To the editor, Finite Nuc therapy (FNT) or continued Nuc therapy (CNT), which is better for reducing HCC incidence and improving survival in patients with HBeAg-negative HBVrelated liver cirrhosis? With great interest, we read the article that compared FNT with CNT for HCC incidence/ survival profile by Jeng et al. [1] The authors found that compared with continuous Nuc therapy, FNT could reduce HCC incidence and improve survival in HBeAgnegative HBV-related liver cirrhosis. [1] However, metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), the new confounders discovered with new compelling evidence, [2][3][4][5] should be taken into account in the propensity score matching and multivariate Cox regression analyses to avoid confounding bias.The authors performed some limited multivariate analyses and propensity score matching of age, gender, types of Nuc, platelet count, transaminases, anti-HBV treatment history, and HBsAg levels. [1] However, the analyses of metformin and GLP-1RAs were missing in this cohort study, which was associated with the potential risk of confounding bias regarding the conclusions of HCC incidence and survival profile. Metformin is widely used in diabetics with minimal toxicity, favorable effectiveness, availability, and low cost. GLP-1RAs, a kind of weight-loss drug, topped Science's list of all the breakthroughs in 2023. With the deepening of research, more and more studies have demonstrated that metformin and GLP-1RAs not only play important roles in the management of type 2 diabetes but also shine in the reduction of HCC incidence, survival improvement, and cardiovascular protection. [2][3][4][5] Therefore, metformin and GLP-1RAs are confounders to compare FNT with CNT for HCC incidence/survival profile according to the new evidence. Although positive results were found in the cohort study, [1] there is a possibility that the benefit differences between FNT and CNT were actually caused by the unbalanced distribution of metformin or GLP-1RAs use between the 2 groups. In summary, to obtain the true and convincing benefit differences between the FNT group and the CNT group, it is necessary to supplement the analyses of baseline balance for metformin and GLP-1RAs.
DATA AVAILABILITY STATEMENTThe data that support the findings of this study are all included in this article.