Letter to the Editor: Cautious interpretation of the association between finite treatment and better prognosis in initially HBeAg-negative hepatitis B patients with cirrhosis

To the editor, We read with great interest the article by Jeng et al, which concluded that finite nucleos(t)ide analogue (Nuc) treatment in HBeAg-negative hepatitis B patients with cirrhosis may reduce HCC incidence.1 This is the first study that reported the long-term outcomes after Nuc discontinuation in patients with cirrhosis; however, several crucial aspects require in-depth clarification and further discussion. Firstly, potential selection bias might limit the reliability and generalizability of the results in this retrospective study. The study design and patient recruitment flowchart did not provide detailed screening strategies and enrollment criteria. We speculate that patients in the "finite group" may discontinue Nuc therapy based on the suggestions of clinicians who may choose patients with better clinical characteristics (no family history, mild cirrhosis, etc.). Secondly, we are concerned that the limited long-term benefits reported by this study may mislead the clinical decision to stop Nuc therapy among HBeAg-negative hepatitis B patients with cirrhosis. According to the majority of well-accepted guidelines,2,3 stopping Nuc therapy was not recommended for patients with cirrhosis due to the risk of liver failure. For patients who are HBeAg-negative, although some studies demonstrated that increased HBsAg loss rate can be achieved after discontinuation, the benefit and risk need to be balanced, especially with the wide coverage of Nuc therapy with low cost and good safety profile.4 Of note, 7 patients died of severe hepatitis flare due to Nuc cessation (5 from the "finite group" and 2 from the "continuous group") in this study. Currently, finite therapy is discouraged in patients who are HBeAg-negative unless they achieve HBsAg loss according to the guidelines recommended by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL).2,3 Lastly, the authors did not provide enough evidence to support the theory that low-level HBV viremia is beneficial in reducing HCC incidence by promoting specific immunity against HCC. This theory contradicts the consensus that residual HBV DNA during Nuc therapy is associated with higher HCC risk.5 Hence, the goal of antiviral therapy recommended by all guidelines is to achieve complete viral suppression as soon as possible.2,3