Letter to the Editor: Is the evidence convincing for the expansion of CHB treatment criteria to reduce the risk of HCC?

To the editor, Finding and removing the risk factors is one of the optimal strategies for the global prevention of HCC. With great enthusiasm, we read the significant cohort study1 by Huang et al published in Hepatology, in which a 70% reduction of HCC risk due to antiviral therapy was found among patients with indeterminate-phase chronic hepatitis B (CHB). The present results are an indispensable supplement for the relevant guideline in the expansion of the CHB treatment criteria to reduce the risk of HCC.1 If some key data could be further disclosed and analyzed, the strength of the evidence in this paper will be upgraded. The authors performed an inverse probability of treatment weighting analysis to balance baseline characteristics between the comparative groups in the Results section to reduce the risk of biases.1 The involved parameters for inverse probability of treatment weighting analyses included the presence of diabetes, alcohol, body mass index, and so on.1 However, some proven confounders were missing in the inverse probability of treatment weighting analyses, including some uncaptured risk factors and some uncaptured protective factors in Figure 1.2–5 The same flaws exist in the univariable and multivariable Cox proportional hazards regression analyses.1 As shown in Figure 1, the missing confounding factors of anti-HBV treatment (uncaptured risk/protective factors for HCC) include HDV and anti-HDV treatment, the use of glucagon-like peptide-1 receptor agonists for obesity, fatty liver disease and anti-fatty liver disease interventions, cardiovascular disease and use of statins, and smoking and well lifestyle interventions for smoking.2–5 The missing analyses of these uncaptured confounders are potential sources of biases. Therefore, supplementary analyses according to these uncaptured parameters should be performed to fully confirm the causality and its strength between anti-HBV treatment and the risk of HCC among patients with indeterminate-phase CHB.FIGURE 1: The multidimensional relationships among the risk factors/pathogeny, the protective factors/intervention, and the risk of HCC. Abbreviation: GLP-1, glucagon-like peptide-1.This multinational study1 by Huang et al is a necessary supplement for the future revision of relevant practice guidelines regarding antiviral treatment indications for patients with CHB. Therefore, we encourage the authors to make more efforts for the aforementioned data acquisition, sharing, and analysis, which is required to upgrade the strength of the evidence for the future revision of CHB guidelines.