Hepatitis b infection: progress in identifying patients most likely to respond to peginterferon alfa

ABSTRACT

Introduction: Despite the disadvantage of side effects, pegylated interferon alpha (Peg-IFN α) remains an indispensable agent for chronic hepatitis B (CHB) due to its immunomodulatory effect. The selection of a patient most likely to have a favorable response becomes an essential issue for Peg-IFN α therapy.

Areas covered: Recent progress in the prediction of the treatment response to Peg-IFN α.

Expert opinion: Before Peg-IFN α therapy, baseline host and viral factors, including female sex, younger age, a high alanine aminotransferase level, HBV genotype A or B, and low viral load, predict a favorable response. In addition, on-treatment viral kinetics of hepatitis B surface antigen (HBsAg), e antigen (HBeAg) and HBV DNA help clinicians determine whether to continue or discontinue Peg-IFN α therapy. The novel HBV markers hepatitis B core-related antigen and HBV RNA have recently been investigated as useful predictors. The limited efficacy of Peg-IFN α monotherapy facilitated the development of new strategies of ‘add-on’ or ‘switch to’ Peg-IFN α in patients receiving long-term nucleot(s)ide analog treatment, which may lead to an increase in HBeAg and HBsAg loss. In summary, tailored Peg-IFN α therapeutic strategies based on predictors extended the landscape for CHB treatment.

KEYWORDS:

• Chronic hepatitis B
• hepatitis B virus
• pegylated interferon
• predictor
• response

Acknowledgments

This study was supported partially by Kaohsiung Medical University Research Center Grant (Center for Cancer Research KMU Global Networking Talent Plan Grant 105KMUOR08) and Kaohsiung Medical University Hospital (grant number KMUH108-8R08). The authors thank secretary help from Taiwan Liver Research Foundation (TLRF), Kaohsiung, Taiwan. They did not influence how the study was conducted or the approval of the manuscript. All the authors have read and approved the submitted manuscript.

Article highlights

• Peg-IFN α remains an indispensable anti-HBV agent, as it is the only agent that achieves a functional HBV cure.

• Host and viral predictors (baseline and on-treatment) of Peg-IFN α effectiveness as a treatment for HBV exist. The combination of these predictors further identifies patients with the most favorable response.

• Novel HBV markers, HBcrAg and HBV RNA, have recently been identified as promising predictors of Peg-IFN α therapy.

• Strategies of an ‘add-on’ or ‘switch to’ Peg-IFN α in patients already receiving steady NUC treatment obviously increase the treatment response. A careful consideration of the advantages and disadvantages before the application of these strategies is recommended.

• Physicians should consider all aspects of patients using the described predictors to obtain the optimal treatment strategy and response and to identify patients most likely to respond to Peg-IFN α.

Declaration of interest

Jee-Fu Huang consults for Roche, Sysmex, Gilead Sciences, PharmaEssentia, and has received honoraria from Bristol-Myers Squibb, Abbvie, Sysmex, Gilead Sciences, PharmaEssentia, Merck. Ming-Lung Yu has received research support (grant) from Abbott, BMS, Gilead and Merck; served as a consultant of Abbvie, Abbott, Ascletis, BMS, Gilead, Merck and Roche and served as a speaker of Abbvie, Abbott, BMS, Gilead, Merck, and IPSEN. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was funded in part by grants from Kaohsiung Medical University (Center for Cancer Research KMU Global Networking Talent Plan Grant 105KMUOR08), and Kaohsiung Medical University Hospital (grant number KMUH108-8R08).