Hepatocellular carcinoma (HCC) is the most common malignant tumor in the elderly, and the highest age-specific rates of HCC are observed among persons over age 70 years in developed countries[14]. The mean age of HCC patients at first diagnosis is increasing[15], possibly due to the aging of the population, increase in life expectancy, improvement in overall health conditions, as well as the use of antiviral therapy in high prevalence regions, which may delay the occurrence of HCC[16, 17].
HBV infection is regarded as an important risk factor for tumor recurrence and is associated with poor prognosis in HCC patients[7, 18, 19]. In contrast, some clinical studies found no significant correlation between the HBV DNA levels or HBeAg status and the development of HBV-related HCC[20, 21]. Basic studies showed that HBV DNA level was lower in old people[11] and Spontaneous HBsAg seroclearance was higher in patients older than 60 years[12]. A study in paradigms for HBV-related human carcinogenesis found that epigenetic pathways (transactivation, insertional mutagenesis, chromosomic arrangements) were more obvious in the elderly[22]. In addition, there are other non-viral causes of HCC in the elderly. Old age seems to favor non-alcoholic fatty liver disease (NAFLD), NASH, and ultimately HCC [23]. Therefore, the role of HBV infection is unclear in HBV-related HCC recurrence for the elderly.
Several studies showed that postoperative adjutant AVT benefits HBV-related HCC patients by decreasing tumor recurrence[6–8]. However, patients were from a single department, the sample size was limited in the RCT, and the including patients were not widely representative in these studies. In contrast, other studies showed that there was no significant effect of postoperative AVT on HBV-related HCC recurrence. The study of Li N et al. found no significant effect of postoperative AVT on HBV-related HCC recurrence in the two groups (76.7 vs. 91.7%; P = 0.077) after the follow-up period[9]. Another study by Kuzuya et al reported that the 1- and 2-year disease-free survival rates were 23.3 and 2.3%, respectively, for the treatment group, and 8.3% and 0%, respectively, for the control group (P = 0.072)[10]. To the best of our knowledge, there are no relevant studies on anti-HBV therapy to prevent postoperative recurrence of HBV-related HCC in the elderly. Based on our respective cohort study, we found that postoperative adjuvant AVT was not significantly associated with a decrease in tumor recurrence after curative hepatic resection for HBV-related elderly HCC patients, which was consistently observed in propensity score matching. Moreover, multivariate Cox analysis also revealed that postoperative adjuvant AVT was not an independent protected factor associated with tumor recurrence after curative hepatic resection for HBV-related elderly HCC patients.
In theory, AVT may affect long-term survival by directly modulating the remnant liver function which improves the patient’s tolerance to various treatments for tumor recurrence[10, 24]. In our study, we found that postoperative adjuvant AVT was statistically significantly associated with an increase in long-term survival after curative hepatic resection for HBV-related elderly HCC patients, which was consistently observed in propensity score matching. And, multivariate Cox analysis also revealed that postoperative adjuvant AVT was an independent protected factor associated with long-term survival after curative hepatic resection for HBV-related elderly HCC patients. These results are agreed with previous studies[6, 9, 25].
There are some limitations in our study. First, part of the patients who were treated in the early period of this study failed to receive AVT, though they might meet the treatment criteria of AVT. Second, this study was a retrospective study, which may be subject to bias and confounding. To overcome this issue, we conducted propensity score matching to minimize the differences. We also did not investigate the type of AVT due to the variety in medications and the limited sample size of patients who received a distinct drug, all of which made effective statistical analysis difficult. Third, in this study, it was difficult to evaluate the effect of the HBV genotype, which is likely to affect HCC incidence and NA efficacy.
In conclusion, among patients who underwent curative hepatic resection for HBV-related elderly HCC. Postoperative adjuvant AVT can improve long-term survival, but was not the independent protective factor associated with tumor recurrence. At present, there is no standard adjuvant treatment for the prevention of HCC recurrence in patients who undergo hepatic resection. Given the benefits of improving long-term survival, improving remnant liver function, and affordable and convenient treatment. We still recommended that HBV-related elderly HCC patients receive adjuvant AVT after curative hepatic resection.