Reply.

Abstract

We thank Dr Lo for his interest in our recent article1Yeo Y.H. et al.Gastroenterology. 2019; 156: 635-646 e9Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar and his comments on the effect of treatments (antiviral agents and interferon-based therapy) on hepatitis B surface antigen (HBsAg) seroclearance. We agreed with Dr Lo that previous trials and meta-analyses have shown that interferon-treated patients had a high HBsAg seroclearance rate,2Marcellin P. et al.N Engl J Med. 2004; 351: 1206-1217Crossref PubMed Scopus (1057) Google Scholar, 3Qiu K. et al.Aliment Pharmacol Ther. 2018; 47: 1340-1348Crossref PubMed Scopus (38) Google Scholar but the generalizability of clinical trials is limited by their strict inclusion criteria and selection for patients who are more likely to respond and adhere to therapies. Therefore, to obtain a more realistic incidence rate of this key milestone in the natural history of hepatitis B infection, we excluded data from clinical trials. We found that the annual incidence rate of HBsAg seroclearance in untreated and treated patients was 1.31% (95% confidence interval, 0.98–1.67) and 0.82% (95% confidence interval, 0.34–1.50), respectively, compared with that of untreated patients. Furthermore, our systematic review only identified one article reporting the real-world annual incidence rate in interferon-α- or interferon-β-treated patients (HBsAg seroclerance rate; 1.80%; 95% confidence interval, 1.40–2.25),4Suzuki F. et al.J Gastroenterol. 2012; 47: 814-822Crossref PubMed Scopus (19) Google Scholar and part of the reason for the lack of real-world data may have to do with the significant side effect profile of pegylated interferon.5Konerman M.A. et al.Clin Liver Dis. 2016; 20: 645-665Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Therefore, although higher HBsAg seroclearance rates have been reported to be higher for pegylated interferon in prior clinical trials than the real-world data from our study,2Marcellin P. et al.N Engl J Med. 2004; 351: 1206-1217Crossref PubMed Scopus (1057) Google Scholar and we do appreciate Dr Lo’s comment about the value of pegylated interferon in inducing higher seroclearance rate of HBsAg in a subset of chronic HBV patients, the lack of optimism in our study conclusion regarding the incidence of HBsAg for the general real-world population of treated chronic hepatitis B patients was based on the available real-world data that we could evaluate. However, the available data are limited, and we do believe that additional studies with individual patient level data from large real-world cohorts that also include pegylated interferon patients are necessary to better evaluate HBsAg seroclearance rates for the various subsets of patients in routine practice, both treated and untreated. Therapy of Hepatitis B: Is It Really Not Associated With Hepatitis B Surface Antigen Seroclearance ?GastroenterologyVol. 157Issue 1PreviewI read with interest the study on factors associated with rates of hepatitis B surface antigen (HBsAg) clearance in adults with chronic hepatitis B virus (HBV) infection.1 This comprehensive review recognized some factors associated with the seroclearance of HBsAg. However, the therapy of HBV was not found to be an important factor for HBsAg loss. This point needs further clarification. Full-Text PDF