PONE-D-20-09611

Clinical characteristics of paediatric autoimmune hepatitis at a referral hospital in Sub Saharan Africa

PLOS ONE

Dear Dr. Afaa,

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Nikhil Pai, BSc, MD

Academic Editor

PLOS ONE

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Additional Editor Comments:

Thank you for your submission and your patience with this decision. I would look forward to seeing the comments from the authors thoughtfully addressed and resubmitted. In recognition of the paucity of data from Sub Saharan Africa on this topic, I would encourage the authors to please refine this manuscript further for re-review. Once sent back, we will consider the submission further in light of the requisite edits and issue a further decision.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: N/A

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for writing up your experience with paediatric AIH. There is not much data from Africa and your efforts are applauded. Nonetheless there are some comments that need to be addressed.

Major comments:

- There were a few patients who were ANA negative and ASMA negative with high IgG levels. Indeed IgG levels become elevated in cirrhosis (of any cause). How did the authors confirm a diagnosis of AIH in these children?

- A frequent differential diagnosis for AIH is drug induced liver injury - The authors need to make a comment of whether these patients were taking any medications including herbs/over the counter meds which may have caused DILI

- Could the authors do a Simplified AIH score for their patients? (Hennes et al. Hepatology 2008 Jul;48(1):169-76. doi: 10.1002/hep.22322.).

Can be done at: https://www.mdcalc.com/simplified-autoimmune-hepatitis-aih-score

- The authors mentioned that AIH patients typically present with elevated transaminases. Yet the ALT and AST levels are not presented as well as the other liver function tests (bilirubin, ALP, GGT, albumin) are not presented in the results. Do the authors have this information?

- It is difficult to determine from the results what proportion of patients had a response. This is touched upon in the discussion but really belongs in the results.Typically in Type 1 AIH, 75% of patients are steroid responsive. Also how was the prednisolone weaned over time? What was the maintenance therapy? did patients stay on AZA alone and were weaned off pred? or did they stay on low dose pred? A little more details is needed here

- How long was the median follow-up period for these patients?

- It would be interesting to know if these patients had previously engaged in the hospital (for other reasons) and AIH could have been screened for earlier?

- Did the authors have any information on family history?

- I suggest the authors have subheadings to present the results section rather than 1 whole paragraph.

I.e. Demographics, Clinical and laboratory features, treatment, Outcome

- the section about cause of the 2 deaths belongs in the results section, not the discussion

- The authors should mention briefly about the limitations of the study - e.g. small patient numbers, lack of long follow-up, etc.

Minor comments:

- the acronym SSA for sub Saharan Africa is used without being previously defined in the abstract

- please be consistent with British vs. American spelling. The authors use words like “aetiology” and “paediatric” which is British spelling and then “Normalization” and “titer” which is American spelling.

- the sentence “thirteen patients aged between 5 years to 13 years…” in the Methods should be removed as it belongs in the Results section.

- similarly “Treatment was with steroid with or without azathioprine…” should be removed from the Data collection section”.

- I would change the terms “autoimmune sclerosis cholangitis” and “sclerosing cholangitis” to “primary sclerosing cholangitis”

Reviewer #2: In their retrospective case series “Clinical characteristics of paediatric autoimmune hepatitis at a referral hospital in Sub Saharan Africa» Afaa et al. describe the clinical characteristics of 13 patients.

The introduction

is a general review of AIH, which should be shortened. Instead, I would suggest expanding on clinical features in pediatric AIH described in developed and developing countries (Africa and other parts of the world) in order to lead to a reason why their experience with AIH should be added to the literature.

Results

Did the patient had already cirrhosis? Which stage?

How long was the follow-up time?

Two patient died, please expand on their disease course in the result section. Why did the die?

In table 1

It is stated that 11 patients had AIH and 2 sclerosing cholangitis. Did the later 2 had overlap disease? In the text it is stated that all patients had AIH – please specifiy.

For the expression “hepatic failure” I would suggest using the King’s College criteria for definition of Acute Liver Failure and additionally report the INR value at presentation for all patients.

It would be interesting to document the lab values at presentation. Could the authors provide numbers for liver enzymes (ASAT, ALAT), gGT, albumin, thrombocytes, bilirubin.

For table 2

could the authors state, whether the measured antibodies were negative or not available/ not performed and provide numbers for IgG or at least the multiple of the upper limit of normal.

Please add a legend to the table with the full names of the antibodies, etc.

Discussion

“The positive report of both the hepatitis C virus and Schistosomiasis antibodies are due to the general over production of immunoglobulins in patients with AIH”. – please add a reference for this statement.

In table 2 there are 3 patients with schistosomiasis IgM, in the discussion are only two mentioned, please correct/specify. Why were the patients “treated with 2 courses of praziquantel” when the authors assume that the overproduction of immunoglobulins are responsible for the IgM? – please discuss.

“The finding of 15.4% of these cohorts with normal Ig G level” – as the patients number is low, I would suggest to also state numbers e.g. “Two (15%) patients had normal IgG levels”

Interestingly there are ¾ of patients with insidious onset. In general it is documented to be less than 40% – please discuss.

What is the message of the findings from these 13 patients? The conclusion the authors give is common knowledge.

Some English editing needed.

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Reviewer #1: No

Reviewer #2: No

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Clinical characteristics of paediatric autoimmune hepatitis at a referral hospital in Sub Saharan Africa

PONE-D-20-09611R1

Dear Dr. Afaa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Nikhil Pai, BSc, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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