Serum cytokine profiles predict outcomes of chronic hepatitis B patients discontinuing entecavir or tenofovir therapy

Meng-Ju Lin; Tung-Hung Su; Chun-Jen Liu; Hung-Chih Yang; Chi-Ling Chen; Jyh-Ming Liou; Tai-Chung Tseng; Chen-Hua Liu; Chun-Ming Hong; Pei-Jer Chen; Jia-Horng Kao

Journal of the Formosan Medical Association (Jul 2023)

Serum cytokine profiles predict outcomes of chronic hepatitis B patients discontinuing entecavir or tenofovir therapy

Meng-Ju Lin,
Tung-Hung Su,
Chun-Jen Liu,
Hung-Chih Yang,
Chi-Ling Chen,
Jyh-Ming Liou,
Tai-Chung Tseng,
Chen-Hua Liu,
Chun-Ming Hong,
Pei-Jer Chen,
Jia-Horng Kao

Affiliations

Meng-Ju Lin: School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Tung-Hung Su: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, 1 Chang-Te Street, Taipei 10048, Taiwan.
Chun-Jen Liu: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Hung-Chih Yang: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chi-Ling Chen: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Jyh-Ming Liou: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Tai-Chung Tseng: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chen-Hua Liu: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chun-Ming Hong: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Jia-Horng Kao: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, 1 Chang-Te Street, Taipei 10048, Taiwan.

Journal volume & issue: Vol. 122, no. 7
pp. 564 – 573

Abstract

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Background/purpose: Distinct hepatitis relapse has been observed after discontinuing entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients. End-of-therapy (EOT) serum cytokines were compared and used for outcome prediction. Methods: A total of 80 non-cirrhotic CHB patients in a tertiary medical center in Taiwan who discontinued ETV (n = 51) or TDF (n = 29) therapy after fulfilling the APASL guidelines were prospectively enrolled. Serum cytokines were measured at EOT and 3rd month afterwards. Multivariable analysis was performed to predict virological relapse (VR, HBV DNA >2000 IU/mL), clinical relapse (CR, VR and alanine aminotransferase > 2-fold upper limit of normal) and hepatitis B surface antigen (HBsAg) seroclearance. Results: Compared with TDF group, ETV stoppers had greater interleukin 5 (IL-5), IL-12 p70, IL-13, IL-17 A and tumor necrosis factor alpha (TNF-alpha) (all P < 0.05) at EOT. Older age, TDF use, higher EOT HBsAg and IL-18 (Hazard ratio [HR], 1.01; 95% CI, 1.00–1.02) levels at EOT predicted VR, while older age, higher EOT HBsAg and IL-7 (HR, 1.25; 95% CI, 1.00–1.56) levels predicted CR. In TDF stoppers, higher IL-7 (HR, 1.29; 95% CI, 1.05–1.60) and IL-18 (HR, 1.02; 95% CI, 1.00–1.04) levels predicted VR, while IL-7 (HR, 1.34; 95% CI, 1.08–1.65) and interferon-gamma (IFN-gamma) (HR, 1.08; 95% CI, 1.02–1.14) levels predicted CR. A lower EOT HBsAg level was associated with HBsAg seroclearance. Conclusion: Distinct cytokine profiles were observed after stopping ETV or TDF. Higher EOT IL-7, IL-18, and IFN-gamma could be probable predictors for VR and CR in patients discontinuing NA therapies.

Published in Journal of the Formosan Medical Association

ISSN: 0929-6646 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/journal-of-the-formosan-medical-association/

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