Virological and immunological predictors of long term outcomes of peginterferon alfa-2a therapy for HBeAg-negative chronic hepatitis B.

Abstract

BACKGROUND/PURPOSE:

Predictors of long-term outcomes of peginterferon (PegIFN) therapy for patients with chronic hepatitis B (CHB) remain to be explored. This study aimed to evaluate the predictive value of virological and immunological biomarkers and outcomes of PegIFN for CHB.

METHODS:

57 HBeAg-negative CHB patients receiving 48 weeks of PegIFN therapy were prospectively followed for a median period of 5.3 years after the end of treatment (EOT). Serum CXCL9 and IP-10 levels were measured. Flow cytometry analysis for T cell subsets was performed in 23 patients. Factors associated with long-term outcomes were analyzed.

RESULTS:

The cumulative incidences of virological relapse, clinical relapse and HBsAg loss at year 7 were 18.1%, 0%, 31.6%, respectively, in patients with sustained off-treatment virological response (SVR), and 100%, 67.4%, 6.7%, respectively, in patients without SVR. By multivariate analysis, baseline CXCL9 > 80 pg/mL (hazard ratio (HR) = 0.418, p = 0.018) and on-treatment HBsAg declines were associated with a lower risk of virological relapse. Non-SVR was the only predictor of clinical relapse. CXCL9 >200 pg/mL (HR = 8.154, p = 0.038) and HBsAg <750 IU/mL (HR = 10.507, p = 0.036) were baseline predictors of HBsAg loss, while HBsAg decline >1 log at EOT (HR = 23.296, p = 0.005) was the on-treatment predictor of HBsAg loss. In subgroup patients with available PBMC, populations of T cell subsets correlated with virological and clinical relapses in univariate analysis.

CONCLUSION:

Baseline serum CXCL9 and HBsAg levels could predict HBsAg loss after PegIFN therapy for HBeAg-negative CHB. Combining virological and immunological biomarkers could predict long-term outcomes of PegIFN therapy for HBeAg-negative CHB.

• Authors: I-Cheng Lee, Chien-Wei Su, Keng-Hsin Lan, Yuan-Jen Wang, Kuei-Chuan Lee, Han-Chieh Lin, Ming-Chih Hou, Yi-Hsiang Huang
• Journal: Journal of the Formosan Medical Association = Taiwan yi zhi (J Formos Med Assoc) Vol. 120 Issue 9 Pg. 1676-1685 (Sep 2021) ISSN: 0929-6646 [Print] Singapore
• PMID: 33339708 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• peginterferon alfa-2a

Topics

• Antiviral Agents (therapeutic use)
• DNA, Viral
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Hepatitis B, Chronic (drug therapy)
• Humans
• Interferon-alpha
• Leukocytes, Mononuclear
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins (therapeutic use)
• Treatment Outcome