Performance comparison of quantitative serum HBsAg and HBV DNA in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection

Abstract

Abstract: Objective To comparatively evaluate the performance of serum HBsAg and HBV DNA in predicting significant hepatitis activity in HBeAg-positive patients with chronic HBV infection. Methods 505 HBeAg-positive patients were enrolled. HBsAg and HBeAg were measured in an Abbott Architect I2000 automatic immunoassay system, HBV DNA was measured in a Roche LightCycler 480 qPCR system, and serum ALT was measured in an Abbott Architect C16000 automatic biochemical analysis system. Diagnoses of Liver pathological grade and stage referred to the Scheuer standard. Significant hepatitis activity was divided into three levels, which were successively defined as “ALT≥20 IU/L or (pathological grade>G1 or stage>S1)”, “ALT≥30 IU/L or (pathological grade>G1 or stage>S1)”, and “ALT≥40 IU/L or (pathological grade>G1 or stage>S1)”. Results According to LOESS regression analyses of ALT with HBsAg, HBeAg and HBV DNA, 279 patients were classified as possible high HBV replication population. In the total number of infected, the areas under ROC curve (AUCs) of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were successively 0.737 and 0.532, 0.737 and 0.548, and 0.686 and 0.545; in possible high HBV replication population, the AUCs of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were successively 0.866 and 0.544, 0.837 and 0.540, and 0.787 and 0.564. In both overall and possible high HBV replication population, the AUCs of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were all significantly greater than and all close to the area under diagonal reference line (all P<0.002 and all P>0.150); and the AUCs of HBsAg for predicting the three levels of significant hepatitis activity were all significantly greater than those of HBV DNA (P<0.001). With standard of HBsAg≤4.699 log10 IU/mL, the sensitivity and specificity of HBsAg for predicting significant hepatitis activity with ALT≥20 IU/L, ALT≥40 IU/L of overall population were 86.50% and 56.25%, 89.52% and 43.94%, respectively; and of possible high HBV replication population were 75.37% and 81.82%, 80.51% and 67.44%, respectively.Conclusion HBsAg has good performance and HBV DNA has no value in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection.

Key words: Hepatitis B surface antigen, Quantitative, Hepatitis B virus infection, Chronic, Natural history

LU Wei, ZHANG Zhan-qing, YAN Li, HUANG dan, LIN Wei-jia, ZHOU Xin-lan, DING Rong-rong, WANG Yan-bing, LI Xiu-fen. Performance comparison of quantitative serum HBsAg and HBV DNA in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection[J]. Chinese Hepatolgy, 2023, 28(1): 86-94.

References

[1] Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int, 2016, 10(1): 1-98.
[2] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol, 2017, 67(2): 370-398.
[3] Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology, 2018, 67(4): 1560-1599.
[4] 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版). 临床肝胆病杂志, 2019, 35(12): 2648- 2669.
[5] Normal limits of serum alanine aminotransferase in healthy population: A systematic review. Middle East J Dig Dis, 2020, 12(3): 194-205.
[6] Kumar M, Sarin SK, Hissar S, et al. Virological and histological features of chronic hepatitis B virus infected asymptomatic patients with persistently normal ALT. Gastroenterology, 2008, 134(5): 1376-1384.
[7] Gui HL, Wang H, Yang YH, et al. Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase. J Viral Hepat, 2010, 17 (Suppl. 1), 44-50.
[8] Liao B, Wang Z, Lin S, et al. Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT. PLoS ONE, 2013, 8(10): e78672.
[9] Xing YF, Zhou DQ, He JS, et al. Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China. PLoS ONE, 2018, 13(9): e0203220.
[10] Kumar M, Sarin SK. Hepatitis B virus immunotolerant patients: need to differentiate patients with or without liver disease. Gastroenterology, 2009, 137(2): 742-743.
[11] Zhang ZQ, Shi BS, Lu W, et al. Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients. Gastroenterol Hepatol, 2020, 43(9): 526-536.
[12] Cornberg M, Wong VWS, Locarnini S, et al. The role of quantitative hepatitis B surface antigen revisited. J Hepatol, 2017, 66(2): 398-411.
[13] Pollicino T, Caminiti G. HBV-integration studies in the clinic: Role in the natural history of infection. Viruses, 2021, 13(3): 368.
[14] Mak LY, Seto WK, Fung J, et al. Use of HBsAg quantification in the natural history and treatment of chronic hepatitis B. Hepatol Int, 2020, 14(1): 35-46.
[15] Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010, 52(4): 508-513.
[16] Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol, 2010, 52(4): 514-522.
[17] Zhang ZQ, Zhang XN, Lu W, et al. Distinct patterns of serum hepatitis B core-related antigen during the natural history of chronic hepatitis B. BMC Gastroenterol, 2017, 17(1): 140.
[18] Zhang ZQ, Wang YB, Lu W, et al. Performance of hepatitis B core-related antigen versus hepatitis B surface antigen and hepatitis B virus DNA in predicting HBeAg-positive and HBeAg-negative chronic hepatitis. Ann Lab Med, 2019, 39(1): 67-75.
[19] Brunt EM. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology, 2000, 31(1): 241-246.
[20] Milich DR. The concept of immune tolerance in chronic hepatitis B virus infection is alive and well. Gastroenterology, 2016, 151(5): 801-804.
[21] Han Q, Lan P, Zhang J, et al. Reversal of hepatitis B virus-induced systemic immunetolerance by intrinsic innate immune stimulation. J Gastroenterol Hepatol, 2013, 28 (Suppl. 1): 132-137.
[22] Guidotti LG, Isogawa M, Chisari FV. Host-virus interactions in hepatitis B virus infection. Curr Opin Immunol, 2015, 36: 61-66.
[23] Peeridogaheh H, Meshkat Z, Habibzadeh S, et al. Current concepts on immunopathogenesis of hepatitis B virus infection, Virus Research, 2018, 245: 29-43.
[24] Velazquez VM, Grakoui A. Immune quiescence and hepatitis B virus: Tolerance has its limits. Gastroenterology, 2012, 143(3): 529-532.
[25] Li TY, Yang Y, Zhou G, et al. Immune suppression in chronic hepatitis B infection associated liver disease: A review. World J Gastroenterol, 2019, 25(27): 3527-3537.
[26] Kramvis A, Kostaki EG, Hatzakis A, et al. Immunomodulatory function of HBeAg related to short-sighted evolution, transmissibility, and clinical manifestation of hepatitis B virus. Front Microbiol, 2018, 9: 2521.
[27] Mannan R, Misra V, Misra SP, et al. A comparative evaluation of scoring systems for assessing necro-inflammatory activity and fibrosis in liver biopsies of patients with chronic viral hepatitis. J Clin Diagn Res, 2014, 8(8): FC08-12.