHEN YP, YANG YD, et al. Association between hepatic steatosis and entecavir treatment failure in Chinese patients with chronic hepatitis B[J]. PLoS One, 2012, 7( 3): e34198. DOI: 10.1371/journal.pone.0034198.
[48]	ZHANG SY, ZHANG XX, JIN HM, et al. Adverse effect of nonalcoholic fatty liver disease on the therapeutic response in patients with chronic hepatitis B[J]. J Clin Transl Hepatol, 2023, 11( 1): 67- 75. DOI: 10.14218/JCTH.2022.00066.
[49]	RUI FJ, GARCIA E, HU XY, et al. Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis[J]. J Viral Hepat, 2024, 31( 7): 372- 382. DOI: 10.1111/jvh.13942.
[50]	LI J, LE AK, CHAUNG KT, et al. Fatty liver is not independently associated with the rates of complete response to oral antiviral therapy in chronic hepatitis B patients[J]. Liver Int, 2020, 40( 5): 1052- 1061. DOI: 10.1111/liv.14415.
[51]	ZHU LY, WANG YG, WEI LQ, et al. The effects of the insulin resistance index on the virologic response to entecavir in patients with HBeAg-positive chronic hepatitis B and nonalcoholic fatty liver disease[J]. Drug Des Devel Ther, 2016, 10: 2739- 2744. DOI: 10.2147/DDDT.S114761.
[52]	ZHANG MY, CHEN SY, WU XN, et al. Persistent steatosis correlates with decreased fibrosis regression during anti-HBV treatment in patients with chronic HBV infection[J]. J Med Virol, 2023, 95( 10): e29156. DOI: 10.1002/jmv.29156.
[53]	MAK LY, SETO WK, HUI RW, et al. Fibrosis evolution in chronic hepatitis B e antigen-negative patients across a 10-year interval[J]. J Viral Hepat, 2019, 26( 7): 818- 827. DOI: 10.1111/jvh.13095.
[54]	GENG N, NI WJ, RUI FJ, et al. Chronic hepatitis B virus infection and metabolic associated fatty liver disease: The known and unknown aspects[J]. J Clin Hepatol, 2024, 40( 3): 441- 445. DOI: 10.12449/JCH240301. 耿楠, 倪文婧, 芮法娟, 等. 慢性HBV感染与代谢相关脂肪性肝病: 已知与未知[J]. 临床肝胆病杂志, 2024, 40( 3): 441- 445. DOI: 10.12449/JCH240301.
[55]	YOUNOSSI ZM, COREY KE, LIM JK. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: Expert review[J]. Gastroenterology, 2021, 160( 3): 912- 918. DOI: 10.1053/j.gastro.2020.11.051.
[56]	Resmetirom(Rezdiffra) for metabolic dysfunction-associated steatohepatitis[J]. Med Lett Drugs Ther, 2024, 66( 1701): 65- 66. DOI: 10.58347/tml.2024.1701a.
[57]	FRANCQUE SM, BEDOSSA P, RATZIU V, et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH[J]. N Engl J Med, 2021, 385( 17): 1547- 1558. DOI: 10.1056/NEJMoa2036205.
[58]	KIM JT, PARK MS, NAM TS, et al. Multiple cerebral arterial stenosis associated with hepatitis B virus infection[J]. J Clin Neurol, 2011, 7( 1): 40- 42. DOI: 10.3988/jcn.2011.7.1.40.