TIPS in Older Adults: Reserve-Based Risk Stratification and Practical Approach
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsDear authors,
You can find my criticisms in the file I uploaded.
Best regards
Comments for author File: 
Comments.pdf
The English could be improved to more clearly express the research.
Author Response
Comments 1: The conceptual distinction between chronological age and biological reserve could be articulated more clearly. The manuscript uses related constructs (biological age, frailty, sarcopenia, cognitive reserve, cardiopulmonary reserve) without clarifying their relationships. Please align with established geriatric frameworks (CGA, frailty phenotype, deficit accumulation).
Response 1: We agree and have strengthened the theoretical foundation by explicitly defining “multidomain physiological reserve” and clarifying how each construct (frailty, sarcopenia, cognitive vulnerability, cardiopulmonary–renal reserve) maps onto established geriatric frameworks. We added (i) a concise definition paragraph in the Introduction that maps our reserve model to Comprehensive Geriatric Assessment (CGA), the frailty phenotype model, and the deficit accumulation model, while emphasizing pragmatic implementation in hepatology practice (Page 3, Line 125-135).
Comment 2: The evidence synthesis could be more critical; please explicitly address limitations such as retrospective design, selection bias, heterogeneity in procedural techniques, and inconsistent age thresholds.
Response 2: We agree and revised Section 2 to explicitly address methodological limitations and explain why results differ across studies. We added a dedicated “Interpretation and limitations” paragraph highlighting (i) retrospective designs and selection bias (older TIPS candidates being highly selected), (ii) heterogeneity in indications (bleeding vs ascites) and procedural strategies (stent type/diameter, degree of decompression, adjunct embolization), (iii) inconsistent age thresholds (≥65/70/75/80), and (iv) incomplete measurement of geriatric determinants (frailty, sarcopenia, cognition, polypharmacy, caregiver support), limiting causal inference and universal cut-off recommendations (Page 5, Line 221-232).
Comment 3: The pathway is innovative but needs operational detail. Which frailty tool should be used (LFI vs Fried)? How should sarcopenia be defined (CT-SMI vs bedside)? Which cognitive tests (PHES/Stroop/MoCA)? Which cardiac parameters trigger caution/avoidance?
Response 3: We agree and have operationalized the pathway to improve bedside applicability. We added an “Operational definitions and suggested tools” subsection to Section 4, providing a tiered approach (preferred tool and acceptable alternatives) for: frailty (LFI preferred; Fried phenotype/SPPB as alternatives), sarcopenia (CT-based SMI preferred; psoas metrics or bedside surrogates where imaging not feasible), neurocognitive screening (prior OHE history plus covert HE tools when feasible; pragmatic cognition screens as adjuncts), and cardiopulmonary evaluation (ECG + comprehensive echocardiography including diastolic assessment; screening for pulmonary hypertension; example triggers for heightened caution). We intentionally framed thresholds as pragmatic “trigger points” rather than absolute exclusion cutoffs, acknowledging center-level variability and the observational nature of evidence (Page 10, Line 409-438).
Comment 4: Some sections would benefit from a better balance between risks and potential benefits (ascites control, reduced bleeding, quality of life in refractory ascites).
Response 4: We agree and revised the Introduction and Clinical Pathway sections to explicitly acknowledge potential benefits of TIPS in appropriately selected older adults, including improved ascites control, reduced recurrence of variceal bleeding, and potential quality-of-life gains (Page 2, Line 63-71). This strengthens the manuscript’s central message that the goal is not age-based restriction but improved selection and risk mitigation.
Comment 5: The title is accurate but could potentially be shortened.
Response 5: We agree and shortened the title to improve readability with “TIPS in Older Adults: Reserve-Based Risk Stratification and Practical Approach”.
Comment 6: The abstract should explicitly indicate this is a narrative review. Include the types of studies reviewed. Add a brief statement on clinical implications.
Response 6: We agree and revised the abstract to (i) explicitly state that this is a narrative review (Page 1, Line 28-29), (ii) briefly describe the evidence base (observational cohorts, registry analyses, and systematic reviews/meta-analyses) (Page 1, Line 13-14), and (iii) add a sentence on how the proposed pathway informs patient selection, procedural planning, and post-procedural monitoring (Page 1, Line 30-32) .
Comment 7: The manuscript suggests outcomes worsen particularly >70 years; clarify why this threshold appears relevant. Also strengthen the transition to the proposed framework by emphasizing the gap in current guidelines regarding geriatric vulnerabilities.
Response 7: We agree and added a concise explanation that the commonly used ≥70-year threshold likely reflects a combination of biological aging processes and study-level design/selection patterns rather than a universal physiological boundary. We also strengthened the rationale for our framework by explicitly stating that existing guidance primarily emphasizes liver disease severity and procedural considerations, while providing limited operational detail on geriatric vulnerabilities (frailty, cognition, polypharmacy), which our pathway aims to address (Page 2, Line 75-86).
Reviewer 2 Report
Comments and Suggestions for AuthorsStrengths of the manuscript
The clinical relevance of the topic due to aging of the global population with liver cirrhosis
Shifting the conceptual framework away from chronological age to multidomain reserve fits both geriatric and precision-medicine thinking
The manuscript contains very well-defined sections that are clinically relevant‚ even for those not specialized․
Elucidating hepatic encephalopathy as a key complication‚ and adding mechanistic framing and a pathway figure‚ have improved the manuscript's value related to education․
Additional suggestions:
Even with a narrative review‚ the broad conclusions (e․g․ "age is not an absolute contraindication"‚ "advanced age increases HE/mortality/readmissions"‚ "reserve-based stratification should guide actions") depend on the evidence and not selectively sampled. The introduction notes the heterogeneity and incompleteness of geriatric determinants in this research area‚ highlighting the need for transparent selection‚ particularly when the literature does not have a settled consensus․
In the "Search strategy and study selection" section‚ indicate the databases searched‚ the dates‚ the search terms‚ the criteria for inclusion/exclusion of human studies‚ older patients‚ TIPS indications‚ and other endpoints (post-TIPS HE‚ mortality‚ readmissions‚ cardiac and renal events) and the hierarchy of the guidelines selected․
Author Response
Comment 1: Even with a narrative review‚ the broad conclusions (e․g․ "age is not an absolute contraindication"‚ "advanced age increases HE/mortality/readmissions"‚ "reserve-based stratification should guide actions") depend on the evidence and not selectively sampled. The introduction notes the heterogeneity and incompleteness of geriatric determinants in this research area‚ highlighting the need for transparent selection‚ particularly when the literature does not have a settled consensus․ In the "Search strategy and study selection" section‚ indicate the databases searched‚ the dates‚ the search terms‚ the criteria for inclusion/exclusion of human studies‚ older patients‚ TIPS indications‚ and other endpoints (post-TIPS HE‚ mortality‚ readmissions‚ cardiac and renal events) and the hierarchy of the guidelines selected․
Response 1: Thank you for this important suggestion. We agree that, even for a narrative review, transparency regarding evidence identification and selection is necessary to minimize the risk of selective citation and to allow readers to understand how the conclusions were derived. We have therefore expanded the “2.1. Search strategy and study selection” section (Page 3-4, Line 139-165 to specify: (i) the databases searched and the date range, (ii) the complete search terms and key synonyms used for older age and TIPS, (iii) inclusion/exclusion criteria covering population (cirrhosis), age definitions, indications (variceal bleeding/ascites), and endpoints (post-TIPS HE, mortality, readmissions, cardiac and renal events), and (iv) our approach to guideline selection and prioritization.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsDear authors,
It looks like all my corrections have been made.
Best regards
Comments on the Quality of English LanguageThe English could be improved to more clearly express the research.
Author Response
Response to Editor's Comment
Comment: The manuscript identifies as a "narrative review," yet Section 2.1 uses "systematic review" methods (detailed databases, search formulas, inclusion criteria). To resolve this contradiction: if intended as a systematic review, PRISMA guidelines and a flow diagram are required; if narrative, revise the methodology to avoid misleading readers.
Response: Thank you for this helpful comment. Upon reviewing the manuscript, we realize that Section 2.1 was written with more of a systematic review-style search strategy than is appropriate for a narrative review. To resolve this, we have revised Section 2.1 to avoid any potential misinterpretation of the methodology as systematic. Specifically, we have removed search formulas and inclusion criteria, and clarified that the search process was designed to be comprehensive but narrative in nature.
Author Response File: 
Author Response.docx
