Title: Sleep disturbance in patients with cirrhosis and transjugular intrahepatic portosystemic
shunt
Version: 3 Date: 19 Aug 2024
Reviewer's report:
Ming Zhao et al. wrote a paper on the incidence of sleep disturbances (SD) in patients with
cirrhosis undergoing TIPS implantation.
The topic of the manuscript is of clinical importance, as patients with cirrhosis - and especially
those at risk of or with a diagnosis of hepatic encephalopathy (HE) - commonly suffer from SD.
Consequently, it may well be that TIPS implantation - a known risk factor for HE - triggers or
worsens SD.
To assess the incidence of post-TIPS HE, patients with SD prior to TIPS were excluded, although
it affects up to 70% of patients with cirrhosis, as was also stated in the manuscript. On the one
hand, this led to exclusion of most patients with the TIPS indication ascites and Child C cirrhosis,
as patients with ascites a) often suffer from SD due to abdominal discomfort and b) have an
increased risk of HE, and often suffer from MHE due to diuretic treatment. It would have been of
interest if preexisting (mild) SD worsens after TIPS, especially in the large population of patients
with ascites, or may even improve due to improvement of ascites and abdominal discomfort.
Additionally, I have some further issues that should be addressed:
- The authors state that HE was assessed using West-Haven criteria. Indeed, it was not, as the
West Haven classification categorizes HE into 5 grades: grade 0/mHE, grade I/subclinical HE,
and the clinical grades II-IV. The word "grade" was never used in the manuscript; "overt" and
"covert" HE are categories used by the ISHEN classification correlating to grades II-IV and
0 of the West Haven classification system. Thus, grade I according to West Haven was never
reported. This should be corrected.
- SD is a symptom of HE - indeed, change of day-night rhythm is a symptom of OHE/HE grade
III. Thus it is unsurprising that both syndromes correlate.
- Higher age, hyperammonemia, presence of diabetes mellitus and sarcopenia are major risk
factors for (post-TIPS) HE. However, data on presence of DM and sarcopenia are missing, as are
pre- and post-TIPS values for ammonia. All manuscripts on HE should include ammonia values.
- TIPS stent diameter significantly correlates with post-TIPS HE risk and is also missing and
should be reported.
- The figure does not provide any additional information that wasn't mentioned in the text of
the manuscript.
- How many patients underwent interventional-radiologic embolization of varices? Reducing
portosystemic shunting may also improve/influence OHE risk and thus improve SD.
- What is the reasoning of the authors for the spontaneous improvement of SD in the affected
patients? How many patients who "spontaneously improved" and suffered from MHE/OHE were
escalated in HE therapy, e.g. did any patients receive antibiotic treatment with rifaximin or
levofloxacin?
Minor issues:
- The text is lacking proof-reading regarding language, formatting and spelling errors.
- Figure 2A is missing the legend of the figure colors.
- Methods section, Hamilton depression scale: The authors write "14 scores" or "18 scores" -
should this mean "points"?
Title: Sleep disturbance in patients with cirrhosis and transjugular intrahepatic portosystemic
shunt
Version: 3 Date: 19 Aug 2024
Reviewer's report:
Ming Zhao et al. wrote a paper on the incidence of sleep disturbances (SD) in patients with
cirrhosis undergoing TIPS implantation.
The topic of the manuscript is of clinical importance, as patients with cirrhosis - and especially
those at risk of or with a diagnosis of hepatic encephalopathy (HE) - commonly suffer from SD.
Consequently, it may well be that TIPS implantation - a known risk factor for HE - triggers or
worsens SD.
To assess the incidence of post-TIPS HE, patients with SD prior to TIPS were excluded, although
it affects up to 70% of patients with cirrhosis, as was also stated in the manuscript. On the one
hand, this led to exclusion of most patients with the TIPS indication ascites and Child C cirrhosis,
as patients with ascites a) often suffer from SD due to abdominal discomfort and b) have an
increased risk of HE, and often suffer from MHE due to diuretic treatment. It would have been of
interest if preexisting (mild) SD worsens after TIPS, especially in the large population of patients
with ascites, or may even improve due to improvement of ascites and abdominal discomfort.
Additionally, I have some further issues that should be addressed:
- The authors state that HE was assessed using West-Haven criteria. Indeed, it was not, as the
West Haven classification categorizes HE into 5 grades: grade 0/mHE, grade I/subclinical HE,
and the clinical grades II-IV. The word "grade" was never used in the manuscript; "overt" and
"covert" HE are categories used by the ISHEN classification correlating to grades II-IV and
0 of the West Haven classification system. Thus, grade I according to West Haven was never
reported. This should be corrected.
- SD is a symptom of HE - indeed, change of day-night rhythm is a symptom of OHE/HE grade
III. Thus it is unsurprising that both syndromes correlate.
- Higher age, hyperammonemia, presence of diabetes mellitus and sarcopenia are major risk
factors for (post-TIPS) HE. However, data on presence of DM and sarcopenia are missing, as are
pre- and post-TIPS values for ammonia. All manuscripts on HE should include ammonia values.
- TIPS stent diameter significantly correlates with post-TIPS HE risk and is also missing and
should be reported.
- The figure does not provide any additional information that wasn't mentioned in the text of
the manuscript.
- How many patients underwent interventional-radiologic embolization of varices? Reducing
portosystemic shunting may also improve/influence OHE risk and thus improve SD.
- What is the reasoning of the authors for the spontaneous improvement of SD in the affected
patients? How many patients who "spontaneously improved" and suffered from MHE/OHE were
escalated in HE therapy, e.g. did any patients receive antibiotic treatment with rifaximin or
levofloxacin?
Minor issues:
- The text is lacking proof-reading regarding language, formatting and spelling errors.
- Figure 2A is missing the legend of the figure colors.
- Methods section, Hamilton depression scale: The authors write "14 scores" or "18 scores" -
should this mean "points"?
Please review this paper.
user
Title: Sleep disturbance in patients with cirrhosis and transjugular intrahepatic portosystemic
shunt
Version: 3 Date: 19 Aug 2024
Reviewer's report:
Ming Zhao et al. wrote a paper on the incidence of sleep disturbances (SD) in patients with
cirrhosis undergoing TIPS implantation.
The topic of the manuscript is of clinical importance, as patients with cirrhosis - and especially
those at risk of or with a diagnosis of hepatic encephalopathy (HE) - commonly suffer from SD.
Consequently, it may well be that TIPS implantation - a known risk factor for HE - triggers or
worsens SD.
To assess the incidence of post-TIPS HE, patients with SD prior to TIPS were excluded, although
it affects up to 70% of patients with cirrhosis, as was also stated in the manuscript. On the one
hand, this led to exclusion of most patients with the TIPS indication ascites and Child C cirrhosis,
as patients with ascites a) often suffer from SD due to abdominal discomfort and b) have an
increased risk of HE, and often suffer from MHE due to diuretic treatment. It would have been of
interest if preexisting (mild) SD worsens after TIPS, especially in the large population of patients
with ascites, or may even improve due to improvement of ascites and abdominal discomfort.
Additionally, I have some further issues that should be addressed:
- The authors state that HE was assessed using West-Haven criteria. Indeed, it was not, as the
West Haven classification categorizes HE into 5 grades: grade 0/mHE, grade I/subclinical HE,
and the clinical grades II-IV. The word "grade" was never used in the manuscript; "overt" and
"covert" HE are categories used by the ISHEN classification correlating to grades II-IV and
0 of the West Haven classification system. Thus, grade I according to West Haven was never
reported. This should be corrected.
- SD is a symptom of HE - indeed, change of day-night rhythm is a symptom of OHE/HE grade
III. Thus it is unsurprising that both syndromes correlate.
- Higher age, hyperammonemia, presence of diabetes mellitus and sarcopenia are major risk
factors for (post-TIPS) HE. However, data on presence of DM and sarcopenia are missing, as are
pre- and post-TIPS values for ammonia. All manuscripts on HE should include ammonia values.
- TIPS stent diameter significantly correlates with post-TIPS HE risk and is also missing and
should be reported.
- The figure does not provide any additional information that wasn't mentioned in the text of
the manuscript.
- How many patients underwent interventional-radiologic embolization of varices? Reducing
portosystemic shunting may also improve/influence OHE risk and thus improve SD.
- What is the reasoning of the authors for the spontaneous improvement of SD in the affected
patients? How many patients who "spontaneously improved" and suffered from MHE/OHE were
escalated in HE therapy, e.g. did any patients receive antibiotic treatment with rifaximin or
levofloxacin?
Minor issues:
- The text is lacking proof-reading regarding language, formatting and spelling errors.
- Figure 2A is missing the legend of the figure colors.
- Methods section, Hamilton depression scale: The authors write "14 scores" or "18 scores" -
should this mean "points"?
assistant