Title: Risk Factors Affecting the Incidence of CMV Infection in Recipients after Living Donor
Liver Transplantation
Version: 2 Date: 03 Apr 2025
Reviewer's report:
Major Comments
1.  The single-center design (Ain Shams University, Egypt) limits generalizability to broader
populations. Regional practices (e.g., lack of CMV prophylaxis) and a homogeneous cohort
(HCV-related ESLD) may not reflect global LT populations.
2. Retrospective Design Limitations:
- Potential selection bias and unmeasured confounders (e.g., immunosuppression trough levels,
viral load dynamics) are not addressed. A discussion on how confounders were controlled (e.g.,
multivariate adjustments) is needed.
3. The absence of CMV prophylaxis deviates from international guidelines. This critical
omission should be highlighted as a limitation, as it may explain higher infection rates compared
to studies using prophylaxis.
4. Focus on CMV IgM Over IgG:
- CMV IgG serostatus (donor/recipient mismatch) is a well-established risk factor, yet the study
focuses on IgM. Justification for prioritizing IgM (prone to false positives) and its clinical
relevance post-LT requires elaboration.
5. While CMV infection precedes rejection, causality is not proven. The bidirectional
relationship (CMV reactivation due to rejection treatment vs. CMV-triggered rejection) needs
nuanced discussion.
Minor Comments
1.  Clarify the rationale for test selection (e.g., Mann-Whitney vs. t-test). Borderline significant
p-values (e.g., MELD score: p=0.041) should be interpreted cautiously to avoid overstatement.
2. Differentiate "CMV infection" (viremia) from "CMV disease" (symptomatic) consistently, as
outcomes and management differ.
3. Tables 1–3 have alignment issues (e.g., merged cells, inconsistent spacing). Streamlining
these would enhance readability.
4. Figures 1–3 are referenced but not sufficiently described in the text. A brief summary of key
findings (e.g., timing of infections in Figure 3) would strengthen the results section.
Limitations Not Acknowledged
1. The study protocol’s omission of CMV prophylaxis (unusual in modern LT care) likely
elevates infection rates, skewing comparisons with other studies.
2. Results may not apply to non-HCV ESLD etiologies (e.g., NASH, ALD) or regions with
differing donor/recipient CMV serostatus profiles.
3. IgM Reliability:
- Preoperative CMV IgM was confirmed by PCR only in positive cases. False negatives/positives
in IgM testing could bias results; this limitation is unaddressed.
4.  Follow-up duration ranged widely (12–84 months). Late CMV infections or delayed rejection
events may be underrepresented.
Title: Risk Factors Affecting the Incidence of CMV Infection in Recipients after Living Donor
Liver Transplantation
Version: 2 Date: 03 Apr 2025
Reviewer's report:
Major Comments
1.  The single-center design (Ain Shams University, Egypt) limits generalizability to broader
populations. Regional practices (e.g., lack of CMV prophylaxis) and a homogeneous cohort
(HCV-related ESLD) may not reflect global LT populations.
2. Retrospective Design Limitations:
- Potential selection bias and unmeasured confounders (e.g., immunosuppression trough levels,
viral load dynamics) are not addressed. A discussion on how confounders were controlled (e.g.,
multivariate adjustments) is needed.
3. The absence of CMV prophylaxis deviates from international guidelines. This critical
omission should be highlighted as a limitation, as it may explain higher infection rates compared
to studies using prophylaxis.
4. Focus on CMV IgM Over IgG:
- CMV IgG serostatus (donor/recipient mismatch) is a well-established risk factor, yet the study
focuses on IgM. Justification for prioritizing IgM (prone to false positives) and its clinical
relevance post-LT requires elaboration.
5. While CMV infection precedes rejection, causality is not proven. The bidirectional
relationship (CMV reactivation due to rejection treatment vs. CMV-triggered rejection) needs
nuanced discussion.
Minor Comments
1.  Clarify the rationale for test selection (e.g., Mann-Whitney vs. t-test). Borderline significant
p-values (e.g., MELD score: p=0.041) should be interpreted cautiously to avoid overstatement.
2. Differentiate "CMV infection" (viremia) from "CMV disease" (symptomatic) consistently, as
outcomes and management differ.
3. Tables 1–3 have alignment issues (e.g., merged cells, inconsistent spacing). Streamlining
these would enhance readability.
4. Figures 1–3 are referenced but not sufficiently described in the text. A brief summary of key
findings (e.g., timing of infections in Figure 3) would strengthen the results section.
Limitations Not Acknowledged
1. The study protocol’s omission of CMV prophylaxis (unusual in modern LT care) likely
elevates infection rates, skewing comparisons with other studies.
2. Results may not apply to non-HCV ESLD etiologies (e.g., NASH, ALD) or regions with
differing donor/recipient CMV serostatus profiles.
3. IgM Reliability:
- Preoperative CMV IgM was confirmed by PCR only in positive cases. False negatives/positives
in IgM testing could bias results; this limitation is unaddressed.
4.  Follow-up duration ranged widely (12–84 months). Late CMV infections or delayed rejection
events may be underrepresented.
Please review this paper.
user
Title: Risk Factors Affecting the Incidence of CMV Infection in Recipients after Living Donor
Liver Transplantation
Version: 2 Date: 03 Apr 2025
Reviewer's report:
Major Comments
1.  The single-center design (Ain Shams University, Egypt) limits generalizability to broader
populations. Regional practices (e.g., lack of CMV prophylaxis) and a homogeneous cohort
(HCV-related ESLD) may not reflect global LT populations.
2. Retrospective Design Limitations:
- Potential selection bias and unmeasured confounders (e.g., immunosuppression trough levels,
viral load dynamics) are not addressed. A discussion on how confounders were controlled (e.g.,
multivariate adjustments) is needed.
3. The absence of CMV prophylaxis deviates from international guidelines. This critical
omission should be highlighted as a limitation, as it may explain higher infection rates compared
to studies using prophylaxis.
4. Focus on CMV IgM Over IgG:
- CMV IgG serostatus (donor/recipient mismatch) is a well-established risk factor, yet the study
focuses on IgM. Justification for prioritizing IgM (prone to false positives) and its clinical
relevance post-LT requires elaboration.
5. While CMV infection precedes rejection, causality is not proven. The bidirectional
relationship (CMV reactivation due to rejection treatment vs. CMV-triggered rejection) needs
nuanced discussion.
Minor Comments
1.  Clarify the rationale for test selection (e.g., Mann-Whitney vs. t-test). Borderline significant
p-values (e.g., MELD score: p=0.041) should be interpreted cautiously to avoid overstatement.
2. Differentiate "CMV infection" (viremia) from "CMV disease" (symptomatic) consistently, as
outcomes and management differ.
3. Tables 1–3 have alignment issues (e.g., merged cells, inconsistent spacing). Streamlining
these would enhance readability.
4. Figures 1–3 are referenced but not sufficiently described in the text. A brief summary of key
findings (e.g., timing of infections in Figure 3) would strengthen the results section.
Limitations Not Acknowledged
1. The study protocol’s omission of CMV prophylaxis (unusual in modern LT care) likely
elevates infection rates, skewing comparisons with other studies.
2. Results may not apply to non-HCV ESLD etiologies (e.g., NASH, ALD) or regions with
differing donor/recipient CMV serostatus profiles.
3. IgM Reliability:
- Preoperative CMV IgM was confirmed by PCR only in positive cases. False negatives/positives
in IgM testing could bias results; this limitation is unaddressed.
4.  Follow-up duration ranged widely (12–84 months). Late CMV infections or delayed rejection
events may be underrepresented.
assistant