Inactivated vaccines reduce the risk of liver function abnormality in NAFLD patients with COVID-19: a multi-center retrospective study

Zhixue Chen; Wenqing Tang; Nana Feng; Minzhi Lv; Fansheng Meng; Huibin Wu; Yitong Zhao; Huajie Xu; Yuxin Dai; Jindan Xue; Jingya Wang; Anjun Xu; Beilin Zhang; Dejie Chu; Yuqin Li; Dejun Wu; Ling Dong; Si Zhang; Ruyi Xue

doi:10.1016/j.ebiom.2023.104912

Inactivated vaccines reduce the risk of liver function abnormality in NAFLD patients with COVID-19: a multi-center retrospective study

EBioMedicine. 2024 Jan:99:104912. doi: 10.1016/j.ebiom.2023.104912. Epub 2023 Dec 13.

Authors

Zhixue Chen¹, Wenqing Tang¹, Nana Feng², Minzhi Lv³, Fansheng Meng⁴, Huibin Wu¹, Yitong Zhao⁵, Huajie Xu⁶, Yuxin Dai⁷, Jindan Xue⁵, Jingya Wang⁸, Anjun Xu⁹, Beilin Zhang¹⁰, Dejie Chu², Yuqin Li¹¹, Dejun Wu¹², Ling Dong¹³, Si Zhang¹⁴, Ruyi Xue¹⁵

Affiliations

¹ Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
² Department of Respiratory and Critical Medicine, Shanghai Eighth People's Hospital Affiliated to Jiang Su University, Shanghai, 200030, China.
³ Clinical Research Unit, Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Department of Biostatistics, Clinical Research Unit, Key Laboratory of Public Health Safety of Ministry of Education, Key Laboratory for Health Technology Assessment, National Commission of Health, School of Public Health, Center of Evidence-Based Medicine, Fudan University, Shanghai, 200032, China.
⁴ Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
⁵ School of Medicine, Anhui University of Science and Technology, Anhui, 232000, China.
⁶ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China.
⁷ NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
⁸ Department of Biochemistry and Molecular Biology, Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
⁹ Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
¹⁰ Department of Gastroenterology and Hepatology, Shanghai Baoshan District Wusong Central Hospital (Zhongshan Hospital Wusong Branch, Fudan University), Shanghai, 200940, China.
¹¹ Department of Gastroenterology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
¹² Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China; Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China. Electronic address: wudejun20565@163.com.
¹³ Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. Electronic address: dong.ling@zs-hospital.sh.cn.
¹⁴ NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. Electronic address: zhangsi@fudan.edu.cn.
¹⁵ Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Department of Gastroenterology and Hepatology, Shanghai Baoshan District Wusong Central Hospital (Zhongshan Hospital Wusong Branch, Fudan University), Shanghai, 200940, China. Electronic address: xue.ruyi@zs-hospital.sh.cn.

Abstract

Background: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19.

Methods: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness.

Findings: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings.

Interpretation: SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population.

Funding: 23XD1422700, Tszb2023-01, Zdzk2020-10, Zdxk2020-01, 2308085J27 and JLY20180124.

Keywords: COVID-19; Direct bilirubin; Inactivated SARS-CoV-2 vaccine; Liver function abnormality; Nonalcoholic fatty liver disease.

Publication types

Multicenter Study

MeSH terms

Bilirubin
COVID-19 Vaccines
COVID-19* / complications
COVID-19* / prevention & control
Humans
Non-alcoholic Fatty Liver Disease* / complications
Retrospective Studies
SARS-CoV-2
Vaccination
Vaccines, Inactivated

Substances

COVID-19 Vaccines
Bilirubin
Vaccines, Inactivated