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  • Guo, Jianhui  (2)
  • Wu, Wennan  (2)
  • 1
    In: Cellular & Molecular Immunology, Springer Science and Business Media LLC, Vol. 18, No. 2 ( 2021-02), p. 461-471
    Abstract: Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNα therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-γ, TNF-α, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3 + CD8 + T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3 + CD8 + T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-α in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNα therapy by impairing the effector functions of CD3 + CD8 + T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-α responsiveness during CHB treatment.
    Type of Medium: Online Resource
    ISSN: 1672-7681 , 2042-0226
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2219471-X
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  • 2
    In: Journal of Clinical Laboratory Analysis, Wiley, Vol. 36, No. 11 ( 2022-11)
    Abstract: Though there are many advantages of pegylated interferon‐α (PegIFN‐α) treatment to chronic hepatitis B (CHB) patients, the response rate of PegIFN‐α is only 30 ~ 40%. Therefore, it is important to explore predictors at baseline and establish models to improve the response rate of PegIFN‐α. Methods We randomly divided 260 HBeAg‐positive CHB patients who were not previously treated and received PegIFN‐α monotherapy (180 μg/week) into a training dataset (70%) and testing dataset (30%). The intersect features were extracted from 50 routine laboratory variables using the recursive feature elimination method algorithm, Boruta algorithm, and Least Absolute Shrinkage and Selection Operator Regression algorithm in the training dataset. After that, based on the intersect features, eight machine learning models including Logistic Regression, k‐Nearest Neighbors, Support Vector Machine, Decision Tree, Random Forest, Gradient Boosting, Extreme Gradient Boosting (XGBoost), and Naïve Bayes were applied to evaluate HBeAg seroconversion in HBeAg‐positive CHB patients receiving PegIFN‐α monotherapy in the training dataset and testing dataset. Results XGBoost model showed the best performance, which had largest AUROC (0.900, 95% CI: 0.85–0.95 and 0.910, 95% CI: 0.84–0.98, in training dataset and testing dataset, respectively), and the best calibration curve performance to predict HBeAg seroconversion. The importance of XGBoost model indicated that treatment time contributed greatest to HBeAg seroconversion, followed by HBV DNA(log), HBeAg, HBeAb, HBcAb, ALT, triglyceride, and ALP. Conclusions XGBoost model based on common laboratory variables had good performance in predicting HBeAg seroconversion in HBeAg‐positive CHB patients receiving PegIFN‐α monotherapy.
    Type of Medium: Online Resource
    ISSN: 0887-8013 , 1098-2825
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2001635-9
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