HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat?

Sheng, Qiuju; Wang, Ning; Zhang, Chong; Fan, Yaoxin; Li, Yanwei; Han, Chao; Wang, Ziyi; Wei, Shuqi; Dou, Xiaoguang; Ding, Yang

doi:10.14218/jcth.2021.00443

Cited by 4 publications

(1 citation statement)

References 40 publications

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“…23 ALT is a sensitive indicator of hepatocellular injury and to some extent reflects the degree of hepatocyte damage and necrosis. 24 From the reports, chemokines interact with their receptors and play two sides in the disease process: One side mediates the aggregation and infiltration of inflammatory cells to the focus, playing an antiviral effect; on the other hand, they stimulate leukocytes and lymphocytes to release various degradative enzymes, oxygen free radicals, etc., leading to tissue and organ damage, further aggravating local inflammation and contributing to the chronification of hepatitis B. 25 At the same time, these activated cells may secrete more chemokines, which in turn mediate the aggregation of lymphocytes in liver tissue and participate in the inflammatory response.…”

Section: Gene Set Enrichment Analysismentioning

confidence: 99%

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

Yang,

Xu,

Cheng

et al. 2024

Journal of Medical Virology

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The serum chemokine C‐X‐C motif ligand‐10 (CXCL10) and its unique receptor (CXCR3) may predict the prognosis of patients with chronic hepatitis B (CHB) treated with tenofovir disoproxil fumarate (TDF). Nevertheless, there are few reports on the profile of CXCL10 and CXCR3 and their clinical application in HBeAg (+) CHB patients during TDF antiviral therapy. CXCL10 and CXCR3 were determined in 118 CHB patients naively treated with TDF for at least 96 weeks at baseline and at treatment weeks 12 and 24. In addition, gene set enrichment analysis was used to examine the associated dataset from Gene Expression Omnibus and explore the gene sets associated with HBeAg seroconversion (SC). The change of CXCL10 (ΔCXCL10, baseline to 48‐week TDF treatment) and CXCR3 (ΔCXCR3) is closely related to the possibility of HBeAg SC of CHB patients under TDF treatment. Immunohistochemical analysis of CXCL10/CXCR3 protein in liver tissue shows that there is a significant difference between paired liver biopsy samples taken before and after 96 weeks of successful TDF treatment of CHB patients (11 pairs) but no significance for unsuccessful TDF treatment (14 pairs). Multivariate Cox analysis suggests that the ΔCXCL10 is an independent predictive indicator of HBeAg SC, and the area under the receiver operating characteristic curve of the ΔCXCL10 in CHB patients is 0.8867 (p < 0.0001). Our results suggest that a lower descending CXCL10 level is associated with an increased probability of HBeAg SC of CHB patients during TDF therapy. Moreover, liver tissue CXCL10 might be involved in the immunological process of HBeAg SC.

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Section: Gene Set Enrichment Analysismentioning

confidence: 99%

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

Yang,

Xu,

Cheng

et al. 2024

Journal of Medical Virology

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Noninvasive serum markers for predicting significant liver histopathology in HBeAg-negative chronic HBV-infected patients with normal alanine aminotransferase

Gao,

Wang,

Liu

2024

Microbiol Spectr

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This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) and investigate noninvasive indicators for predicting significant liver histopathology. A total of 201 HBeAg-negative chronic HBV-infected patients with normal ALT who underwent liver biopsy were involved in this study. Significant liver histological changes were defined as necroinflammation grade ≥2 (G ≥ 2) and/or fibrosis stage ≥2 (S ≥ 2). The results showed that 42.3% (85/201) and 45.8% (92/201) of the HBeAg-negative patients with normal ALT have significant liver necroinflammation (G ≥ 2) and fibrosis (S ≥ 2), respectively. High normal ALT (>22 U/L), high level of serum HBV DNA (>3.42 log IU/mL), and low level of prealbumin (PA) (<170 mg/L) were independent predictors for significant liver necroinflammation, and the predictive value of the combined indicators was 0.750 ( P < 0.001), while high normal ALT (>24 U/L) and high level of FIB-4 (>1.53) were independent predictors for significant liver fibrosis, and the predictive value of the combined indicators was 0.740 ( P < 0.001). In conclusion, more than 40% of HBeAg-negative patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. ALT, PA, HBV DNA, and FIB-4 can independently predict significant liver inflammation and fibrosis for HBeAg-negative patients with normal ALT. Lowering the treatment threshold of ALT may benefit the HBeAg-negative chronic HBV-infected patients. IMPORTANCE Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) were supposed to have a low risk of progression to cirrhosis or hepatocellular carcinoma, and it was recommended to regularly follow up or undergo liver biopsy to assess liver histopathology according to the major international guidelines. However, this study indicates that a considerable number of HBeAg-negative chronic HBV-infected patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. Besides, several clinical commonly used noninvasive indicators were found that can be used to predict significant liver histopathology; thereby liver biopsy might be avoided for HBeAg-negative chronic HBV-infected patients with normal ALT.

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Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection

Ji,

Zhou,

Wang

et al. 2023

BMC Infect Dis

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Background Aberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. We aimed to explore the potential role of Wnt5a expression in liver injury caused by chronic HBV infection. Methods Wnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemical staining. Results Wnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to healthy controls and correlated positively with liver injury markers. Additionally, there was a significant correlation between Wnt5a mRNA expression and HBV DNA load in all patients and CHB patients but not in ACHBLF patients. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression compared with lower hepatic inflammatory grades. In addition, the cut-off value of 12.59 for Wnt5a mRNA level was a strong indicator in predicting ACHBLF in CHB patients. Conclusions We found that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in exacerbation of chronic HBV infection.

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HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat?

Cited by 4 publications

References 40 publications

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

Noninvasive serum markers for predicting significant liver histopathology in HBeAg-negative chronic HBV-infected patients with normal alanine aminotransferase

Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection

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