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Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B
Hui-Han Hu 1 , Wen-Juei Jeng 1 2 , Mei-Hung Pan 1 , Wun-Sheng Luo 1 , Chia-Ling Chang 1 , Yen-Tsung Huang 1 , Chien-Yu Su 1 , Chen-Tse Chiang 1 , Chin-Lan Jen 1 , Yu-Chuan Chien 3 , Shen-Nan Lu 4 , Li-Yu Wang 1 , Li-Rung Huang 5 , Mei-Hsuan Lee 1 , Jessica Liu 6 , Mindie H Nguyen 6 , Chien-Jen Chen 1 , Hwai-I Yang 1 4
Affiliations
Affiliations
1
Taipei, Taiwan.
2
Taoyuan, Taiwan.
3
Taichung, Taiwan.
4
Kaohsiung, Taiwan.
5
Miaoli, Taiwan.
6
Palo Alto, California, USA.
PMID: 35032052 DOI: 10.1111/apt.16752
Abstract
Background: Hepatitis B surface antigen (HBsAg) seroclearance is the most important milestone indicating favourable clinical outcomes in patients with chronic hepatitis B (CHB). However, it is difficult to achieve due to the impaired HBV-specific immunity, such as programmed cell death 1 (PD-1)-associated T cell exhaustion. We assessed soluble PD-1 (sPD-1) as a novel seromarker for predicting spontaneous HBsAg loss.
Methods: Serial serum levels of sPD-1 were evaluated in 1046 untreated hepatitis B e antigen (HBeAg)-seronegative individuals who had achieved undetectable serum HBV DNA. Multiple regression analyses were applied to assess associations among baseline and subsequent sPD-1 levels, HBsAg decline during follow-up, and spontaneous HBsAg seroclearance.
Results: A total of 390 individuals achieved spontaneous HBsAg seroclearance during 6464.4 person-years of follow-up. Baseline sPD-1 levels were inversely associated with baseline HBsAg levels (qHBsAg) as well as a greater decline in qHBsAg during follow-up. Incidence rates of HBsAg seroclearance were 11.5, 61.7, 96.7 and 151.0 per 1000 person-years for sPD-1 levels of ≥4000, 536-3999, 125-535 and <125 pg/mL, respectively (Ptrend < 0.0001). Compared with baseline sPD-1 levels ≥4000 pg/mL, the rate ratio (95% CI) of HBsAg seroclearance was 2.1 (1.1-3.9), 3.0 (1.6-5.5) and 5.1 (2.8-9.5), for baseline sPD-1 levels of 536-3999, 125-535 and <125 pg/mL, respectively, after adjustment for sex, age and serum alanine aminotransferase and HBsAg levels.
Conclusion: sPD-1 level is a novel marker which independently predicts spontaneous HBsAg seroclearance of HBeAg-negative inactive CHB patients with undetectable HBV DNA. (word count: 234, <250).
© 2022 John Wiley & Sons Ltd. |
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