Title: Efficacy of extracorporeal immunoadsorption therapy for removal of HBsAg
Version: 2 Date: 22 Mar 2025
Reviewer's report:
The article entitled “Efficacy of extracorporeal immunoadsorption therapy for removal of
HBsAg” is self-explanatory." This is an observational study in which HBsAg clearance was the
target of the study. In short, the authors prepared agarose beads containing antibodies to hepatitis
B surface antigen (HBsAg) [anti-HBs]. The characterization of these beads moved on. These
anti-HBs-containing beads had potent capacity to neutralize HBsAg in vitro. Finally, the study
enrolled to show its capacity in an animal model. Use of anti-HBs coated beads was able to
reduce HBsAg and HBV DNA in rabbits.  Based on these observations, the authors commented
that this approach may act as a therapeutic option for the functional cure of chronic hepatitis
B virus (HBV)-infected patients. The article has been reviewed before appearing to me. I am
going to omit repeated comments and focus on the fundamental defects of the article.
Comments
1. The entire study is a defaulted one concerning the fundamental problem of management of
chronic hepatitis B (CHB) patients. It is true that HBsAg reduction by commercially available
drugs is not up to the mark, and this represents a major problem in this regard. Any effort to clear
or reduce HBsAg in CHB patients would be a notable contribution in this context. However,
HBsAg reduction must be associated with containment of the replicative process of HBV in the
CHB patients. In any kind of study where HBsAg is neutralized by this type of approach, it is
either a problem to realize the pathogenesis of CHB progression or just a non-scientific view
over the matter in a holistic manner. After treating CHB patients with antiviral drugs, HBsAg
reduction is expected as a part of the antiviral and immune modulatory action of this drug.
Reduction of HBsAg by anti-HBs beads in a transient manner is not something that is warranted
in CHB patients. Accordingly, it is natural to ask how long HBsAg reduction prevailed in this
animal model.
2. The next issue is regarding the animal model of HBV. The authors injected HBsAg to produce
an animal model of CHB or HBV carrier state. This is a childish approach, and it is never
an accepted mode. Several models of HBV carrier states of CHB have been produced in the
world since 1985. But this type of approach is a confusing one. I would request the authors to
authenticate their model in Rabbit.
3. When an animal model of HBV carrier state is implemented by injecting HBsAg, how may
the rabbit express HBV DNA?  I am really confused regarding the total motive of the authors
and how they proceeded on with this study.
4. HBV DNA was depleted about 66% from rabbit blood. How did the rabbit get HBV DNA?
This requires a clear explanation.
5. As the fundamental basis of the study is in question, the model is not accepted and seems to
be elusive; the result and discussion seem irreverent.
Title: Efficacy of extracorporeal immunoadsorption therapy for removal of HBsAg
Version: 2 Date: 22 Mar 2025
Reviewer's report:
The article entitled “Efficacy of extracorporeal immunoadsorption therapy for removal of
HBsAg” is self-explanatory." This is an observational study in which HBsAg clearance was the
target of the study. In short, the authors prepared agarose beads containing antibodies to hepatitis
B surface antigen (HBsAg) [anti-HBs]. The characterization of these beads moved on. These
anti-HBs-containing beads had potent capacity to neutralize HBsAg in vitro. Finally, the study
enrolled to show its capacity in an animal model. Use of anti-HBs coated beads was able to
reduce HBsAg and HBV DNA in rabbits.  Based on these observations, the authors commented
that this approach may act as a therapeutic option for the functional cure of chronic hepatitis
B virus (HBV)-infected patients. The article has been reviewed before appearing to me. I am
going to omit repeated comments and focus on the fundamental defects of the article.
Comments
1. The entire study is a defaulted one concerning the fundamental problem of management of
chronic hepatitis B (CHB) patients. It is true that HBsAg reduction by commercially available
drugs is not up to the mark, and this represents a major problem in this regard. Any effort to clear
or reduce HBsAg in CHB patients would be a notable contribution in this context. However,
HBsAg reduction must be associated with containment of the replicative process of HBV in the
CHB patients. In any kind of study where HBsAg is neutralized by this type of approach, it is
either a problem to realize the pathogenesis of CHB progression or just a non-scientific view
over the matter in a holistic manner. After treating CHB patients with antiviral drugs, HBsAg
reduction is expected as a part of the antiviral and immune modulatory action of this drug.
Reduction of HBsAg by anti-HBs beads in a transient manner is not something that is warranted
in CHB patients. Accordingly, it is natural to ask how long HBsAg reduction prevailed in this
animal model.
2. The next issue is regarding the animal model of HBV. The authors injected HBsAg to produce
an animal model of CHB or HBV carrier state. This is a childish approach, and it is never
an accepted mode. Several models of HBV carrier states of CHB have been produced in the
world since 1985. But this type of approach is a confusing one. I would request the authors to
authenticate their model in Rabbit.
3. When an animal model of HBV carrier state is implemented by injecting HBsAg, how may
the rabbit express HBV DNA?  I am really confused regarding the total motive of the authors
and how they proceeded on with this study.
4. HBV DNA was depleted about 66% from rabbit blood. How did the rabbit get HBV DNA?
This requires a clear explanation.
5. As the fundamental basis of the study is in question, the model is not accepted and seems to
be elusive; the result and discussion seem irreverent.
Please review this paper.
user
Title: Efficacy of extracorporeal immunoadsorption therapy for removal of HBsAg
Version: 2 Date: 22 Mar 2025
Reviewer's report:
The article entitled “Efficacy of extracorporeal immunoadsorption therapy for removal of
HBsAg” is self-explanatory." This is an observational study in which HBsAg clearance was the
target of the study. In short, the authors prepared agarose beads containing antibodies to hepatitis
B surface antigen (HBsAg) [anti-HBs]. The characterization of these beads moved on. These
anti-HBs-containing beads had potent capacity to neutralize HBsAg in vitro. Finally, the study
enrolled to show its capacity in an animal model. Use of anti-HBs coated beads was able to
reduce HBsAg and HBV DNA in rabbits.  Based on these observations, the authors commented
that this approach may act as a therapeutic option for the functional cure of chronic hepatitis
B virus (HBV)-infected patients. The article has been reviewed before appearing to me. I am
going to omit repeated comments and focus on the fundamental defects of the article.
Comments
1. The entire study is a defaulted one concerning the fundamental problem of management of
chronic hepatitis B (CHB) patients. It is true that HBsAg reduction by commercially available
drugs is not up to the mark, and this represents a major problem in this regard. Any effort to clear
or reduce HBsAg in CHB patients would be a notable contribution in this context. However,
HBsAg reduction must be associated with containment of the replicative process of HBV in the
CHB patients. In any kind of study where HBsAg is neutralized by this type of approach, it is
either a problem to realize the pathogenesis of CHB progression or just a non-scientific view
over the matter in a holistic manner. After treating CHB patients with antiviral drugs, HBsAg
reduction is expected as a part of the antiviral and immune modulatory action of this drug.
Reduction of HBsAg by anti-HBs beads in a transient manner is not something that is warranted
in CHB patients. Accordingly, it is natural to ask how long HBsAg reduction prevailed in this
animal model.
2. The next issue is regarding the animal model of HBV. The authors injected HBsAg to produce
an animal model of CHB or HBV carrier state. This is a childish approach, and it is never
an accepted mode. Several models of HBV carrier states of CHB have been produced in the
world since 1985. But this type of approach is a confusing one. I would request the authors to
authenticate their model in Rabbit.
3. When an animal model of HBV carrier state is implemented by injecting HBsAg, how may
the rabbit express HBV DNA?  I am really confused regarding the total motive of the authors
and how they proceeded on with this study.
4. HBV DNA was depleted about 66% from rabbit blood. How did the rabbit get HBV DNA?
This requires a clear explanation.
5. As the fundamental basis of the study is in question, the model is not accepted and seems to
be elusive; the result and discussion seem irreverent.
assistant