Which Is More Clinically Relevant: End-of-Treatment or Off-Treatment Predictors of Hepatitis B Relapse and Surface Antigen Loss?

We read with great interest the article by Sonneveld et al.1Sonneveld M. et al.Gastroenterology. 2023; Google Scholar The authors demonstrated that hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) levels at 24 weeks off treatment can predict clinical relapse and HBsAg loss in hepatitis B envelope antigen (HBeAg)–negative patients who discontinued anti-viral therapy. These findings can be used to guide patient management following nucleo(s)tide analogue (NUC) discontinuation. However, several issues require discussion. Firstly, identifying predictors at the end of treatment (EOT) is more clinically meaningful than predictors after therapy cessation. For patients undergoing long-term NUC therapy, the critical question we face is to decide whether to stop or continue NUC therapy. This should be based on the risk and benefit assessment of NUC therapy continuation vs discontinuation, which is generally evaluated at EOT rather than off treatment. Current guidelines recommend that discontinuation of NUC treatment requires a comprehensive evaluation of on-treatment parameters including HBeAg seroconversion, HBV DNA levels, duration of consolidation therapy, and so on. Therefore, we suggest that the authors shift focus to the predictors at the EOT in this cohort, which may provide more evidence that can be applied to clinical decision making. Second, the authors suggest that the findings of their study can be used to identify patients who may or may not require retreatment. However, no international consensus has been reached on whether and when to initiate anti-viral retreatment. Owing to the lack of sufficient high-level evidence, whether and when to retreat is based on the personal judgment of the physician. Moreover, re-treatment criteria have varied greatly among studies, ranging from HBV DNA >2000 IU/mL plus alanine transaminase (ALT) >2 upper limit of normal (ULN) to ALT >10× ULN or ALT >2× and ≤5× ULN and HBV DNA >20,000 IU/mL.2van Bömmel F. et al.J Hepatol. 2023; 78: 926-936Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar,3Fan R. et al.Clin Gastroenterol Hepatol. 2020; 18: 719-727.e7Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar Therefore, large-scale and long-term prospective studies should be conducted to compare the differences in prognosis between patients who received re-treatment and those who maintained NUC therapy cessation. Third, this study indicated that patients with lower HBsAg levels at 24 weeks off treatment have a better chance of achieving HBsAg loss. In fact, we have noticed during long-term follow-up that some patients with high HBsAg levels after treatment cessation also have the chance to achieve HBsAg loss. These patients generally experienced a rapid decrease of HBsAg levels after immune-mediated acute hepatitis flare.4García-López M. et al.J Hepatol. 2021; 74: 1064-1074Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar It would be interesting and meaningful to elucidate the common characteristics of such patients through multi-center collaboration and to reveal the underlying mechanisms. HBV DNA and HBsAg Levels at 24 Weeks Off-Treatment Predict Clinical Relapse and HBsAg Loss in HBeAg-Negative Patients Who Discontinued Antiviral TherapyGastroenterologyVol. 166Issue 1PreviewThe current multicenter study shows that blood levels of hepatitis B virus DNA and hepatitis B surface antigen at 24 weeks after withdrawal of antiviral treatment can predict subsequent outcomes. These findings can be used to identify patients who may or may not require retreatment. Full-Text PDF Open Access