Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a HBV infected patient

The reporting of a sequence analysis of complete genome of subgenotype C2 of hepatitis B virus is new in Bangladesh perspective. The article as ‘research note’ is quite acceptable.

But, regarding the ‘chronic status’ of patient, it may be changed at all portion of the article except in ‘results and discussion’ part where it may be kept as a possibility of being chronic (because ‘history of minor surgery few years back and brother was positive for HBV years ago’). The chronic status of the patient was not established by serological evidence (e.g. HBsAg positivity 6 months back).The change of ‘chronic’ status  starts from title- where ‘from a patient with uncomplicated chronicity’ may be changed to ‘HBV infected patient’

In the abstract, ‘a patient with chronic HBV infection’ may be changed to ‘HBV infected patient’ and from ‘to identify potential therapies against chronic HBV infections’ ‘chronic’ word may be omitted.

In the introduction part- ‘Most of the HBV cases are chronic, …. hepatocellular carcinoma’ is misleading.  It needs rewriting as ‘Most chronic HBV cases have a high possibility causing liver cirrhosis and hepatocellular carcinoma’. In last line, ‘from a patient with chronic HBV infection carrying the virus for a long time’ may be replaced by ‘from a patient having HBV infection’.

In the methods part-  ‘The infected patient……..determined by USG. The Patient was diagnosed with chronic HBV infection, suggested by presence of the presence of ascitis…..high viral load in the plasma.’ These two lines need rewriting, mentioning the possibility of being chronic. But, again lack of serological evidence needs to be mentioned.

This paper reports a sequence analysis of a strain of hepatitis B virus. However, there are some aspects of the paper that merit attention. In the Abstract and again in the Introduction the authors state: The number of chronic cases of hepatitis B virus (HBV) is increasing rapidly in the world".  I found this an interesting statement and wondered what was the evidence base for this. In the Introduction the authors cite MacLachlan and Cowie (2015). It appears to me that the authors are mis-quoting this reference. The reference actually says "The burden of chronic HBV infection is increasingly being recognized", this is substantially different from suggesting that the number of cases is increasing. There is a general lack of comprehensive epidemiological information on chronic hepatitis B infection as many developing countries (the epicentre of chronic HBV infections) lack surveillance to provide data. We do not know how WHO programmes to prevent vertical transmission of HBV are impacting on chronic hepatitis B and I believe we lack information to support the assertion of a global increase in numbers.

Also in the abstract - the third line ""with current common amino acid substitutions"  is not a meaninglful statement. The sentence needs rewriting to make clear what the authors actually mean.

Introduction 1st paragraph
last 2 lines: "which makes it relatively higher risk than other infectious diseases" ; it is unclear what is meant here, a rate of 2-6% is clearly low compared with risk of, for example, influenza or rotavirus infection.

Introduction, 2nd Paragraph "the mutation rate of hepatitis B is high"  and " hence, recombinant strains are evolving with a common pattern". Mutation is a random event how can a random event lead to a commonly evolving pattern. The authors need to recast the sentence to explain what they really mean.

Introduction, end of 2nd paragraph. the genome was isolated from "a patient without liver complication" yet in methods we are told the patient has chronic liver disease as adjudged by ultrasonography.

Methods: line 4. Was formal staging not used to describe liver disease e.g. relating shear wave elastography to fibrosis score? Were liver function tests performed?

Methods, line 5 "The patient was diagnosed with chronic hepatitis B recently". This seems strange, the standard definition of chronic hepatitis B infection is the detection of hepatitis B surface antigen in serum for more than 6 months. This patient - with blood taken only one month post diagnosis would not seem to meet the definition. No hepatitis B markers results  are given for the patient and so understanding of the phase of chronic illness (see EASL guidance;Journal of Hepatology 2017 vol. 67: 370–398) is not possible

Analysis - reference needed for the HBV Geno2Pheno software used.

What evidence is there that the HBV/C2 isolate sequenced is a common phenotype in chronic hepatitis B virus infection in Bangladesh? Without such evidence it is difficult to see how the conclusions "The findings of this study will help...." are justified. This could simply be an single instance of this virus produced through random mutation.It is therefore also difficult to understand how this could be considered a 'reference strain' for chronic hepatitis B as it may represent a single instance and further as the patient does not appear to meet a case definition of having chronic hepatitis B infection, can it be considered as a reference strain for chronic hepatitis B infection.