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慢性HBV感染重叠非酒精性脂肪性肝病的自然史、无创诊断及临床管理
DOI: 10.3969/j.issn.1001-5256.2021.07.003
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：徐亮起草并书写文章；宓余强设计文章思路并进行文稿审改；李萍参与文献分析；陈林参与文献检索。
Natural history and non-invasive diagnosis and clinical management of chronic HBV infection overlapping with nonalcoholic fatty liver disease
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摘要: 慢性HBV感染(CBI)重叠NAFLD情况日益普遍，而在重叠NAFLD对肝病自然史影响的研究中，多数认为重叠NAFLD促进了CBI患者肝硬化、肝细胞癌的发生，并促进了包括肝病死亡在内的全因死亡率，但也有研究得出了不同的结论；CBI重叠NAFLD时发生肝损伤的病因诊断是一个难题，金标准仍是肝组织病理，而探讨无创诊断方法意义重大；CBI重叠NAFLD需要在积极防治NAFLD的基础上根据现行CBI诊疗指南酌情进行抗HBV感染治疗。Abstract: Chronic HBV infection (CBI) overlapping with nonalcoholic fatty liver disease (NAFLD) is becoming more and more common. Most studies about the influence of overlapping with NAFLD on the natural history of CBI have shown that overlapping with NAFLD promotes not only the development of cirrhosis and hepatocellular carcinoma, but also all-cause mortality including death due to liver disease; however, some studies have reported different outcomes. The etiological diagnosis of liver injury in patients with CBI overlapping with NAFLD is a difficult issue in clinical practice, and liver histopathology is still the gold standard, while it is very important to explore noninvasive diagnostic methods. For patients with CBI overlapping with NAFLD, anti-HBV therapy should be given according to current diagnosis and treatment guidelines for CBI in addition to active prevention and treatment of NAFLD.
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Key words:
- Hepatitis B Virus /
- Hepatitis B, Chronic /
- Non-alcoholic Fatty Liver Disease /
- Diagnosis /
- Therapeutics
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[1] LEE JM, PARK YM, YUN JS, et al. The association between nonalcoholic fatty liver disease and esophageal, stomach, or colorectal cancer: National population-based cohort study[J]. PLoS One, 2020, 15(1): e0226351. DOI: 10.1371/journal.pone.0226351. [2] PERUMPAIL BJ, KHAN MA, YOO ER, et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2017, 23(47): 8263-8276. DOI: 10.3748/wjg.v23.i47.8263. [3] SETO WK, YUEN MF. Nonalcoholic fatty liver disease in Asia: Emerging perspectives[J]. J Gastroenterol, 2017, 52(2): 164-174. DOI: 10.1007/s00535-016-1264-3. [4] HUANG TD, BEHARY J, ZEKRY A. Non-alcoholic fatty liver disease: A review of epidemiology, risk factors, diagnosis and management[J]. Intern Med J, 2020, 50(9): 1038-1047. DOI: 10.1111/imj.14709. [5] HUI R, 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. [6] MAK LY, YUEN MF, SETO WK. Letter regarding "A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement"[J]. J Hepatol, 2020, 73(6): 1573-1574. DOI: 10.1016/j.jhep.2020.07.008. [7] 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. [8] WANG MF, LIN S, WU YL, et al. The correlation between fatty liver disease and serum and histological viral parameters in patients with chronic hepatitis B[J]. Chin J Infect Dis, 2016, 34(3): 141-145. DOI: 10.3760/cma.j.issn.1000-6680.2016.03.002.王明芳, 林苏, 吴银莲, 等. 慢性乙型肝炎患者肝脂肪变性与血清、肝组织病毒因素的关系[J]. 中华传染病杂志, 2016, 34(3): 141-145. DOI: 10.3760/cma.j.issn.1000-6680.2016.03.002. [9] FU YQ, LIU YG, XU L, et al. Analysis of clinical and pathological features of chronic hepatitis B with hepatic steatosis[J]. Chin J Hepatol, 2009, 17(11): 817-820. DOI: 10.3760/cma.j.issn.1007-3418.2009.11.006.宓余强, 刘勇钢, 徐亮, 等. 慢性乙型肝炎合并肝脂肪变的临床与病理学特征分析[J]. 中华肝脏病杂志, 2009, 17(11): 817-820. DOI: 10.3760/cma.j.issn.1007-3418.2009.11.006. [10] MI YQ, SHI QY, XU L, et al. Controlled attenuation parameter for noninvasive assessment of hepatic steatosis using Fibroscan®: Validation in chronic hepatitis B[J]. Dig Dis Sci, 2015, 60(1): 243-251. DOI: 10.1007/s10620-014-3341-x. [11] XU L, LU W, LI P, et al. A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B[J]. Dig Liver Dis, 2017, 49(8): 910-917. DOI: 10.1016/j.dld.2017.03.013. [12] 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. [13] 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. [14] HUANG J, JING M, WANG C, 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] 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. [16] CHIANG CH, LAI JS, HUNG SH, et al. Serum adiponectin levels are associated with hepatitis B viral load in overweight to obese hepatitis B virus carriers[J]. Obesity (Silver Spring), 2013, 21(2): 291-296. DOI: 10.1002/oby.20000. [17] 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. [18] 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. [19] 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. [20] KANG SK, CHUNG TW, LEE JY, et al. The hepatitis B virus X protein inhibits secretion of apolipoprotein B by enhancing the expression of N-acetylglucosaminyltransferase Ⅲ[J]. J Biol Chem, 2004, 279(27): 28106-28112. DOI: 10.1074/jbc.M403176200. [21] 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. [22] 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. [23] KARACAER Z, OKUR G, CERMIK H, et al. Is there an influence of hepatic steatosis on fibrosis and necroinflammation in young patients with chronic viral hepatitis B?[J]. Postgrad Med, 2016, 128(7): 697-700. DOI: 10.1080/00325481.2016.1221733. [24] CHOI H, BROUWER WP, ZANJIR W, et al. Nonalcoholic steatohepatitis is associated with liver-related outcomes and all-cause mortality in chronic hepatitis B[J]. Hepatology, 2020, 71(2): 539-548. DOI: 10.1002/hep.30857. [25] SCHUPPAN D, SURABATTULA R, WANG XY. Determinants of fibrosis progression and regression in NASH[J]. J Hepatol, 2018, 68(2): 238-250. DOI: 10.1016/j.jhep.2017.11.012. [26] CON D, CLAYTON-CHUBB D, LUBEL J, et al. Dynamics of liver stiffness in chronic hepatitis B patients with concurrent metabolic-associated fatty liver disease[J]. J Hepatol, 2021. DOI: 10.1016/j.jhep.2021.02.013.[Online ahead of print]. [27] ESLAM M, NEWSOME PN, SARIN SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement[J]. J Hepatol, 2020, 73(1): 202-209. DOI: 10.1016/j.jhep.2020.03.039. [28] WANG MF, WAN B, WU YL, et al. Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection[J]. World J Gastroenterol, 2021, 27(4): 336-344. DOI: 10.3748/wjg.v27.i4.336. [29] PAIS R, RUSU E, ZILISTEANU D, et al. Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease[J]. Eur J Intern Med, 2015, 26(1): 30-36. DOI: 10.1016/j.ejim.2014.12.001. [30] YU MW, LIN CL, LIU CJ, et al. Influence of metabolic risk factors on risk of hepatocellular carcinoma and liver-related death in men with chronic hepatitis B: A large cohort study[J]. Gastroenterology, 2017, 153(4): 1006-1017. e5. DOI: 10.1053/j.gastro.2017.07.001. [31] CHEN Y, FAN C, CHEN Y, et al. Effect of hepatic steatosis on the progression of chronic hepatitis B: A prospective cohort and in vitro study[J]. Oncotarget, 2017, 8(35): 58601-58610. DOI: 10.18632/oncotarget.17380. [32] 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. [33] LEE YB, HA Y, CHON YE, et al. Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B[J]. Clin Mol Hepatol, 2019, 25(1): 52-64. DOI: 10.3350/cmh.2018.0040. [34] LIM CT, GOH G, LI H, 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. [35] YOON JS, LEE HY, CHUNG SW, et al. Prognostic impact of concurrent nonalcoholic fatty liver disease in patients with chronic hepatitis B-related hepatocellular carcinoma[J]. J Gastroenterol Hepatol, 2020, 35(11): 1960-1968. DOI: 10.1111/jgh.15026. [36] CHENG JY, WONG VW, TSE YK, et al. Metabolic syndrome increases cardiovascular events but not hepatic events and death in patients with chronic hepatitis B[J]. Hepatology, 2016, 64(5): 1507-1517. DOI: 10.1002/hep.28778. [37] 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. [38] HANIF H, KHAN MM, ALI MJ, et al. A new endemic of concomitant nonalcoholic fatty liver disease and chronic hepatitis B[J]. Microorganisms, 2020, 8(10): 1526. DOI: 10.3390/microorganisms8101526. [39] MOTTIN CC, MORETTO M, PADOIN AV, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients[J]. Obes Surg, 2004, 14(5): 635-637. DOI: 10.1381/096089204323093408. [40] KARLAS T, PETROFF D, SASSO M, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis[J]. J Hepatol, 2017, 66(5): 1022-1030. DOI: 10.1016/j.jhep.2016.12.022. [41] FUJIWARA Y, KURODA H, ABE T, et al. The B-mode image-guided ultrasound attenuation parameter accurately detects hepatic steatosis in chronic liver disease[J]. Ultrasound Med Biol, 2018, 44(11): 2223-2232. DOI: 10.1016/j.ultrasmedbio.2018.06.017. [42] TADA T, ⅡJIMA H, KOBAYASHI N, et al. Usefulness of attenuation imaging with an ultrasound scanner for the evaluation of hepatic steatosis[J]. Ultrasound Med Biol, 2019, 45(10): 2679-2687. DOI: 10.1016/j.ultrasmedbio.2019.05.033. [43] REN X, XIA S, ZHANG L, et al. Analysis of liver steatosis analysis and controlled attenuation parameter for grading liver steatosis in patients with chronic hepatitis B[J]. Quant Imaging Med Surg, 2021, 11(2): 571-578. DOI: 10.21037/qims-19-1091. [44] BOHTE AE, van WERVEN JR, BIPAT S, et al. The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: A meta-analysis[J]. Eur Radiol, 2011, 21(1): 87-97. DOI: 10.1007/s00330-010-1905-5. [45] CAUSSY C, REEDER SB, SIRLIN CB, et al. Noninvasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials[J]. Hepatology, 2018, 68(2): 763-772. DOI: 10.1002/hep.29797. [46] LIANG J, LIU F, WANG F, et al. A noninvasive score model for prediction of NASH in patients with chronic hepatitis B and nonalcoholic fatty liver disease[J]. Biomed Res Int, 2017, 2017: 8793278. DOI: 10.1155/2017/8793278. [47] YANG RX, HU CX, SUN WL, et al. Serum monounsaturated triacylglycerol predicts steatohepatitis in patients with non-alcoholic fatty liver disease and chronic hepatitis B[J]. Sci Rep, 2017, 7(1): 10517. DOI: 10.1038/s41598-017-11278-x. [48] XU L, ZHONG Y, SU ST, et al. Study of reactive oxygen species and adiponectin for chronic HBV infection combined with nonalcoholic fatty liver diseases[J]. Chin J Hepatol, 2020, 28(3): 247-253. DOI: 10.3760/cma.j.cn501113-20191231-00486.徐亮, 钟燕, 苏淑婷, 等. 反应性氧化物、脂联素在慢性乙型肝炎病毒感染合并非酒精性脂肪性肝病中的研究[J]. 中华肝脏病杂志, 2020, 28(3): 247-253. DOI: 10.3760/cma.j.cn501113-20191231-00486. [49] ZHANG H, LI QY, GUO ZZ, et al. Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B[J]. World J Gastroenterol, 2012, 18(37): 5188-5196. DOI: 10.3748/wjg.v18.i37.5188. [50] LIU XL, PAN Q, ZHANG RN, et al. Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population[J]. World J Gastroenterol, 2016, 22(44): 9844-9852. DOI: 10.3748/wjg.v22.i44.9844. [51] LI Q, LU C, LI W, et al. The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty liver disease[J]. Oncotarget, 2017, 8(17): 28641-28649. DOI: 10.18632/oncotarget.16162. [52] ZHANG GL, XU SC, ZENG J, et al. Optimizing the use of the gamma-glutamyl transpeptidase-to-platelet ratio and transient elastography to identify liver cirrhosis in patients with chronic hepatitis B concurrent with nonalcoholic fatty liver disease[J]. Dis Markers, 2019, 2019: 2585409. DOI: 10.1155/2019/2585409. [53] XU N, XIE Q, LI J, et al. Improvement in liver stiffness measurement for diagnosis of liver fibrosis in patients with concurrent chronic hepatitis B and nonalcoholic fatty liver disease[J]. J Int Med Res, 2020, 48(2): 300060520903667. DOI: 10.1177/0300060520903667. [54] SHEN F, MI YQ, XU L, et al. Moderate to severe hepatic steatosis leads to overestimation of liver stiffness measurement in chronic hepatitis B patients without significant fibrosis[J]. Aliment Pharmacol Ther, 2019, 50(1): 93-102. DOI: 10.1111/apt.15298. [55] PARK CC, NGUYEN P, HERNANDEZ C, et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease[J]. Gastroenterology, 2017, 152(3): 598-607. e2. DOI: 10.1053/j.gastro.2016.10.026. [56] KIM DS, JEON MY, LEE HW, et al. Influence of hepatic steatosis on the outcomes of patients with chronic hepatitis B treated with entecavir and tenofovir[J]. Clin Mol Hepatol, 2019, 25(3): 283-293. DOI: 10.3350/cmh.2018.0054. [57] 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. [58] GONG L, LIU J, WANG J, et al. Hepatic steatosis as a predictive factor of antiviral effect of pegylated interferon therapy in patients with hepatitis B[J]. Transplant Proc, 2015, 47(10): 2886-2891. DOI: 10.1016/j.transproceed.2015.10.023. [59] CHEN YC, JENG WJ, HSU CW, et al. Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: A retrospective study[J]. BMC Gastroenterol, 2020, 20(1): 146. DOI: 10.1186/s12876-020-01289-w. [60] 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. -
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