Prediction of Clinical Relapse and HBsAg Loss After Cessation of Anti-HBV Therapy

The study by Sonneveld et al1Sonneveld M. et al.Gastroenterology. 2023; PubMed Google Scholar reported analyses on the prediction of clinical relapse (CR) and hepatitis B surface antigen (HBsAg) loss based on hepatitis B virus (HBV) markers at 24 weeks after the end of therapy. There are several crucial points that require clarification and/or discussion.1.Studies have shown that up to >70% of CRs after tenofovir (TDF) withdrawal occur within 6 months, in contrast to >70% of CRs occurring beyond 6 months after entecavir (ETV) cessation.2Jeng W.J. et al.Clin Gastroenterol Hepatol. 2016; 14: 1813-1820Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 3Höner Zu Siederdissen C. et al.J Infect Dis. 2018; 218: 1480-1484Crossref PubMed Scopus (28) Google Scholar, 4Liu Y.C. et al.Liver Int. 2022; 42: 551-560Crossref PubMed Scopus (13) Google Scholar This may imply that the prediction of CR after 24 weeks following TDF cessation is of very limited value. Along this line, it is very possible that most of the 126 patients excluded from this study because of CR within 24 weeks are TDF-treated patients and thus may have inadvertently distorted the results after week 24 in the whole cohort including both ETV- and TDF-treated patients. Perhaps ETV- and TDF-treated patients need separate analyses to see how it turns out.2.End-of-therapy quantitative HBsAg, the lower the better, has been widely accepted as the best predictor of CR and HBsAg loss.5Jeng W.J. et al.Hepatology. 2018; 68: 425-434Crossref PubMed Scopus (200) Google Scholar The CR rate in patients with the combined markers of HBsAg >100 and HBV DNA >100 IU/mL looks no better than HBsAg >100 IU/mL alone (Fig. 3A vs Fig. 2A P values?). although the combined 2 markers showed greater HBsAg loss rate at 4 years. Notably, HBsAg loss rate increases more apparently after 4 years of off-therapy follow-up.6Hall S.A.L. et al.Gut. 2022; 71: 1629-1641PubMed Google Scholar Follow-up past 4 years would prove which is better for the prediction of HBsAg loss. In the first 2–4 years, prediction of CR is more important than HBsAg loss.3.The HBV DNA categorization does not seem appropriate in that the most important cutoff level of HBV DNA is 2000 IU/mL but not included in this study. HBV DNA <2000 IU/mL is a level of inactive HBV carriers who are the real candidates for HBsAg loss in hepatitis B envelope antigen–negative patients. It is more important to know the role of this level in the prediction, as well as this level combined with HBsAg <1000 IU/mL.4.“No retreatment” has been well recognized as an important factor of future HBsAg loss, as reviewed elsewhere.7Liaw Y.F. et al.a1.Kaohsiung J Med Sci. 2022; 38: 295-301Crossref Scopus (5) Google Scholar How many of the re-treated patients lost HBsAg during follow-up? It does not seem appropriate to suggest that “patients with both high HBsAg and HBV DNA [what levels?] may be better off restarting anti-viral therapy,” because there are other factors to be considered, such as levels of serum alanine transaminase and bilirubin. In conclusion, the prediction based on HBV DNA and/or HBsAg at 24 weeks of off-therapy follow-up in this study may be interesting but not practical, at least not for TDF-treated patients. In addition, any new predictor needs to be compared with the current best cost-effective predictor for CR and HBsAg loss, which is HBsAg <100 IU/mL. It should also be cautious to recommend restarting treatment, because unnecessary retreatment may deprive the opportunity of HBsAg loss. 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