Title: Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B
virus-related acute-on-chronic liver failure in males
Version: 1 Date: 20 Mar 2021
Reviewer's report:
This is an interesting and well written paper regarding the impact of testosterone in male patients
with hepatitis B virus related acute on chronic liver failure (HBV-ACLF). The authors evaluated
160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB)
and 106 healthy controls (HC) and they found that low serum levels of total testosterone were
associated with increased stage of ascites, hepatic encephalopathy, MELD and HBVB-ACLF
scores, while low testosterone (<142.39 ng/dL) was a risk factor for both the composite outcome
and for death alone within 90 days.
However, there are some issues which should be addressed by the authors
1) SHBG needs abbreviation
2) Declaration of Helsinki needs update
3) The authors stated that the patients underwent artificial liver support system. Can they clarify
better this issue? For how long did they receive this support? How this support can affect their
results?
4) Did the authors have any data regarding the causes of ACLF? Infection, G.I. bleeding etc
5) “MELD and COSSH ACLF were calculated using the most abnormal value”. Is it true? Na
d not at baseline similar to hormones evaluation?
6) MELD score was MELD-Na or original?
7) SPSS version needs update
8) Page 10: SHBG is not a hormone
9) Any data regarding antiviral therapy?
10) Table 1: How did the authors explain that cortisol was lower in early stage that middle and
end-stage of HBV-ACLF? Similar comment for DHEAS
11) Table 3: Estimate? 95%CI?
12) Total testosterone should be excluded from Table 4
13)  In cox regression analysis for the outcome all the variables significantly associated with the
outcome in univariate analysis should be included
Title: Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B
virus-related acute-on-chronic liver failure in males
Version: 1 Date: 20 Mar 2021
Reviewer's report:
This is an interesting and well written paper regarding the impact of testosterone in male patients
with hepatitis B virus related acute on chronic liver failure (HBV-ACLF). The authors evaluated
160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB)
and 106 healthy controls (HC) and they found that low serum levels of total testosterone were
associated with increased stage of ascites, hepatic encephalopathy, MELD and HBVB-ACLF
scores, while low testosterone (<142.39 ng/dL) was a risk factor for both the composite outcome
and for death alone within 90 days.
However, there are some issues which should be addressed by the authors
1) SHBG needs abbreviation
2) Declaration of Helsinki needs update
3) The authors stated that the patients underwent artificial liver support system. Can they clarify
better this issue? For how long did they receive this support? How this support can affect their
results?
4) Did the authors have any data regarding the causes of ACLF? Infection, G.I. bleeding etc
5) “MELD and COSSH ACLF were calculated using the most abnormal value”. Is it true? Na
d not at baseline similar to hormones evaluation?
6) MELD score was MELD-Na or original?
7) SPSS version needs update
8) Page 10: SHBG is not a hormone
9) Any data regarding antiviral therapy?
10) Table 1: How did the authors explain that cortisol was lower in early stage that middle and
end-stage of HBV-ACLF? Similar comment for DHEAS
11) Table 3: Estimate? 95%CI?
12) Total testosterone should be excluded from Table 4
13)  In cox regression analysis for the outcome all the variables significantly associated with the
outcome in univariate analysis should be included
Please review this paper.
user
Title: Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B
virus-related acute-on-chronic liver failure in males
Version: 1 Date: 20 Mar 2021
Reviewer's report:
This is an interesting and well written paper regarding the impact of testosterone in male patients
with hepatitis B virus related acute on chronic liver failure (HBV-ACLF). The authors evaluated
160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB)
and 106 healthy controls (HC) and they found that low serum levels of total testosterone were
associated with increased stage of ascites, hepatic encephalopathy, MELD and HBVB-ACLF
scores, while low testosterone (<142.39 ng/dL) was a risk factor for both the composite outcome
and for death alone within 90 days.
However, there are some issues which should be addressed by the authors
1) SHBG needs abbreviation
2) Declaration of Helsinki needs update
3) The authors stated that the patients underwent artificial liver support system. Can they clarify
better this issue? For how long did they receive this support? How this support can affect their
results?
4) Did the authors have any data regarding the causes of ACLF? Infection, G.I. bleeding etc
5) “MELD and COSSH ACLF were calculated using the most abnormal value”. Is it true? Na
d not at baseline similar to hormones evaluation?
6) MELD score was MELD-Na or original?
7) SPSS version needs update
8) Page 10: SHBG is not a hormone
9) Any data regarding antiviral therapy?
10) Table 1: How did the authors explain that cortisol was lower in early stage that middle and
end-stage of HBV-ACLF? Similar comment for DHEAS
11) Table 3: Estimate? 95%CI?
12) Total testosterone should be excluded from Table 4
13)  In cox regression analysis for the outcome all the variables significantly associated with the
outcome in univariate analysis should be included
assistant