Review for 10.1186/s12876-020-1168-9 (2020)

Reviewer’s report
Title:  High rates of cirrhosis and severe clinical events in patients with HBV/HDV co-infection:
Longitudinal analysis of a German cohort.
Version: 0 Date: 27 Nov 2018
Reviewer: Akihiro Tamori
Reviewer's report:
BMGE-D-18-00611
High rates of cirrhosis and severe clinical events in patients with HBV/HDV co-infection: Longitudinal
analysis of a German real life cohort
Jan-Hendrik Bockmann, MD; Marcel Grube; Vanessa Hamed; Johann von Felden; Johanna Blöcker;
Malte Wehmeyer; Katja Giersch; Michaela Hall; John M. Murray; Maura Dandri; Stefan Lüth; Ansgar
W. Lohse; Marc Lütgehetmann; Julian Schulze zur Wiesch
Authors enrolled 49 patients positive for HBsAg and anti-HDV into the present retrospective study. In
this cohort, clinical events related to liver diseases occurred in 11/49 patients coinfected with HBV and
HDV . Multivariate analysis showed that progression of liver disease at baseline was associated with
overall clinical events, not with serum HDV RNA positivity. 
Coinfection  with  HBV  and  HBV  is  not  common.  So,  the  present  study had  a  potential  unique
information. However, there were several issues to be revised before conclusions. 
First of all, the patients' backgrounds at baseline were different between HBV+HDV coinfection and
HBV  mono-infection.  Comparing  clinical  events  between  two  groups,  authors  should  match  the
backgrounds; age, gender and cirrhosis etc. Propensity score matching method is usually used. 
Second, it is difficult to understand the efficacy of IFN therapy for coinfected patients. Which was the
aim of IFN therapy, HBV or HDV? There was no information about patients' background treated with
IFN, and outcome of HBV markers except HBsAg. 
Next, in case of HCV, anti-HCV positive but HCV RNA negative patient means past HCV infection;
self-limited infection or treatment cure. Among 49 patients, 15 patients showed negative HDV RNA at
baseline and during follow-up. Why such patients were enrolled to the study? 
Minor; 
Three HIV coinfected patients had better be excluded from the study.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If  an  additional  statistical  review  is  recommended,  please  specify  what  aspects  require  further
assessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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