Review for 10.1186/s12876-021-01606-x (2021)

Reviewer’s report
Title: 
Baseline thrombopoietin level is associated with platelet count
improvement in thrombocytopenic chronic hepatitis C patients after successful
direct-acting antiviral agent therapy
Version: 
0 
Date: 
15 Oct 2020
Reviewer's report:
It's a great pleasure to read this manuscript. This is a single-center, retrospective
study aiming to investigate the role of baseline thrombopoietin (TPO) in platelet
count improvement after successful DAA therapy. The study included 104
patients with chronic hepatitis C. The improvement of platelet count was
analyzed for correlation with the baseline TPO. This study found that platelet
increase from 110k at baseline to 118k twelve weeks after the end of treatment
and baseline TPO level was positively correlated with the improvement. This
might be the first study to focus on the predictive value of baseline TPO for the
improvement of platelet count after DAA therapy. However, I do have a few
concerns. 
Comments: 
Major: 
1. In this study, baseline TPO level predicates platelet count improvement in
chronic hepatitis C patients achieving SVR. But the improvement from 110k to
118k is not clinically significant. Checking the baseline TPO levels in patients
with mild thrombocytopenia will not have a strong impact on clinical practice
and might not be cost-effective. 
2. Patients were only followed for 12 weeks after treatment. Whether there is a
consistent platelet count improvement and whether baseline TPO can predict
long-term platelet count improvement are unclear. 
Minor: 
1. Since patients without SVR were excluded, it might be more accurate to use
the "Baseline thrombopoietin level is associated with platelet count improvement
in thrombocytopenic chronic hepatitis C patients after successful direct-acting
antiviral agent therapy" as the title. 
2. It would be great if authors could explain why using median and range instead
of mean and standard deviation for the continuous variables? As we know, the
median does not use all the information in the data and it can be shown to be less
efficient than the mean; the range doesn't give much indication of the spread of
observation about the mean. (https://www.bmj.com/about-bmj/resources-
readers/publications/statistics-square-one/2-mean-and-standard-deviation)
3. In Table 1, the percentage of patients with significant platelet count
improvement should be 42.3% (44/104), not 41.1%. 
4. Although advanced hepatic fibrosis status, FIB-4, HCC history, splenomegaly,
and ascites were not statistically significant between the two groups in this study,
which might due to a relatively small patient sample size, the group of patients
without significant platelet count improvement did show a tendency of having
more patients with advanced fibrosis and more comorbidities related to that. It
might be worthwhile to point that out. 
5. The rate of fibrosis is 62%, which is high than the rate reported by previous
studies. 
A systematic review of 111 studies analyzing the natural history of HCV
infection estimated that the prevalence of cirrhosis 20 years after infection was
16 percent (95% CI 14-19 percent) (Hepatology. 2008;48(2):418.). This high rate
was likely due to the use of the FIB4 score alone. AASLD mentioned that the
most efficient approach to fibrosis assessment is to combine direct biomarkers
and vibration-controlled transient liver elastography (Fibroscan) (Hepatology
2015 Sep;62(3):932-54.). In future studies, it will be better to include fibroscan
as part of fibrosis assessment. 
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
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