Effect of Anti-HBs on Mortality Among Resolved HBV Infection: a Population-Based Prospective Cohort Study

Shuai-Wen Huang; Xi-Tang Li; Chen Chen; Qin Ning; Jia-Quan Huang

doi:10.1007/s40121-023-00766-5

Effect of Anti-HBs on Mortality Among Resolved HBV Infection: a Population-Based Prospective Cohort Study

Infect Dis Ther. 2023 Mar;12(3):871-890. doi: 10.1007/s40121-023-00766-5. Epub 2023 Feb 8.

Authors

Shuai-Wen Huang¹, Xi-Tang Li^{1

2}, Chen Chen³, Qin Ning^{1

2}, Jia-Quan Huang^{4

5}

Affiliations

¹ Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
² National Medical Center for Major Public Health Events, Wuhan, China.
³ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁴ Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. huangjiaquan21@aliyun.com.
⁵ National Medical Center for Major Public Health Events, Wuhan, China. huangjiaquan21@aliyun.com.

Abstract

Introduction: Surveillance programs after hepatitis B surface antigen (HBsAg) loss are not yet well established, and the role of hepatitis B surface antibodies (anti-HBs) remains controversial. We aimed to evaluate the risk factors for increased mortality and the association between anti-HBs and all-cause and cause-specific mortality in a representative US (United States) population of patients with resolved HBV (Hepatitis B virus) infections.

Methods: Data were taken from the US National Health and Nutrition Examination Survey (NHANES) 1999-2018. A total of 3455 US adults with resolved HBV infection [defined as hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive] were enrolled in this study. The primary outcome measures were all-cause and cause-specific mortality from baseline until 31 December 2019.

Results: During a mean follow-up of 10.3 years, 741 deaths occurred. Age, race, marital status, smoking status, physical activity level, and presence of cirrhosis, diabetes, cardiovascular diseases, chronic obstructive pulmonary diseases, cancer, and anti-HBs were significant factors for increased mortality, and a nomogram tool was developed and validated for the risk stratification of mortality. Compared with participants who were anti-HBs positive, those who were anti-HBs negative had a 23% (hazard ratio 1.23, 95% CI 1.02-1.46) higher risk of all-cause mortality in NHANES 1999-2018. For cause-specific mortality, the fully adjusted hazard ratios of participants who were anti-HBs negative were 0.71 (95% CI 0.48-1.06) for heart disease, 1.44 (95% CI 1.01-2.05) for cancer, and 1.44 (95% CI 1.13-1.83) for other conditions, compared to those of participants who were anti-HBs positive.

Conclusions: Among US adults with resolved HBV infections, anti-HBs-negative status was associated with an increased risk of death from all causes and cancer, implying that the role of anti-HBs in resolved HBV infection should not be ignored. On the public health level, more rigorous surveillance was needed for populations of individuals who were isolated anti-HBc positive.

Keywords: Antibody to hepatitis B surface antigen; Hepatitis B surface antigens loss; Immunity, Humoral; Mortality; Prognosis; Resolved HBV infection; Surveillance.