Work

Season-adjusted longitudinal changes in serum 25-hydroxyvitamin D during pegylated interferon add-on to ongoing tenofovir alafenamide therapy in chronic hepatitis B: a real-world cohort study

Year: 2026

Type: article

Abstract: Objectives To characterize serum 25-hydroxyvitamin D [25(OH)D] trajectories during peginterferon alfa-2b (Peg-IFN) add-on to ongoing tenofovir alafenamide (TAF) therapy in chronic hepatitis B and explore associations with hepatitis B surface antigen (HBsAg). Methods This retrospective cohort identified 203 consecutive patients, of whom 190 contributed longitudinal data through week 48. The primary random-intercept mixed-effects model used categorical visit time and adjusted for seasonality, age, and sex. Continuous-time, random-slope, visit-timing, and HBsAg-censoring analyses assessed sensitivity. Results The primary adjusted week-48 25(OH)D difference was −7.9 nmol/L (95% CI, −9.8 to −6.0) ( P < 0.001); the secondary continuous-time estimate was −8.3 nmol/L over 48 weeks. Observed concentrations declined through week 36 and partially rebounded at week 48. The proportion below 47.7 nmol/L increased from 21.1% to 34.7%. The adjusted total serum calcium trend was −0.061 mmol/L (95% CI, −0.074 to −0.049). Triglycerides increased while cholesterol fractions decreased. At week 48, 104/190 patients (54.7%) had an HBsAg decline of at least 1 log10 and 50/190 (26.3%) had visit-specific HBsAg loss. The concurrent 48-week change correlation was weak ( ρ = 0.150; FDR-adjusted P = 0.117), and the magnitude of 25(OH)D decline was not independently associated with either binary endpoint. Within patients, each 10 nmol/L increase in 25(OH)D was associated with a 0.068-log10 IU/mL increase in concurrent HBsAg (95% CI, 0.020 to 0.116; P = 0.006). Conclusions Serum 25(OH)D showed a non-linear decline during 48 weeks of follow-up, and the week-48 difference remained evident after adjustment for seasonality. However, without a concurrent comparator, the observed change cannot be attributed specifically to Peg-IFN, TAF, or their combination. Exploratory analyses suggested only a weak concurrent relationship between 25(OH)D and HBsAg, without evidence of prediction or causality. The clinical relevance of the observed changes in 25(OH)D and total serum calcium warrants further prospective investigation.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1976727

Authors: Ning Han, Huan Liu, Xia Zhu

Institutions: Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy

Language: English

Topic: Hepatitis B Virus Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801