Letter: ‘Impact of HCV Eradication on Recurrence Pattern and Long-Term Outcomes in Patients With HCV-Related Hepatocellular Carcinoma Undergoing Radiofrequency Ablation’

Abstract

We read with great interest the recent study by Wu et al. [1]. This study demonstrated that hepatitis C virus (HCV) eradication by antiviral treatment was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following radiofrequency ablation (RFA) in patients with HCV-related HCC. As we all know, sustained virological response (SVR), also known as HCV eradication, is considered to be achieved when HCV RNA becomes undetectable at 24 or 12 weeks post-completion of interferon-based (IFN) or direct-acting antiviral (DAA) treatment. In this study, we found that 63.6% (75/118) of patients achieved SVR after RFA and the status of HCV will change with time, meaning that HCV eradication is a time-dependent variable. The authors excluded instances of early recurrence occurring within 6 months post-initial complete ablation, as well as patients who attained SVR more than 1 year after RFA, from their recurrence analysis, which raises our concerns about the selection of exclusion criteria and statistical methods.

Firstly, over half of the patients who achieved sustained SVR after complete RFA were excluded from the recurrence analysis. The timeframe for achieving HCV eradication is mainly confined to before RFA and within 6–12 months after RFA, significantly restricting the generalisability of the study's findings. Meanwhile, it is possible that some patients first developed recurrence of HCC and then achieved SVR within 6–12 months after RFA in this analysis. It is inappropriate for a cohort study to use variables that occurred after the occurrence of the endpoint event. As previously reported, landmark analysis was more appropriate for this study [2]. Instead of arbitrarily excluding patients who achieved HCV eradication 1 year after RFA, the authors should present the cumulative occurrence curve of patients achieving SVR and then select several significant landmark time points to conduct data analysis. In addition, HCV eradication serves as a time-dependent covariate in this analysis [3]. Consequently, given the violation of the proportional hazards (PH) assumption, the use of the Cox regression model is inappropriate. In our opinion, the time-dependent covariate Cox model is a more suitable choice for evaluating the association between HCV eradication and HCC recurrence [4]. In this model, patients who achieve HCV eradication after RFA during follow-up are switched into the SVR group at the time HCV eradication occurs and remain there until recurrence or death [5, 6].

Although observational studies are important to better understand the effects of drug and seroconversion, their proper design and analysis is essential to avoid major time-related biases [7, 8]. As such, clarification regarding the above mentioned omissions would greatly solidify the conclusions of the study by Wu et al. We also commend the authors for their insightful exploration of HCV-related HCC, which possesses substantial clinical implications.

You-Jian Xu drafted the article. Hui-Ming Pang revised the manuscript and approved the final version.

The authors declare no conflicts of interest.

This article is linked to Wu et al papers. To view these articles, visit https://doi.org/10.1111/apt.18199 and https://doi.org/10.1111/apt.18381.