Liver histological changes and clinical features in chronic hepatitis B with normal or mildly elevated alanine aminotransferase
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摘要: 目的研究ALT水平正常或轻度升高的慢性乙型肝炎(CHB)患者肝组织学改变与临床指标的关系,为指导抗病毒治疗提供依据。方法回顾性收集四川省人民医院2011年10月-2018年8月行肝穿刺活检的CHB患者903例,比较性别、年龄、血清HBeAg状态、血清ALT、HBV DNA水平与ALT <2倍正常值上限(ULN) CHB患者肝脏炎症活动度和纤维化程度的关系,计数资料两组间比较采用χ2检验。结果 903例CHB患者肝脏炎症活动度分级在G1~G4之间,其中以G2为主,占67. 6%,G≥2的患者有831例(92. 0%);肝纤维化分期在S0~S4之间,以S1为主,占78. 2%,S≥2的患者有159例(17. 6%)。男性患者的肝脏炎症活动度分级和纤维化分期明显高于女性患者(χ2=6. 120、15. 098,P值均<0. 05)。ALT <1×ULN、1×ULN≤ALT <1. 5×ULN、ALT≥1. 5×ULN患者显著肝脏炎症坏死(G≥2)所占比例分别为91. 2%、92. 1%、94. 8%,差异有统计学意义(χAbstract: Objective To investigate the association between liver histological changes and clinical indices in chronic hepatitis B( CHB)patients with normal or mildly elevated alanine aminotransferase( ALT),and to provide a basis for guiding antiviral therapy. Methods A retrospective analysis was performed for the clinical data of 903 CHB patients who underwent liver biopsy in Sichuan Provincial People's Hospital from October 2011 to August 2018. The association of sex,age,serum HBeAg status,serum ALT,and HBV DNA level with liver inflammation activity and fibrosis degree was analyzed in CHB patients with an ALT level of < 2 × upper limit of normal( ULN). The chi-square test was used for comparison of categorical data between two groups. Results The liver inflammatory activity ranged from G1 to G4 in 903 CHB patients,among whom 67. 6% had G2 inflammation and 831( 92. 0%) had G≥2 inflammation; the fibrosis stage ranged from S0 to S4 in all patients,among whom 78. 2% had S1 fibrosis and 159( 17. 6%) had S≥2 fibrosis. Male patients had significantly higher liver inflammatory activity and fibrosis stage than the female patients( χ2= 6. 120 and 15. 098,both P < 0. 05). Among the patients with ALT < 1 × ULN,1 × ULN≤ALT < 1. 5 × ULN,and ALT≥1. 5 × ULN,91. 2%,92. 1%,and 94. 8%,respectively,had marked( G≥2)liver inflammation and necrosis,which showed a significant difference between the three groups( χ2= 28. 125,P < 0. 05); among the three groups of patients,12. 7%,22. 9%,and 24. 4%,respectively,had marked( S≥2) liver fibrosis,which showed a significant difference between the three groups( χ2= 18. 004,P < 0. 05). Liver inflammatory activity and fibrosis degree aggravated with the increase in the age of CHB patients( χ2= 65. 768 and 56. 056,both P < 0. 05) and the reduction in serum HBV DNA level( χ2= 21. 712 and 29. 461,both P <0. 05). The HBeAg-negative patients had significantly higher liver inflammatory activity and fibrosis stage than the HBeAg-positive patients( χ2= 30. 798 and 26. 380,both P < 0. 05). Among the HBeAg-positive and HBeAg-negative patients with an age of ≥30 years and 1. 5 × ULN ≤ ALT < 2 × ULN,100%( 40/40) and 97. 8%( 45/46),respectively,had marked liver inflammation and necrosis.Conclusion Most CHB patients with normal or mildly elevated ALT have marked liver inflammation and varying degrees of liver fibrosis,especially male patients aged ≥30 years. It is recommended to perform liver histopathological examination to assess the indication for antiviral therapy and avoid delay in treatment.
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Key words:
- hepatitis B,chronic /
- liver cirrhosis /
- pathology,clinical
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[1] OTT JJ,STEVENTS GA,GROEGER J,et al. Global epidemiology of hepatitis B virus infection:New estimates of agespecific HBsAg seroprevalence and endemicity[J]. Vaccine,2012,30(12):2212-2219. [2] SHEN FF,WANG Y,WANG YF,et al. Prediction of hepatic necroinflammatory activity in patients with chronic hepatitis B by a simple noninvasive model[J]. J Transl Med,2018,16(1):166. [3] ZHU XH,CHEN ZX,ZHUANG X,et al. Comparative effectiveness of prophylactic strategies for perinatal transmission of hepatitis B virus:A network Meta-analysis of randomized controlled tria[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition),2018,12(4):316-323.(in Chinese)朱晓红,陈智娴,庄勋,等.不同干预措施预防乙型肝炎病毒母婴传播的网络Meta分析[J/CD].中华实验和临床感染病杂志(电子版),2018,12(4):316-323. [4] Chinese Society of Hepatology and Chinese Society of Infectious Diseases Chinese,Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)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(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960. [5] CHENG JL,WANG XL,YANG SG,et al. Non-ALT biomarkers for markedly abnormal liver histology among Chinese persistently normal alanine aminotransferase chronic hepatitis B patients[J]. World J Gastroenterol,2017,23(15):2802-2810. [6] CHAO DT,LIM JK,AYOUB WS,et al. Systematic review with meta-analysis:The proportion of chronic hepatitis B patients with normal alanine transaminase≤40 IU/L and significant hepatic fibrosis[J]. Aliment Pharmacol Ther,2014,39(4):349-358. [7] WU Z,DONG X,WANG G,et al. Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal[J].J Viral Hepat,2019,26(2):287-296. [8] Chinese Society of Infectious Diseases and Parasitology,Chinese Society of Hepatology, Chinese Medical Association.Prevention and treatment of viral hepatitis[J]. Chin J Infect Dis,2001,19(1):56-62.(in Chinese)中华医学会传染病与寄生虫病学分会,肝病学分会.病毒性肝炎防治方案[J].中华传染病杂志,2001,19(1):56-62. [9] KUMAR M,SARIN SK,HISSAR S,et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT[J]. Gastroenterology,2008,134(5):1376-1384. [10] European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol,2017,67(2):370-398. [11] TERRAULT NA,BZOWEJ NH,CHANG KM,et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology,2016,63(1):261-283. [12] SARIN SK,KUMAR M,LAU GK,et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B:A 2015update[J]. Hepatol Int,2016,10(1):1-98. [13] GUI HL,WANG H,YANG YH,et al. Significant histopathology in Chinese chronic hepatitis B patients with persistently highnormal alanine aminotransferase[J]. J Viral Hepat,2010,17(1):44-50. [14] LIAO B,WANG Z,LIN S,et al. Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT[J]. PLo S One,2013,8(10):e78672. [15] SETO WK,LAI CL,IP PP,et al. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B[J]. PLo S One,2012,7(2):e32622. [16] SETO WK,WONG DK,FUNQ J,et al. High hepatitis B surface antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B[J]. PLo S One,2012,7(8):e43087. [17] MANSOUR-GHANAEI F,RAFIEI R,JOUKAR F,et al. Relationship between serum HBV DNA level and liver histology in HBV carriers with normal ALT in Guilan province,Iran[J].Med Sci Monit,2010,16(3):br97-br101.
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