Review for 10.1186/s12876-025-03910-2 (2025)

Title: Effectiveness and safety evaluation of terlipressin in the treatment of intestinal paralysis
in end-stage liver disease
Version: 0 Date: 07 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The study is conducted at a single institution (the Second Affiliated Hospital of Chongqing
Medical University), which may limit the generalizability of the findings to broader populations,
particularly those in different geographic locations or with diverse healthcare access. Multi-
center studies would help to address this limitation.
-The patients in the prospective study are assigned to either the terlipressin group or the
conventional treatment group according to their wishes. This introduces a potential selection
bias, as patients who opt for terlipressin treatment may have different characteristics or
expectations than those in the conventional group. Randomized controlled trials (RCTs) would
eliminate this bias and provide more reliable evidence.
-While the study compares terlipressin with conventional treatment, there is no mention of
including a placebo or another agent (e.g., somatostatin) as a control group. Having a placebo
group would help to isolate the specific effects of terlipressin versus the natural course of the
disease or the effect of conventional treatments alone.
-The study provides no clear mention of the follow-up period post-treatment. It would be
beneficial to evaluate the long-term effectiveness and safety of terlipressin, as the resolution of
dynamic intestinal obstruction could potentially change over time, and delayed adverse effects
may emerge.
-The study does not mention subgroup analysis based on patient characteristics (e.g., age,
severity of ESLD, underlying comorbidities) that may influence treatment outcomes. Subgroup
analysis would provide more detailed insights into which specific groups of patients benefit
most from terlipressin treatment.
-The sample size of the study (especially in the exploratory phase) is not clearly stated. Without
an adequate sample size, the study's statistical power may be limited, which could impact the
significance of the results. It is important to ensure that the study is powered sufficiently to detect
meaningful differences between groups.
-While diarrhea is mentioned as a common adverse effect of terlipressin, the study could benefit
from further exploration of how this specific side effect may affect the clinical outcomes in
patients with ESLD. Given the potential impact of diarrhea on patient comfort and the underlying
liver disease, a deeper evaluation of this adverse effect is warranted.
-The discussion speculates on the mechanisms behind terlipressin's effects (e.g., its impact on
smooth muscle, peritonitis-induced edema, bacterial translocation, etc.), but there is limited
direct evidence from the study itself to support these claims. While these hypotheses are
reasonable, more detailed discussion or references to specific mechanisms from prior literature
would bolster the argument.
-The discussion mentions that "almost no serious adverse events were reported," but the
data on adverse events is quite limited. While the safety of terlipressin seems favorable,
more information on the adverse events observed (e.g., diarrhea frequency, blood pressure
fluctuations, or peripheral ischemia) would add clarity to the safety profile, especially in the
long term. Further exploration of how side effects were managed would also be beneficial.
-There is no mention of the long-term follow-up of the patients treated with terlipressin. Given
the chronic nature of ESLD, understanding the duration of the treatment effects and monitoring
for delayed adverse events or complications would add value to the study. The absence of this
information leaves the long-term safety and efficacy of terlipressin unclear.
-The discussion mentions positive outcomes, such as the 93.8% effectiveness rate of terlipressin,
but it could benefit from a more in-depth statistical analysis or interpretation of these results.
For example, comparison between groups in terms of specific adverse events, the variability in
the time to symptom resolution, or subgroup analyses could offer a more nuanced understanding
of the treatment's impact.