• Shang-Chin Huang, Pin-Nan Cheng, Chen-Hua Liu, Hung-Chih Yang, Tung-Hung Su, Tai-Chung Tseng, Pei-Jer Chen, Jia-Horng Kao, and Chun-Jen Liu.
• Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan. Electronic address: chin780508@gmail.com.
• J Formos Med Assoc. 2022 May 1; 121 (5): 920-929.

Background/PurposeDirect-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting.MethodsFrom 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation).ResultsThere were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P < 0.05). Single or combination of these cytokines helped predict clinical reactivation (all P < 0.05).ConclusionHigher serum TNF-alpha at baseline and lower IFN-gamma at week 4 were associated with mild clinical reactivation of HBV in patients with HBV/HCV co-infection receiving DAAs. Combination of these cytokines reliably predicted HBV reactivation early.Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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