To the Editor:
We read with great interest the recent article in Journal of Hepatology by Yoo et al.
Among 2,520 patients who were alive and recurrence free 2 years after curative resection for HBV-related early-stage (BCLC stage 0/A) hepatocellular carcinoma (HCC), 891 (35.4%) patients developed late recurrence (>2 years after surgery) while 172 (6.8%) achieved HBsAg seroclearance during a median follow-up duration of 6.9 years after resection. Using univariate and multivariate analysis, the authors demonstrated that HBsAg seroclearance was independently associated with a significantly lower risk of late recurrence of HBV-related HCC. As the authors stated at the end of this paper, HBsAg seroclearance has a “beneficial impact” on reducing the risk of late recurrence for patients with HBV-related HCC. Although interesting, we have the following concerns about the inherent relationship between HBsAg seroclearance and late recurrence.
- 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.
J Hepatol. 2022; 77: 939-946
First, in this study, Yoo et al. did not give the details regarding the sequence of HBsAg seroclearance and late recurrence. During the median follow-up of 6.9 years, among 172 patients with HBsAg seroclearance, 36 (20.9%) patients developed late recurrence. It is very possible that some patients first developed late recurrence of HCC and then achieved HBsAg seroclearance in the real world. If so, it is inappropriate for a cohort study to use variables that occurred after the occurrence of the endpoint event. In our opinion, the ambiguous sequentiality between HBsAg seroclearance and late recurrence suggests that the causal relationship between them is really very weak.
Second, by inhibiting viral replication, antiviral therapy has been widely recognized as being associated with reduced postoperative recurrence, especially late recurrence of HBV-related HCC.
- Urata Y.
- Kubo S.
- Takemura S.
- Uenishi T.
- Kodai S.
- Shinkawa H.
- et al.
Effects of antiviral therapy on long-term outcome after liver resection for hepatitis B virus-related hepatocellular carcinoma.
J Hepatobiliary Pancreat Sci. 2012; 19: 685-696
Actually, HBsAg seroclearance is also one of the results of antiviral therapy, although the probability of its occurrence is still very low nowadays.
- Wang M.D.
- Li C.
- Liang L.
- Xing H.
- Sun L.Y.
- Quan B.
- et al.
Early and late recurrence of hepatitis B virus-associated hepatocellular carcinoma.
Oncologist. 2020; 25: e1541-e1551
- Kim G.A.
- Lim Y.S.
- An J.
- Lee D.
- Shim J.H.
- Kim K.M.
- et al.
HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability.
Gut. 2014; 63: 1325-1332
That is to say, both HBsAg seroclearance and the reduction in late recurrence are the consequences of antiviral therapy, and these outcomes co-exist in patients treated with regular antiviral therapy during follow-up.
- Terrault N.A.
- Bzowej N.H.
- Chang K.M.
- Hwang J.P.
- Jonas M.M.
- Murad M.H.
AASLD guidelines for treatment of chronic hepatitis B.
Hepatology. 2016; 63: 261-283
In conclusion, HBsAg seroclearance and no recurrence are optimal outcome events for patients undergoing curative liver resection for HBV-related HCC who receive antiviral therapy during the follow-up period. However, the effect of HBsAg seroclearance on the reduction of recurrence is still worthy of further mechanistic research.
Adjunct Talent Fund of Zhejiang Provincial People's Hospital (No: 2021-YT from Tian Yang).
Study concepts: Yong-Kang Diao, Qing-Yu Kong, Tian Yang; Manuscript preparation and editing: Yong-Kang Diao, Qing-Yu Kong; Manuscript review: Tian Yang. All the authors reviewed the paper and approved the final version. Yong-Kang Diao and Qing-Yu Kong contributed equally to this work.
Conflicts of interest
The authors disclose no conflicts.
Please refer to the accompanying ICMJE disclosure forms for further details.
The following are the supplementary data to this article:
- Multimedia component 1
- Impact of HBsAg seroclearance on late recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection.J Hepatol. 2022; 77: 939-946
- Effects of antiviral therapy on long-term outcome after liver resection for hepatitis B virus-related hepatocellular carcinoma.J Hepatobiliary Pancreat Sci. 2012; 19: 685-696
- Early and late recurrence of hepatitis B virus-associated hepatocellular carcinoma.Oncologist. 2020; 25: e1541-e1551
- HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability.Gut. 2014; 63: 1325-1332
- AASLD guidelines for treatment of chronic hepatitis B.Hepatology. 2016; 63: 261-283
Published online: June 19, 2022
Accepted: June 9, 2022
Received: June 4, 2022
Author names in bold designate shared co-first authorship
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.