Frailty in hepatobiliary and pancreatic (HBP) surgery: a narrative review toward an HBP-specific, implementation-oriented framework

Introduction

With global demographic shifts, the number of operations for hepatobiliary and pancreatic (HBP) malignancies, including pancreatic cancer, hepatocellular carcinoma, and cholangiocarcinoma, continues to increase (1). These procedures are anatomically complex and remain associated with substantial postoperative complication rates (2). Comorbidity burden and reduced physiological reserve further amplify perioperative risk. Conventional indices such as the American Society of Anesthesiologists (ASA) Physical Status and the Model for End Stage Liver Disease capture organ function and disease severity, but they may not adequately reflect systemic vulnerability and the capacity for recovery in high-stress surgical pathways (2-4). Frailty has therefore gained increasing attention as a predictor of perioperative outcomes. Frailty is commonly defined as a multidimensional syndrome that reflects biological age and spans physical, psychological, and social domains (5,6) (Figure 1). In surgical oncology, malignancy-related inflammation, sarcopenia, and malnutrition may interact to accelerate frailty progression (7). Sarcopenia is a core component and is assessed using established consensus criteria (8). Although frailty has traditionally been framed within geriatric medicine, vulnerability in HBP surgery often diverges from classical age-related frailty because it is shaped by disease- and procedure-specific stressors. Cholestasis with jaundice, recurrent infection such as cholangitis, tumor-associated inflammation, hepatic dysfunction, portal hypertension, and extensive resection can increase metabolic demand, intensify catabolism, and impair recovery. In this setting, frailty reflects not only age-related physiologic decline but also disease-modified stress biology that may not be fully captured by generic frailty instruments alone. Existing frailty tools generally follow two main approaches. The deficit accumulation model, exemplified by the Frailty Index and the Clinical Frailty Scale, measures the accumulation of health deficits (9-11). The phenotypic model depends on performance-based measures such as grip strength and gait speed, with Fried criteria being the most widely used (12). Practical tools have also been employed in HBP settings, including the modified Frailty Index (mFI) and the Liver Frailty Index (Figure 2) (13-16). Frailty assessed by current indices is consistently linked to postoperative complications, delayed recovery, longer hospital stays, and increased mortality (17). In parallel, blood-based composite markers, such as the C-reactive protein-to-albumin ratio and the Geriatric Nutritional Risk Index, can reflect both inflammation and nutritional status and may complement traditional frailty measures in HBP populations (18). However, important limitations remain. Definitions and thresholds vary across studies, assessment timing is inconsistent, and many commonly used tools underrepresent inflammatory and nutritional biology that is central to HBP malignancies and advanced liver disease. As a result, frailty assessment in HBP practice remains difficult to standardize and is not yet well integrated into perioperative workflows. Accordingly, this narrative review was designed not to provide an exhaustive catalog of frailty instruments, but to critically synthesize current evidence on frailty in HBP surgery and liver transplantation, appraise the strengths and limitations of existing approaches, and propose an implementation-oriented HBP-specific framework, “HBP onco-frailty”. Within this framework, vulnerability is organized across four interrelated domains—sarcopenia, malnutrition, impaired physical function, and systemic inflammation—to link risk assessment with actionable perioperative optimization and priorities for future validation (Figure 3). We present this article in accordance with the Narrative Review reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0138/rc).

Figure 1 Multidimensional components of frailty. Venn diagram showing the overlap among physical (e.g., sarcopenia, mobility loss), psychological (e.g., depression, cognitive decline), and social (e.g., isolation) domains. This framework illustrates the complex, multidimensional nature of frailty in geriatric surgical patients.

Figure 2 Comparative overview of frailty models. Schematic comparison of the Fried phenotype model and Rockwood’s deficit accumulation model. Highlights include core domains, strengths, limitations, and clinical applicability. The phenotype model focuses on function; the deficit model reflects cumulative health burden. CHS, Cardiovascular Health Study.

Figure 3 Shift to HBP-specific frailty (HBP onco-frailty). Conceptual model contrasting conventional frailty (sarcopenia, malnutrition, physical function) with HBP onco-frailty, which includes systemic inflammation as a fourth domain. This expanded model better reflects tumor-related vulnerability in HBP surgery. HBP, hepatobiliary and pancreatic.

Methods

Review scope and approach

This narrative review aimed to critically synthesize and contextualize the literature on frailty in HBP surgery and liver transplantation, with emphasis on biologically relevant correlates, clinical implications, and perioperative decision-making. Because the available literature spans heterogeneous diseases, procedures, frailty instruments, and outcome definitions, a narrative approach was selected to allow integration of empirical evidence with mechanistic and implementation-oriented interpretation. Unlike a systematic review, this format was intended to provide a clinically oriented synthesis while explicitly acknowledging the limitations inherent to non-exhaustive evidence selection. The objective was not to provide an exhaustive catalog of all frailty-related publications, but to identify and critically appraise clinically informative evidence relevant to frailty assessment, biologic vulnerability, and perioperative optimization in HBP surgery and liver transplantation.

Literature search and evidence selection

A standalone literature search strategy was developed before evidence synthesis. We searched PubMed, Embase, and Google Scholar for publications from 1 January 2010 through 31 December 2025. Controlled vocabulary and free-text terms were combined across three concept blocks: (I) HBP surgery or transplantation (“hepatectomy”, “hepatic resection”, “pancreatectomy”, “pancreatic resection”, “biliary surgery”, “hepato*”, “pancrea*”, “cholangi*”, “liver transplantation”); (II) frailty and functional assessment (“frailty”, “Clinical Frailty Scale”, “CFS”, “Short Physical Performance Battery”, “SPPB”, “Liver Frailty Index”, “LFI”, “modified Frailty Index”, “mFI”); and (III) biological correlates (“sarcopenia”, “malnutrition”, “inflammation”, “C-reactive protein”, “CRP”, “CRP-to-albumin ratio”, “CAR”, “Geriatric Nutritional Risk Index”, “GNRI”, “albumin”). An English-language restriction was applied, and no study-design filters were used. In addition to bibliographic database searches, we hand-searched the reference lists of key articles and relevant reviews. We also reviewed relevant professional society statements, consensus recommendations, and perioperative guidance documents where applicable, particularly when these addressed frailty screening, prehabilitation, perioperative optimization, enhanced recovery pathways, or transplant-related assessment in HBP practice. Eligibility criteria were prespecified. We included studies of adult patients undergoing HBP surgery or liver transplantation that reported associations between frailty-related assessments and clinically meaningful outcomes, including postoperative complications, functional recovery, prognosis, treatment tolerance, length of stay, readmission, or survival. Frailty-related assessments included validated instruments such as the Fried phenotype, Clinical Frailty Scale, Short Physical Performance Battery, mFI, Liver Frailty Index, and the Japanese version of the Cardiovascular Health Study (CHS) criteria. We also included studies examining nutritional and inflammatory markers when these were explicitly analyzed in relation to frailty, vulnerability, or perioperative resilience. Original studies, systematic reviews, meta-analyses, and relevant society or consensus documents were eligible. We excluded editorials, commentaries, case reports, conference abstracts, non-English articles, and studies that did not primarily address frailty-related assessment in HBP surgical or transplant populations. Because this was a narrative review, study identification and selection were not intended to be exhaustive, and we did not apply a formal risk-of-bias tool. However, to improve transparency and minimize subjective selection, evidence selection was guided by prespecified relevance criteria. Priority was given to studies with clearly defined HBP or transplant populations, validated or clearly described frailty-related assessments, and clinically meaningful perioperative or prognostic outcomes. When multiple studies addressed similar questions, we preferentially incorporated studies with stronger methodological features, including prospective design, larger cohorts, systematic reviews, meta-analyses, or formal consensus/guideline methodology. We also sought to include both supportive and conflicting findings to avoid an overly affirmative synthesis. Evidence was then organized using a four-domain framework—sarcopenia, malnutrition, impaired physical function, and systemic inflammation—because these domains recurrently intersect in HBP oncology and transplantation and provide a clinically actionable structure for interpretation. Synthesis emphasized predictive performance, feasibility, workflow compatibility, and disease- and procedure-specific considerations relevant to HBP surgery. Particular attention was paid to whether a given measure offered interpretability beyond conventional perioperative assessment and whether it could plausibly be linked to targeted interventions such as nutrition support, infection control, prehabilitation, or treatment-timing decisions. A structured summary of the search framework, sources, eligibility criteria, and selection process is provided in Table 1. The full PubMed search strategy is presented in Table S1 to enhance transparency and reproducibility.

Evidence synthesis and key findings

Landscape and limitations of current evidence

Evidence on frailty in HBP surgery spans diverse diseases, procedures, and perioperative pathways, and it uses multiple frailty instruments as well as surrogate domain measures. In oncogeriatric surgical populations, frailty prevalence is higher than in community-dwelling older adults, plausibly reflecting the combined burden of sarcopenia, malnutrition, and cancer-related catabolism (19-21). Across studies, frailty-related assessments are generally associated with clinically relevant outcomes, including infectious complications, delayed recovery, prolonged length of stay, and survival (4,22-26). However, direct comparisons across studies remain limited by substantial heterogeneity in operational definitions, timing of assessment, endpoint selection, and case mix (22-26).

A further limitation is that much of the literature is retrospective, often single-center, and variably enriched for highly selected operative candidates. As a result, observed associations may reflect not only biologic vulnerability itself but also differences in treatment selection, baseline disease burden, and institutional perioperative practice. Predictive performance can also vary by operative context; measures that appear useful in high-stress pathways may offer less incremental value in lower-stress settings or when conventional perioperative risk assessment is already robust (27). These constraints argue against overinterpreting any single instrument as definitive. Recent society-level guidance supports perioperative optimization, enhanced recovery, and structured assessment of older or high-risk surgical patients, but HBP-specific frailty guidance remains limited (28-32). Accordingly, rather than treating existing tools as interchangeable, we synthesize the literature using a domain-based framework that prioritizes clinical interpretability, biologic plausibility, and implementation relevance. We therefore organize the evidence around four interrelated domains that recur across HBP oncology and transplantation: sarcopenia or muscle vulnerability, malnutrition, reduced physical function, and systemic inflammation.

Key findings by domain

Sarcopenia and muscle vulnerability

Preoperative sarcopenia, typically assessed using computed tomography (CT)-based body-composition metrics and complemented by simple strength measures when available, is repeatedly associated with major morbidity and slower recovery in high-stress HBP pathways (23-26). Its clinical value is greatest when interpreted as an actionable vulnerability signal rather than a stand-alone label. However, the sarcopenia literature is limited by variability in image-based definitions, measurement level, cutoffs, and whether muscle quantity is assessed alongside muscle strength or performance. This heterogeneity reduces comparability across studies and complicates the adoption of universal thresholds. From an implementation perspective, sarcopenia should prompt early nutrition support and structured prehabilitation, with reassessment integrated into perioperative planning rather than used only for passive risk labeling. This position is directionally consistent with perioperative optimization guidance in major abdominal surgery and enhanced recovery after surgery (ERAS)-based pathways, although HBP-specific validation of sarcopenia-triggered interventions remains incomplete (28,29).

Implementation-ready summary: CT-based muscle assessment, together with simple strength measures when feasible, can be used to identify muscle vulnerability before major HBP resections and in transplant pathways. Findings should trigger early nutrition optimization and prehabilitation planning, while recognizing that standardized cutoffs and intervention thresholds remain insufficiently harmonized.

Malnutrition

Malnutrition reflects limited metabolic reserve and impaired capacity for tissue repair and immune response during perioperative stress. In HBP surgery, nutritional deterioration is often accelerated by biliary obstruction, recurrent cholangitis or pancreatitis, hepatic dysfunction, tumor-related inflammation, and reduced intake during preoperative therapy. Nutritional vulnerability is therefore best interpreted in the context of disease- and procedure-specific stress, and operationalized as an intervention-oriented risk domain. At the same time, the literature varies in how malnutrition is defined, ranging from serum-based surrogates to composite nutritional indices and broader cachexia-related constructs. Albumin-based measures are clinically convenient but may reflect inflammatory burden in addition to nutritional state, which can be a strength for vulnerability assessment but a limitation for mechanistic specificity. Accordingly, nutritional markers should not be interpreted in isolation. Rather, they are most useful when integrated with functional and inflammatory domains (22).

Implementation-ready summary: albumin-based measures and the Geriatric Nutritional Risk Index may help identify patients who should be prioritized for nutrition optimization, perioperative supplementation strategies, and rehabilitation planning, particularly when maintenance of treatment intensity and timely delivery of multimodal therapy are important goals (18,33).

Reduced physical function

Reduced physical function integrates physiologic reserve and resilience under surgical stress and captures actionable vulnerability that comorbidity-focused indices may miss. Comorbidity-based screening, such as the mFI-5, is also linked to malnutrition, body composition, systemic inflammation, and short-term outcomes in surgical oncology cohorts, supporting the need to interpret vulnerability through multiple interacting domains rather than a single score alone (34). Clinician-rated screening and performance-based testing, including the Clinical Frailty Scale and the Short Physical Performance Battery, have demonstrated associations with early complications and subsequent disability risk in surgical populations (35). In liver surgery and transplantation, organ-specific instruments such as the Liver Frailty Index and the revised Japanese CHS may further refine risk identification and complement conventional severity scores (16,36-40). However, functional assessment is also subject to contextual limitations. Performance-based measures can be influenced by pain, ascites, fatigue, biliary sepsis, and short-term treatment effects, and not all studies distinguish between chronic baseline vulnerability and transient functional deterioration. This matters clinically because the latter may still be actionable, but it should not automatically be interpreted as equivalent to fixed frailty.

Implementation-ready summary: when decisions involve high-stress procedures or transplant pathways, incorporate performance-based assessment, and use the Liver Frailty Index when liver disease or transplant candidacy is central. Results should inform prehabilitation intensity, discharge planning, and perioperative resource allocation rather than serve as static exclusion criteria.

Systemic inflammation

Systemic inflammation is a defining domain of onco-frailty in HBP oncology because it amplifies catabolic stress and immune vulnerability and interacts bidirectionally with sarcopenia and malnutrition. In HBP practice, inflammatory burden is often shaped by tumor biology, biliary obstruction, infection-related events, hepatic dysfunction, and treatment-related perturbations. Inflammation can be captured using routinely available biomarkers, including C-reactive protein, albumin, and composite measures such as the C-reactive protein-to-albumin ratio, providing biologic information that is not fully represented by comorbidity-based indices (22).

Nevertheless, inflammatory markers are non-specific. Elevated values may reflect malignancy, cholangitis, postoperative events, or broader intercurrent illness, and the timing of measurement is often inconsistent across studies. Their utility therefore lies less in etiologic attribution than in identifying a clinically meaningful vulnerability state that may require optimization before or during treatment.

Implementation-ready summary: preoperative assessment should include C-reactive protein, albumin, and the C-reactive protein-to-albumin ratio when available to identify inflammation-dominant vulnerability and support risk-adapted optimization, including infection control, biliary drainage when relevant, and integration of nutrition support and prehabilitation.

Tool selection and clinical context

Tool selection should match the clinical setting and the intended decision. In outpatient settings, phenotype-oriented or performance-based instruments are useful for characterizing vulnerability and tracking change over time. In perioperative workflows, objective and quickly calculated indices such as the mFI are often favored for scalability (25,34). When decisions involve high-stress procedures, transplantation candidacy, or the feasibility of multimodal oncologic therapy, performance-based or organ-specific tools, including the Short Physical Performance Battery and the Liver Frailty Index, may provide added discrimination by capturing reserve and disability risk (35-40). Importantly, no single instrument should be assumed to be universally optimal across all HBP settings. Existing guidance in older adults and ERAS-oriented perioperative care supports structured assessment and optimization, but does not establish a single HBP-specific frailty standard (28-30). In practice, the most defensible approach is context-sensitive tool selection combined with multidomain interpretation. Tables 2,3 summarize practical options and suggested use cases.

Disease-specific frailty patterns and biologic enrichment

Pancreatic cancer

Frailty in pancreatic cancer often presents as an inflammation-dominant phenotype driven by systemic inflammation, cachexia, and therapy-associated catabolism. In this context, combining conventional tools such as the Clinical Frailty Scale or the mFI with inflammatory markers, including C-reactive protein-based indices and the C-reactive protein-to-albumin ratio, may improve perioperative risk characterization and align assessment with disease-specific stress biology (41-45). However, most available data remain observational, and incremental predictive benefit over established oncologic and surgical risk models is not yet fully established.

Hepatocellular carcinoma

In hepatocellular carcinoma, frailty frequently arises from cirrhosis-related inflammation, malnutrition, portal hypertensive physiology, and hepatic dysfunction. This creates a vulnerability pattern in which organ dysfunction and metabolic reserve are tightly coupled. The mFI and the Liver Frailty Index can be useful, particularly when sarcopenia and impaired performance are present. However, interpretation should account for the fact that liver-specific physiology may influence performance independent of chronological aging. Biomarker-integrated approaches are being explored to capture combined contributions of liver function, inflammation, and nutritional reserve, but standardization remains limited (46-50).

Cholangiocarcinoma

In cholangiocarcinoma, biliary obstruction, recurrent cholangitis, repeated biliary interventions, and impaired intake can accelerate physiologic decline and heighten inflammatory and nutritional vulnerability. This is a setting in which frailty may be substantially disease-modified and potentially reversible in part with effective drainage, infection control, and nutrition support. The challenge is that frailty assessment may fluctuate with biliary status and timing of evaluation, which complicates interpretation of a single baseline measure. Early identification of modifiable domains can nevertheless support targeted optimization before major surgery or during multimodal treatment (51,52).

Liver transplantation

In transplant candidates, frailty is commonly driven by decompensated liver disease and manifests through sarcopenia, ascites, infection vulnerability, encephalopathy, and reduced physical reserve. In this setting, the Liver Frailty Index complements severity scores, such as Model for End-Stage Liver Disease (MELD) and Child-Pugh, in candidate evaluation and prognostication (53-56). This aligns with liver-disease guidance that treats frailty and sarcopenia as clinically relevant, actionable dimensions rather than secondary observations (30,32). Even so, the boundaries between liver-specific functional impairment and broader frailty remain imperfectly defined, and serial assessment is often more informative than a single timepoint.

Colorectal liver metastases

In patients undergoing hepatectomy for colorectal liver metastases, frailty predicts postoperative complications and survival, and available evidence supports the mFI as an independent prognostic marker in some settings (57,58). However, this literature is smaller and often intermixed with broader oncologic risk factors, so conclusions should remain cautious. Molecular markers, including microRNAs, may further refine vulnerability stratification, but current data remain investigational and should be considered hypothesis-generating rather than implementation-ready (59).

Discussion

Synthesis and clinical interpretation

This narrative review supports frailty as a clinically meaningful predictor of adverse outcomes after high-risk HBP surgery, including hepatic and pancreatic resections (25,60). However, frailty in HBP practice should not be interpreted as a uniform geriatric construct. Rather, vulnerability is frequently modified by disease- and treatment-specific stressors, including cholestasis, infection, portal hypertensive physiology, tumor-related inflammation, hepatic dysfunction, and treatment-related deconditioning. In this setting, generic frailty instruments used in isolation may be insufficient for risk stratification in selected contexts. We therefore propose HBP onco-frailty as an implementation-oriented scaffold that identifies dominant vulnerability domains and links assessment to targeted perioperative optimization, including infection control, nutrition support, prehabilitation, and timing decisions for surgery and multimodal therapy (61,62). This construct is not intended to replace established perioperative scores, but to complement them by capturing systemic vulnerability and physiologic reserve beyond comorbidity burden alone. For routine workflows, streamlined tools such as the mFI and clinician-rated screening such as the Clinical Frailty Scale provide practical entry points, whereas organ-specific instruments such as the Liver Frailty Index may better capture liver-focused vulnerability when hepatectomy or transplant candidacy is central (63,64). Overall, a multidomain approach integrating muscle vulnerability, nutrition, inflammation, and functional capacity offers the most clinically actionable framework for perioperative decision-making and recovery-oriented planning in HBP oncology and transplantation (65). Importantly, this framework should be interpreted as a clinically grounded organizing model rather than a finalized HBP-specific standard. Current evidence supports the relevance of frailty-related assessment in HBP practice, but does not yet define a single universally optimal instrument or operational threshold across all diseases and procedures.

From biology to clinical practice

Positioning inflammatory and nutritional biomarkers

Systemic inflammation and malnutrition are closely linked to frailty biology and contribute to catabolic stress, impaired recovery, and reduced tolerance of multimodal therapy. In HBP oncology, routinely available biomarkers such as C-reactive protein and albumin, and composite indices including the C-reactive protein-to-albumin ratio and the Geriatric Nutritional Risk Index, may capture inflammation-dominant and nutrition-dominant vulnerability that is often underrepresented by comorbidity-centered indices (33,66). Reports demonstrating prognostic value for combined inflammation and nutrition metrics after hepatectomy support their pragmatic role in risk characterization and pathway design (67). In hepatocellular carcinoma, findings linking preoperative hepatic immune status with prognosis further suggest that immune vulnerability may represent an important biological component within HBP onco-frailty (68). A practical direction is the biological enrichment of frailty assessment without disrupting workflow. The mFI incorporating albumin has been reported to improve risk stratification in HBP surgery, supporting the concept that adding biologic parameters can increase clinical relevance in tumor-driven stress states (69). At the same time, these markers are not disease-specific and should not be interpreted as mechanistic surrogates in isolation. Their main clinical value is to trigger targeted actions rather than to serve as labels. Examples include prioritizing biliary drainage and infection control when relevant, intensifying nutrition support, tailoring prehabilitation intensity, and planning treatment timing to preserve readiness for adjuvant therapy. Evidence supporting the feasibility of prehabilitation during neoadjuvant therapy in pancreatic cancer reinforces that such interventions can be incorporated into real-world pathways (70). Structural vulnerability, including skeletal fragility, may also carry oncologic implications after hepatectomy and warrants consideration when comprehensive physical resilience is being assessed (71). Reports demonstrating prognostic value for combined inflammation and nutrition metrics after pancreatic resection further support their role in risk characterization and perioperative pathway design (72,73).

Across studies, vulnerability in one or more domains of HBP onco-frailty has been associated with higher postoperative morbidity, delayed recovery, and reduced feasibility of systemic therapy, manifesting as delayed initiation and lower completion of perioperative or adjuvant chemotherapy. However, the strength of evidence varies by disease context, endpoint definition, and timing of assessment. Table 4 therefore should be understood as a pragmatic minimum viable workflow rather than a validated universal algorithm.

Molecular and microRNA insights

Evidence directly linking molecular signatures to perioperative decision-making in HBP surgery remains limited, and these findings should be positioned as hypothesis-generating. MicroRNAs related to muscle biology and inflammation, and proteomic signatures associated with future frailty, provide biologic plausibility for long-term vulnerability and potential avenues for refined stratification (74-79). Nevertheless, these markers are not yet ready for routine clinical integration in HBP pathways. At present, the most defensible strategy is staged implementation: perioperative assessment should be built on routine clinical domains first, with molecular layers added only when incremental value, feasibility, and reproducibility are demonstrated in HBP-specific prospective studies.

Limitations and implementation challenges

Frailty screening is not yet routine in HBP surgery. Major barriers include heterogeneity of instruments such as the Clinical Frailty Scale, the mFI, and the Liver Frailty Index, as well as the limited incorporation of inflammatory and nutritional biology in many commonly used indices (80,81). Biologically enriched approaches, including the mFI incorporating albumin and serum composites such as the C-reactive protein-to-albumin ratio and the Geriatric Nutritional Risk Index, may better reflect tumor-driven stress states and are attractive because they leverage routine testing (66,69,72,73). However, their incremental value over established surgical and organ-specific assessment tools remains insufficiently standardized across HBP settings.

Additional limitations arise from the evidence base itself. Much of the literature remains retrospective, often single-center, and heterogeneous with respect to disease mix, operative complexity, frailty definitions, measurement timing, and chosen outcomes. These factors complicate cross-study comparison and make it difficult to define universal thresholds for intervention. In addition, some frailty-related measures may capture transient disease-related deterioration rather than stable baseline vulnerability, which is clinically relevant but conceptually distinct.

Implementation barriers also include workflow constraints, variable clinician familiarity, and inconsistent access to performance-based assessment, which may be particularly relevant in routine surgical practice even when objective scales are available (82). Broader frailty consensus statements have emphasized the need for routine identification and structured management of frailty in clinical care (83). Society-level guidance increasingly supports perioperative optimization, enhanced recovery, and structured assessment of older or high-risk surgical patients, but direct guidance specifically focused on frailty assessment in HBP surgery remains limited. Current recommendations more often address broader perioperative care in older adults, ERAS pathways for liver surgery or transplantation, or liver disease-related frailty rather than a unified HBP-specific frailty standard (28-32).

Accordingly, priorities for the field include standardized operational definitions aligned with HBP-specific clinical contexts, prospective multicenter validation with calibration and clinical utility assessment, and workflow-oriented implementation studies that connect screening, targeted intervention, and outcome evaluation. In this sense, the next step is not merely better prediction, but a more explicit linkage between frailty-informed assessment and perioperative action.

Conclusions

Frailty in HBP surgery is commonly a disease- and treatment-modified vulnerability state shaped by cholestasis with jaundice, recurrent infection, tumor-associated inflammation, hepatic dysfunction, and operative stress. We propose HBP onco-frailty as a clinically operational construct that integrates four interacting domains: sarcopenia, malnutrition, impaired physical function, and systemic inflammation. Because widely used frailty instruments may under-capture inflammation- and nutrition-driven risk in HBP malignancies, stepwise biologic enrichment using routine biomarkers—such as C-reactive protein, albumin, the C-reactive protein-to-albumin ratio, and the Geriatric Nutritional Risk Index—may provide a pragmatic means of refining risk stratification while preserving workflow feasibility.

The intent of this framework is not labeling, but to trigger targeted optimization, including infection control, nutrition support, prehabilitation, and treatment-timing decisions that preserve recovery and readiness for multimodal therapy. At present, however, the evidence base remains heterogeneous, and no standardized HBP-specific operational definition has been established. Priorities for the field therefore include standardized operational definitions, multicenter prospective validation with calibration and clinical utility assessment, and implementation studies embedded within perioperative pathways.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0138/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0138/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0138/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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