Chronic hepatitis B is caused by persistent hepatitis B virus infection and is commonly managed with long-term oral nucleos(t)ide analog therapy. Although these drugs can suppress viral replication in most adherent patients, loss of hepatitis B surface antigen, or HBsAg, remains uncommon during indefinite suppressive treatment. Add-on peginterferon alfa-2b is used in selected patients to stimulate an immune response that may promote HBsAg decline and increase the prospect of a functional cure, defined in the study as a step toward clearance rather than a guaranteed outcome. Its finite course can nevertheless be physically demanding: reported effects include fatigue, fever or chills, headache, muscle or joint pain, injection-site reactions, rash, itching, hair loss, appetite change, weight loss, sleep disturbance, mood symptoms and concern about blood-cell abnormalities.

The study recruited respondents from 1 to 13 May 2026 through hospital-based WeChat follow-up groups at West China Hospital of Sichuan University. Of 515 submitted questionnaires, 412 met the eligibility criteria: all had physician-diagnosed chronic hepatitis B, current or previous long-term oral antiviral treatment, and exposure to add-on peginterferon. At the time of the survey, 289 were receiving peginterferon, 84 had completed the recommended course and 39 reported premature discontinuation. The median age was 40 years, and 256 participants, or 62.1%, were men. Because investigators could not determine how many people received or viewed the invitation link, they could not calculate a formal response rate, making selection bias an important limitation.

Questionnaires assessed several domains with study-specific items: adverse-effect burden, belief in the need and value of treatment, physician–patient communication and a four-item persistence/value intention score covering willingness, confidence and willingness to tolerate discomfort to complete therapy. Adverse-effect burden was summarized from 15 items scored from 1 to 4, treatment belief from five items scored from 1 to 5, communication from three items scored from 1 to 5, and persistence/value intention from four items scored from 1 to 5. The Patient Health Questionnaire-4, or PHQ-4, separately measured anxiety, uncontrolled worry, loss of interest and depressed mood over the preceding two weeks on a scale of 0 to 12. Except for the PHQ-4, these measures were created for the study and were not formally pilot-tested or externally validated.

The most frequently reported moderate-to-severe effects or concerns were fatigue, affecting 37.1% of respondents, followed by rash or pruritus at 28.4%, alopecia at 27.4%, concern about leukocyte or platelet decline at 24.8%, myalgia or arthralgia at 24.0%, injection-site reactions at 22.3%, reduced appetite at 21.8%, worsened sleep at 20.6%, irritability at 18.9% and weight loss at 17.7%. Overall, 175 participants had wanted to stop peginterferon because of adverse effects, 136 had asked a physician about reducing the dose or stopping, and 39 reported actual premature discontinuation. Thus, thoughts of stopping were considerably more common than an all-cause early exit from therapy, which could also reflect a physician recommendation, perceived limited HBsAg response, inconvenience, cost or other reasons.

Multivariable logistic regression showed that each standard-deviation increase in the adverse-effect index was associated with higher odds of adverse-effect-related discontinuation thoughts, with an adjusted odds ratio of 1.86 and a 95% confidence interval of 1.37 to 2.51. Each standard-deviation increase in the PHQ-4 score was similarly associated with higher odds, with an adjusted odds ratio of 1.76 and a 95% confidence interval of 1.28 to 2.41. HBsAg feedback, oral antiviral duration, peginterferon duration, age and sex were not independently associated with those thoughts. Exploratory factor analysis separated the adverse-effect items into a broader symptom and daily-life component, including sleep, mood, skin, injection-site, laboratory and interference items, and a component dominated by fever or chills, fatigue, muscle or joint pain and headache. When both were entered together, only the broader component remained associated with discontinuation thoughts, indicating that the 15-item total should be interpreted as a heterogeneous burden index rather than a validated single dimension.

Psychological distress was also related to persistence/value intention among the 289 patients still receiving therapy. A stronger treatment-belief score was the largest positive correlate, with a standardized regression coefficient of 0.280 and a 95% confidence interval of 0.198 to 0.362. Better physician–patient communication had a smaller positive association, with a coefficient of 0.098 and a 95% confidence interval of 0.017 to 0.179, while higher PHQ-4 scores were associated with lower persistence/value intention, with a coefficient of −0.081 and a 95% confidence interval of −0.148 to −0.013. Adverse-effect burden and recalled HBsAg decline were not independently associated with the persistence score after adjustment. The model used heteroskedasticity-consistent HC3 standard errors because the intention score was bounded and concentrated toward its upper end.

Most participants recalled receiving an explanation of the treatment goal: 97.1% said they had been told that add-on peginterferon was intended to promote HBsAg decline or pursue clinical cure. In all, 76.9% knew their most recent HBsAg value and 95.9% knew either the value or its approximate trend; 78.2% reported that a physician had communicated an HBsAg decline. Yet these recalled messages were not independently associated with either discontinuation thoughts or persistence intention. The study did not verify laboratory results, and the coded feedback distinguished no decline or unclear feedback, a decline of uncertain magnitude and an obvious decline. The results therefore do not show that communicating HBsAg decline is ineffective; rather, they show that recalled decline feedback, as measured here, was not an independent correlate after accounting for other factors.

The distinction between intention and behavior is central to interpreting the results. Persistence/value intention was concentrated near the top of the five-point scale: 84.1% of currently treated respondents averaged at least 4, and 21.1% scored 5. Treatment belief and persistence intention were strongly correlated at 0.628 by Spearman’s rank correlation, and exploratory ordinal models supported partial rather than complete separation between them, indicating possible measurement overlap. Restricting the belief measure to three treatment-understanding items retained a positive association with persistence intention, with a standardized coefficient of 0.203. An exploratory interaction between belief and communication was not reproduced in sensitivity analyses and was therefore not treated as stable effect modification.

Several limitations constrain what can be concluded. The cross-sectional design does not establish temporal order or causality: the PHQ-4 captured symptoms only during the two weeks before questionnaire completion, whereas discontinuation thoughts could have occurred at any earlier point. The exploratory model of actual premature discontinuation contained only 39 events, and neither adverse-effect burden nor PHQ-4 score was independently associated with that all-cause outcome. Recruitment through hospital WeChat groups may also have favored patients more engaged in follow-up or more willing to remain in care. Although sensitivity analyses broadly supported the main associations in the 373 respondents who had not discontinued prematurely and in all 412 eligible participants, the findings remain associations in a selected survey population. Prospective studies are therefore needed to test whether structured education, symptom and distress screening and tiered follow-up improve treatment completion, ideally alongside verified HBsAg trajectories, missed injections, dose reductions and discontinuation records.

Subject of Research: Patient-reported treatment burden, communication and persistence during add-on peginterferon therapy for chronic hepatitis B

Article Title: Patient-reported treatment burden, communication, and persistence intention during add-on peginterferon alfa-2b therapy for chronic hepatitis B: a cross-sectional study

Article References: Han, N., Liu, H., Yan, L., & Tang, H. (2026). Patient-reported treatment burden, communication, and persistence intention during add-on peginterferon alfa-2b therapy for chronic hepatitis B: a cross-sectional study. Frontiers in Public Health, 14, Article 1972004. https://doi.org/10.3389/fpubh.2026.1972004

Image Credits: AI Generated

DOI: 10.3389/fpubh.2026.1972004

Keywords: chronic hepatitis B, peginterferon alfa-2b, treatment burden, treatment persistence, psychological distress, patient-reported outcomes, physician-patient communication, HBsAg decline, cross-sectional survey, Patient-reported, treatment, burden