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HBsAg seroclearance reduces the risk of late recurrence in HBV-related HCC

  • Bao Jin
    Affiliations
    Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
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  • Shunda Du
    Affiliations
    Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
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  • Huayu Yang
    Correspondence
    Corresponding author. Address: Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
    Affiliations
    Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
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      Linked Article

      To the Editor:
      We read with great interest the article published in the Journal of Hepatology by Yoo et al. and colleagues.
      • Yoo S.
      • Kim J.Y.
      • Lim Y.S.
      • Han S.
      • Choi J.
      Impact of HBsAg seroclearance on late recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection.
      This study found that HBsAg loss was associated with a 38% lower risk of late recurrence of hepatocellular carcinoma (HCC) after curative liver resection compared with persistent HBsAg positivity. We appreciate their efforts to provide new insights into the postoperative recurrence of HBV-related HCC. However, we believe that there are some issues that merit further discussion to ensure that the results of this study are more convincing.
      First, there were significant differences in many baseline characteristics between the HBsAg-positive group and HBsAg serocleared group in this study, which may affect the interpretation of results. Although the authors used propensity scores and time-dependent covariate Cox models, which are general statistical analysis methods for reducing bias,
      • Chen Z.H.
      • Zhang X.P.
      • Feng S.
      • Feng J.K.
      • Chai Z.T.
      • Guo W.X.
      • et al.
      Liver resection versus intensity-modulated radiation therapy for treatment of hepatocellular carcinoma with hepatic vein tumor thrombus: a propensity score matching analysis.
      ,
      • Jeong S.
      • Luo G.
      • Gao Q.
      • Chen J.
      • Liu X.
      • Dong L.
      • et al.
      A combined Cox and logistic model provides accurate predictive performance in estimation of time-dependent probabilities for recurrence of intrahepatic cholangiocarcinoma after resection.
      potential bias and residual confounders cannot be completely eliminated. The authors used the absolute standardized difference (ASD) to compare the differences in baseline characteristics between the 2 groups, and the difference was generally considered small when ASD <0.10. In the HBsAg seroclearance group in this study, patients had lower aspartate aminotransferase, alanine aminotransferase, and HBV DNA levels, less satellite nodules, and a lower proportion had cirrhosis, as shown in Table 1.
      • Yoo S.
      • Kim J.Y.
      • Lim Y.S.
      • Han S.
      • Choi J.
      Impact of HBsAg seroclearance on late recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection.
      Studies have shown that high viral load and hepatic inflammatory activity are associated with an increased risk of late recurrence of HBV-related HCC.
      • Wu J.C.
      • Huang Y.H.
      • Chau G.Y.
      • Su C.W.
      • Lai C.R.
      • Lee P.C.
      • et al.
      Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma.
      ,
      • Muller X.
      • Mohkam K.
      • Mabrut J.Y.
      Inflammation is king in liver resection for hepatocellular carcinoma.
      Yao et al. reported that satellite nodules are also an independent risk factor for postoperative recurrence of HCC.
      • Yao L.Q.
      • Chen Z.L.
      • Feng Z.H.
      • Diao Y.K.
      • Li C.
      • Sun H.Y.
      • et al.
      Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: a multi-institutional analysis.
      The authors should use more stringent propensity score matching and other statistical methods to minimize the differences in baseline characteristics between the 2 groups.
      Second, the authors did not report some other factors that may affect the recurrence of HCC in the 2 groups of patients, including preoperative alpha-fetoprotein level, surgical margin, intraoperative blood transfusion, and postoperative adjuvant therapy.
      • Yao L.Q.
      • Chen Z.L.
      • Feng Z.H.
      • Diao Y.K.
      • Li C.
      • Sun H.Y.
      • et al.
      Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: a multi-institutional analysis.
      Transarterial chemoembolization (TACE) is often recommended as an adjuvant therapy after surgery for patients with early-stage HCC combined with high-risk recurrence factors, such as multiple tumors and microvascular invasion. Studies have shown that TACE can reduce the risk of recurrence in patients with liver cancer after radical surgery.
      • Lu J.
      • Zhao M.
      • Arai Y.
      • Zhong B.Y.
      • Zhu H.D.
      • Qi X.L.
      • et al.
      Clinical practice of transarterial chemoembolization for hepatocellular carcinoma: consensus statement from an international expert panel of International Society of Multidisciplinary Interventional Oncology (ISMIO).
      ,
      • Zhou J.
      • Sun H.
      • Wang Z.
      • Cong W.
      • Wang J.
      • Zeng M.
      • et al.
      Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 Edition).
      The findings of this study could be further strengthened if the authors could additionally provide details on these factors. In addition, patients were included in this study from 2000 to 2017, which is a very long time. Over time, advances in surgical techniques, including the concept of tumor-free resection and less invasive surgical procedures, may affect the recurrence of liver cancer. Subgroup analyses of different time periods may help to eliminate the potential effect of the long study period.
      In conclusion, we agree with the main conclusion of the study and applaud the authors for this important study. This study found that, in patients with early-stage HBV-related HCC undergoing radical liver resection, HBsAg seroclearance was associated with a reduced risk of late recurrence. However, baseline differences must be excluded and more factors affecting recurrence must be reported to obtain more reliable conclusions.

      Financial support

      The authors received no financial support to prepare this manuscript.

      Authors' contributions

      B.J. and H.Y. conceived the manuscript. All authors wrote and reviewed the manuscript.

      Conflict of interest

      The authors disclose no conflict of interest.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following are the supplementary data to this article:

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        Impact of HBsAg seroclearance on late recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection.
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