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Hepatitis B core antibody and liver stiffness measurements predict HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with minimally elevated alanine aminotransferase (ALT) levels

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Abstract

Alanine aminotransferase (ALT) levels between 1 and 2 times the upper limit of normal (ULN) are common in patients with chronic hepatitis B (CHB) infection. There are few clinical studies focused on this group of patients because of the poorer treatment outcomes compared to those with more than 2 × ULN ALT level. However, treatments are necessary to reduce liver damage for patients with minimally elevated ALT levels. And biomarkers are needed in predicting the treatment response. In this study, a total of 106 patients with CHB were enrolled and treated with entecavir, telbivudine or tenofovir disoproxil fumarate. Liver stiffness was measured by transient elastography, and quantitative levels of hepatitis B core antibody (HBcAb) were detected by ELISA. At week 96, 31 (29.25%) patients achieved hepatitis B e antigen (HBeAg) seroconversion. Notably, baseline HBcAb levels and liver stiffness measurements (LSM) were higher in patients who achieved HBeAg seroconversion. The multivariate analysis showed that the baseline HBcAb levels and LSM were independent predictors for HBeAg seroconversion. The area under receiver operating characteristic curve of baseline HBcAb, LSM and the combination of them for HBeAg seroconversion was 0.714, 0.720 and 0.717, respectively. In addition, we discovered that the patients with baseline HBcAb levels ≥ 4.15 log10 IU/mL and LSM ≥ 9.85 kPa had higher rates of HBeAg seroconversion. Therefore, the measurement of HBcAb and liver stiffness might be good approaches for the optimization of antiviral therapy for HBeAg-positive CHB patients with minimally elevated ALT levels.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUROC:

Area under receiver operating characteristic curve

CHB:

Chronic hepatitis B

ETV:

Entecavir

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

HBeAg:

Hepatitis B e antigen

HBeAb:

Hepatitis B e antibody

HBcAb:

Hepatitis B core antibody

IFNs:

Interferons

kPa:

Kilopascals

LDT:

Telbivudine

LSM:

Liver stiffness measurement

NUCs:

Nucleos(t)ide analogues

ROC:

Receiver operating characteristic

SD:

Standard deviation

TBIL:

Total bilirubin

TDF:

Tenofovir disoproxil fumarate

TE:

Transient elastography

ULN:

Upper limit of normal

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Acknowledgements

This study was supported by Grant No. 201904010065 from the science and technology program of Guangzhou. We thank all patients, their families and nurses, for their kindly support.

Author information

Xihua Fu contributed to patient recruitment, acquisition and analysis of data, drafting of the manuscript and obtaining funding. Haibo Lou and Fang Chen contributed to patient recruitment and data collection. Xueping Gao and Zhanzhou Lin contributed to study concept and design, patient recruitment, interpretation of data, critical revision of the manuscript for important intellectual content. The article was approved to be published by all authors.

Correspondence to Xueping Gao or Zhanzhou Lin.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval and Informed consent

All procedures followed were in accordance with the Helsinki Declaration, and the study protocol was permitted by the Ethics Committee of Panyu Central Hospital, Guangzhou, China and Huizhou Municipal Central Hospital, Huizhou, China. Informed consents were signed by all patients.

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Fu, X., Lou, H., Chen, F. et al. Hepatitis B core antibody and liver stiffness measurements predict HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with minimally elevated alanine aminotransferase (ALT) levels. Clin Exp Med (2020). https://doi.org/10.1007/s10238-019-00603-5

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Keywords

  • Chronic hepatitis B
  • Minimally elevated ALT levels
  • Hepatitis B core antibody
  • Liver stiffness measurement