Reviewer's report 
 Complete Hepatitis B Virus genome analysis in HBsAg positive mothers and their infants with Title: 
fulminant hepatitis B 
 1  8 April 2004 Version: Date: 
 Cyrille FÃ©ray Reviewer: 
Reviewer's report: 
This paper analyzed the very interesting issue of the vertical transmission of HBV. The studied 
cases are extremely interesting since all 5 children had fulminant hepatitis. Unfortunately, the authors analyzed these very precious cases through direct sequencing of HBV DNA. Although the complete genome was studied, this approach does not permit a complete interpretation of the 
results. Indeed, direct sequencing gives the consensus sequence and not the sequences of 
individual virions. It is thus not possible to perform any phylogenetic studies and to precisely follow the selective pressure occurring on different quasispecies during the course of fulminant hepatitis. 
However, in spite of this major drawback, this paper provides some interesting findings such as hot 
spot mutations in regulatory or immunodominant regions and also the fact that all cases were genotype D . On a general point of view, a major explanation for all these findings is that the variant detected in children likely during FH were the more fitted to the complexe course and setting of 
fulminant hepatitis B. In this view, the viral load although tested have been omitted in the results. The 
strains which are analyzable at this late stage of the disease are not obligatory those which were 
present at the onset of disease. This hypothesis is cited by the authors at the end of the paper but must be emphasized. The fact that HBV strains were not available before the onset of liver disease 
must be underlined. 
The following points must be precised: 
- The limitations of the approach (direct sequencing) must be precised. 
- Did these babies have low viremia as classical during fulminant hepatitis ? 
- What was children’s liver function at the time of study ? 
- Were the mother sampled at the time of birth or when their children were sick ? 
- What was the viral load of chidren and their HBe status ? 
1. Is the question posed by the authors new and well defined? 
yes 
2. Are the methods appropriate and well described, and are sufficient details provided to replicate 
the work? 
no 
3. Are the data sound and well controlled? 
yes 
4. Does the manuscript adhere to the relevant standards for reporting and data deposition? 
yes 
5. Are the discussion and conclusions well balanced and adequately supported by the data? 
yes 
6. Do the title and abstract accurately convey what has been found? 
yes 
7. Is the writing acceptable? 
yes 
Reviewer's report 
 Complete Hepatitis B Virus genome analysis in HBsAg positive mothers and their infants with Title: 
fulminant hepatitis B 
 1  8 April 2004 Version: Date: 
 Cyrille FÃ©ray Reviewer: 
Reviewer's report: 
This paper analyzed the very interesting issue of the vertical transmission of HBV. The studied 
cases are extremely interesting since all 5 children had fulminant hepatitis. Unfortunately, the authors analyzed these very precious cases through direct sequencing of HBV DNA. Although the complete genome was studied, this approach does not permit a complete interpretation of the 
results. Indeed, direct sequencing gives the consensus sequence and not the sequences of 
individual virions. It is thus not possible to perform any phylogenetic studies and to precisely follow the selective pressure occurring on different quasispecies during the course of fulminant hepatitis. 
However, in spite of this major drawback, this paper provides some interesting findings such as hot 
spot mutations in regulatory or immunodominant regions and also the fact that all cases were genotype D . On a general point of view, a major explanation for all these findings is that the variant detected in children likely during FH were the more fitted to the complexe course and setting of 
fulminant hepatitis B. In this view, the viral load although tested have been omitted in the results. The 
strains which are analyzable at this late stage of the disease are not obligatory those which were 
present at the onset of disease. This hypothesis is cited by the authors at the end of the paper but must be emphasized. The fact that HBV strains were not available before the onset of liver disease 
must be underlined. 
The following points must be precised: 
- The limitations of the approach (direct sequencing) must be precised. 
- Did these babies have low viremia as classical during fulminant hepatitis ? 
- What was children’s liver function at the time of study ? 
- Were the mother sampled at the time of birth or when their children were sick ? 
- What was the viral load of chidren and their HBe status ? 
1. Is the question posed by the authors new and well defined? 
yes 
2. Are the methods appropriate and well described, and are sufficient details provided to replicate 
the work? 
no 
3. Are the data sound and well controlled? 
yes 
4. Does the manuscript adhere to the relevant standards for reporting and data deposition? 
yes 
5. Are the discussion and conclusions well balanced and adequately supported by the data? 
yes 
6. Do the title and abstract accurately convey what has been found? 
yes 
7. Is the writing acceptable? 
yes 
Please review this paper.
user
Reviewer's report 
 Complete Hepatitis B Virus genome analysis in HBsAg positive mothers and their infants with Title: 
fulminant hepatitis B 
 1  8 April 2004 Version: Date: 
 Cyrille FÃ©ray Reviewer: 
Reviewer's report: 
This paper analyzed the very interesting issue of the vertical transmission of HBV. The studied 
cases are extremely interesting since all 5 children had fulminant hepatitis. Unfortunately, the authors analyzed these very precious cases through direct sequencing of HBV DNA. Although the complete genome was studied, this approach does not permit a complete interpretation of the 
results. Indeed, direct sequencing gives the consensus sequence and not the sequences of 
individual virions. It is thus not possible to perform any phylogenetic studies and to precisely follow the selective pressure occurring on different quasispecies during the course of fulminant hepatitis. 
However, in spite of this major drawback, this paper provides some interesting findings such as hot 
spot mutations in regulatory or immunodominant regions and also the fact that all cases were genotype D . On a general point of view, a major explanation for all these findings is that the variant detected in children likely during FH were the more fitted to the complexe course and setting of 
fulminant hepatitis B. In this view, the viral load although tested have been omitted in the results. The 
strains which are analyzable at this late stage of the disease are not obligatory those which were 
present at the onset of disease. This hypothesis is cited by the authors at the end of the paper but must be emphasized. The fact that HBV strains were not available before the onset of liver disease 
must be underlined. 
The following points must be precised: 
- The limitations of the approach (direct sequencing) must be precised. 
- Did these babies have low viremia as classical during fulminant hepatitis ? 
- What was children’s liver function at the time of study ? 
- Were the mother sampled at the time of birth or when their children were sick ? 
- What was the viral load of chidren and their HBe status ? 
1. Is the question posed by the authors new and well defined? 
yes 
2. Are the methods appropriate and well described, and are sufficient details provided to replicate 
the work? 
no 
3. Are the data sound and well controlled? 
yes 
4. Does the manuscript adhere to the relevant standards for reporting and data deposition? 
yes 
5. Are the discussion and conclusions well balanced and adequately supported by the data? 
yes 
6. Do the title and abstract accurately convey what has been found? 
yes 
7. Is the writing acceptable? 
yes 
assistant