Noninvasive diagnostic indicators for histologically defined immune tolerance state in patients with chronic HBV infection and establishment and assessment of related models

Xinyu DU; Jia LI; Bei JIANG; Kunyu ZHAO; Yue HU; Fengmei WANG; Fengmin LU

doi:10.12449/JCH241208

Volume 40 Issue 12

Dec. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(12): 2392-2398

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Noninvasive diagnostic indicators for histologically defined immune tolerance state in patients with chronic HBV infection and establishment and assessment of related models

DOI: 10.12449/JCH241208

Xinyu DU¹,
Jia LI^2a,
Bei JIANG^2b,
Kunyu ZHAO³,
Yue HU^2b,
Fengmei WANG^{4
,
,
,},
Fengmin LU^{1, 5
,
,
,}

1.
Precision Medicine Center，Academy of Medical Sciences，Zhengzhou University，Zhengzhou 450052，China
2a.
Department of Liver Disease Tianjin 300192，China
2b.
Tianjin Hepatopathy Research Institute，Tianjin Second People’s Hospital，Tianjin 300192，China
3.
Peking University People’s Hospital，Peking University Hepatology Institute，Beijing 100044，China
4.
Department of Hepatology，Tianjin First Central Hospital，Tianjin 300192，China
5.
Department of Microbiology & Infectious Disease Center，School of Basic Medical Sciences，Peking University Health Science Center，Beijing 100191，China

Research funding:

National Natural Science Foundation of China (82372235);

National Natural Science Foundation of China (62301362);

Tianjin Key Medical Discipline Construction Project (TJYXZDXK-059B)

More Information

Corresponding author: WANG Fengmei， wangfengmeitj@126.com （ORCID： 0000-0001-9287-4183）; LU Fengmin， lu.fengmin@hsc.pku.edu.cn （ORCID： 0000-0002-1832-3209）
Received Date: 2024-03-20
Accepted Date: 2024-06-21
Published Date: 2024-12-25

Abstract

Abstract

Objective The natural history of chronic HBV infection often involves a histologically defined immune tolerance state， and once such immune tolerance state is broken， antiviral therapy should be initiated immediately. This study aims to investigate the correlation between immune-mediated liver injury and virological indicators for HBV and precisely identify the patients with a histologically defined immune tolerance state. Methods This study was conducted among 577 HBeAg-positive chronic hepatitis B （CHB） patients with HBV DNA >2×10⁶ IU/mL who did not receive antiviral therapy in The Fifth Medical Center of PLA General Hospital， Tianjin Second People’s Hospital， Shanghai Ruijin Hospital， and Taizhou Hospital of Zhejiang Province from January 2010 to December 2022. Liver biopsy was performed to determine the extent of liver injury， and the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and virological indicators were measured. The proportion of patients with a histologically defined immune tolerance state was analyzed based on the cut-off values of noninvasive indicators recommended in various guidelines， especially HBV load. In addition， a diagnostic model was established for the histologically defined immune tolerance state based on serum HBV DNA at the time when its correlation with liver immunopathological injury disappeared as the new threshold in combination with multiple indicators. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. The binary Logistic regression analysis was used to establish a multivariate diagnostic model； the area under the receiver operating characteristic curve （AUC） was used to investigate the diagnostic efficiency of different models， and the Z test was used for comparison of AUC. Results Among the patients with an immune tolerance state defined by the noninvasive indicators in the Chinese guidelines （2022 edition）， the EASL guidelines （2017 edition）， the AASLD guidelines （2018 edition）， and the APASL guidelines （2015 edition） for the prevention and treatment of CHB， the patients with a histologically defined immune tolerance state who met the definition in this article （HBV DNA>2×10⁶ IU/mL） accounted for 47.0%， 38.5%， 36.0%， and 44.6%， respectively， which did not exceed 50%. When the threshold of serum HBV DNA increased to >2×10⁸ IU/mL， although the correlation between immune-mediated liver injury and HBV DNA disappeared （r=-0.029， P=0.704）， the patients with a histologically defined immune tolerance state reached only 52.0%. In the cohort of 251 HBeAg-positive patients with serum HBV DNA >1×10⁸ IU/mL， there were significant differences in the levels of HBsAg， HBeAg， HBV DNA， ALT， and AST between the significant liver injury group with 140 children and the non-significant liver injury group with 111 patients （all P<0.05）， and the multivariate binary Logistic regression analysis showed that AST， HBV DNA， and HBeAg were influencing factors for histologically defined immune tolerance state in patients （all P<0.05）. Based on the above indicators and related clinical data， a predictive model was established as logit（P）=1.424－0.028×AST， with an AUC of 0.730， an optimal cut-off value of 30.5 U/L， a sensitivity of 52.8%， and a specificity of 84.1%. A total of 238 adult patients with chronic HBV infection who underwent liver biopsy in Taizhou Hospital of Zhejiang Province were enrolled as the validation cohort， and the analysis showed that the predictive model established in this study had a better efficiency than AST/ALT， FIB-4， and APRI， with an AUC of 0.698， 0.555， 0.518， and 0.373， respectively （all P<0.05）. Conclusion For HBeAg-positive patients with chronic HBV infection and HBV DNA>2×10⁸ IU/mL， an AST level of >30.5 U/L might indicate the “breakdown” of histologically defined immune tolerance state.
- Hepatitis B， Chronic,
- Immune Tolerance,
- Diagnosis

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References(15)

References

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Noninvasive diagnostic indicators for histologically defined immune tolerance state in patients with chronic HBV infection and establishment and assessment of related models

DOI: 10.12449/JCH241208

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Noninvasive diagnostic indicators for histologically defined immune tolerance state in patients with chronic HBV infection and establishment and assessment of related models

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