Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B.

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).

• Authors: Hui-Han Hu, Wen-Juei Jeng, Mei-Hung Pan, Wun-Sheng Luo, Chia-Ling Chang, Yen-Tsung Huang, Chien-Yu Su, Chen-Tse Chiang, Chin-Lan Jen, Yu-Chuan Chien, Shen-Nan Lu, Li-Yu Wang, Li-Rung Huang, Mei-Hsuan Lee, Jessica Liu, Mindie H Nguyen, Chien-Jen Chen, Hwai-I Yang
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 55 Issue 5 Pg. 558-567 (03 2022) ISSN: 1365-2036 [Electronic] England
• PMID: 35032052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• DNA, Viral
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Programmed Cell Death 1 Receptor

Topics

• Apoptosis
• DNA, Viral (genetics)
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (drug therapy)
• Humans
• Programmed Cell Death 1 Receptor