國家衛生研究院 NHRI:Item 3990099045/10782
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    题名: Serum soluble programmed cell death 1 level as a key predictor for spontaneous functional cure of chronic hepatitis B patients
    作者: Hu, HH;Pan, MH;Luo, WS;Chang, CL;Jeng, RWJ;Huang, YT;Su, CY;Chiang, CT;Jen, CL;Lu, SN;Wang, LY;Huang, LR;Shih, CH;Chen, CJ;Yang, HI
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Background and aims: The functional cure, seroclearance of hepatitis B surface antigen (HBsAg), is a desired goal for patients with chronic hepatitis B (CHB), who often show weak or absent virus-specific immunity due to programmed cell death 1 (PD-1)-associated T cell exhaustion . We aim to assess soluble PD-1 (sPD-1) as a novel seromarker for spontaneous HBsAg seroclearance . Method: Baseline and follow-up serum level of sPD-1 was evalu ated in all 1,046 patients from the REVEAL-HBV study who were hepatitis B e antigen-seronegative with serum HBV DNA undetectability until HBsAg seroclearance or the end of follow-up . sPD-1 levels were categorized in four groups (≥4000, 536-3999, 125-535, <125 pg/mL) according to upper and lower limits, and median level of quantification . We used multiple regression analyses to assess associations of baseline sPD-1 level with HBsAg decline during follow-up, and of baseline sPD-1 and its reduction with spontaneous HBsAg seroclearance . Odds ratio (OR) and rate ratio (RR) with 95% confidence interval (95% CI) were used to estimate magnitudes of associations . Results: A total of 390 patients achieved spontaneous HBsAg seroclearance during a mean 5 .4 years of follow-up . Baseline sPD-1 levels were correlated with qHBsAg levels (P<0 .0001), and associated with decline in HBsAg during follow-up (OR (95% CI) for ≥0 .5 log annual decline= 4 .7 (1 .7-12 .8), P=0 .002 for baseline sPD-1 <536 vs . ≥4000 pg/ mL) . Incidence rates of spontaneous HBsAg seroclearance increased with decreasing levels of baseline sPD-1 from 11 .5, 61 .7, 96 .7, to 151 .0 per 1000 person-years for sPD-1 levels ≥4000, 536-3999, 125-535, and <125 pg/mL, respectively (P trend <0 .0001) . After adjustment for gender, age,and alanine aminotransferase level, the RR (95% CI) of HBsAg seroclearance was 5 .7 (3 .8-8 .6), 8 .9 (6 .0-13 .2), and 14 .6 (9 .9-21 .6), respectively, for baseline sPD-1 levels of 536-3999, 125-535, and <125 pg/mL compared to sPD-1 levels of ≥4000 pg/mL . Among patients with baseline sPD-1 levels ≥4000 pg/mL, those who reduced sPD-1 to <125 pg/mL during follow-up had an OR (95% CI) of HBsAg seroclearance of 68 .6 (13 .2-357 .4) compared to those who persistently had sPD-1 >125pg/mL . Four SNPs near the SDC4 gene were associated with baseline sPD-1 levels and subsequent HBsAg seroclearance in a genome-wide association analysis . Conclusion: Reduced sPD-1 levels strongly predict greater chance of HBsAg decline and HBsAg seroclearance in HBeAg-seronegative CHB patients with HBV DNA undetectability . This seromarker may help in patient stratification, and might be considered as a promising target for achieving functional cure for CHB patients .
    日期: 2017-10
    關聯: Hepatology. 2017 Oct;66(Suppl. 1, S1):97A.
    Link to: http://dx.doi.org/10.1002/hep.29500
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-9139&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000412089800170
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