Evidence summary: Prehabilitation strategies for patients with primary liver cancer

Abstract

Objective

To synthesise and appraise current evidence on prehabilitation strategies for patients with primary liver cancer.

Methods

Using the PIPOST framework, we formulated clinical questions and defined eligibility criteria. Guided by the “5S” evidence hierarchy, a comprehensive search was conducted across 20 sources—including clinical decision systems, guideline repositories, bibliographic databases, and professional society websites—from inception to 1 December 2024. Two independent reviewers screened and appraised eligible studies, and evidence synthesis was limited to those meeting predefined quality standards. Nine experts evaluated the evidence through a structured consensus process based on the FAME framework to determine recommendation grades.

Results

Twenty studies were included: 1 clinical decision tool, 5 guidelines, 5 systematic reviews, 5 expert consensuses, 3 evidence summaries, and 1 randomised controlled trial. A total of 36 evidence statements were extracted and categorised into six domains: prehabilitation candidates, timing of prehabilitation, nutritional optimisation, physical exercise, psychological support, and health education. Although part of the evidence originated from non-liver cancer populations, extrapolation was considered reasonable due to shared pathophysiological risks across major abdominal surgeries. Of these, 34 evidence statements received strong recommendations after expert appraisal.

Conclusions

This study consolidates practical, evidence-based prehabilitation strategies for patients with primary liver cancer, while underscoring the cautious use of extrapolated evidence where liver cancer-specific data are lacking. Despite methodological rigour, conclusions remain constrained by the limited availability of liver cancer-focused studies. Future research should generate direct evidence to refine prehabilitation protocols. Clinical application should integrate both the best available evidence and patient preferences.

Systematic review registration

Registered with the Fudan University Evidence-based Nursing Centre (ID: ES20246474).

Introduction

Primary liver cancer is the fourth most common malignant tumour and the second leading cause of cancer-related mortality in China.¹ Patients undergoing hepatopancreatobiliary surgery often exhibit chronic wasting, impaired nutritional intake, and digestive dysfunction.² Existing studies identify preoperative frailty and malnutrition as independent risk factors for adverse postoperative outcomes in liver cancer patients, including increased complication rates and reduced survival.^3,4 Notably, these conditions demonstrate significant overlap with sarcopenia in elderly populations,⁵ underscoring the clinical imperative for optimised preoperative management.

Prehabilitation, as an extension of the Enhanced Recovery After Surgery (ERAS), systematically targets modifiable preoperative risk factors to accelerate recovery.⁶ Its benefits have been established across multiple surgical disciplines, including cardiothoracic surgery, abdominal oncology,⁷ gynaecological oncology,⁸ and other cancer surgeries.⁹ Initially centred on cardiorespiratory conditioning through exercise training,¹⁰ contemporary prehabilitation programmes now incorporate nutritional support to mitigate malnutrition and weight loss in gastrointestinal cancer patients.^11,12 Emerging evidence further underscores its psychological benefits, such as enhanced treatment adherence and reduced preoperative anxiety, reinforcing the value of multimodal interventions.¹³ Accordingly, this study operationalises prehabilitation as a tripartite framework encompassing exercise, nutrition, and psychological support.¹⁴

Current prehabilitation protocols for liver cancer patients lack standardisation, frequently appearing as fragmented elements within broader perioperative guidelines.^11,15,16 This evidence-practice gap impedes the development of tailored preoperative strategies for this high-risk demographic. To address this, our study systematically evaluates existing prehabilitation evidence, with three principal objectives: (1) assessing the validity of extrapolating data from non-hepatic populations, (2) mitigating potential publication biases, and (3) formulating evidence-based clinical recommendations for implementation.

Methods

This study was conducted in accordance with the reporting standards of the Fudan University Evidence-based Nursing Centre, which were developed based on the JBI's methods of generating an evidence summary.^17,18

Problem establishment

The PIPOST model¹⁹ was used for problem establishment: P (population) was adults (≥ 18 years) undergoing surgery for primary liver cancer; I (intervention) was prehabilitation strategies; P (professionals) was healthcare providers; O (outcomes) was indicators related to improving perioperative outcomes; S (setting) was general surgery wards, outpatient clinics, or home-based environments; T (type of studies) was clinical decision tools, guidelines, expert consensuses, evidence summaries, systematic reviews, and randomised controlled trials.

Evidence retrieval

Guided by the “5S” pyramid model of evidence-based medicine,²⁰ we conducted a systematic search across the following sources: (1) Clinical decision tools: UpToDate, BMJ Best Practice; (2) Guideline repositories: National Institute for Health and Care Excellence (NICE), National Guidelines Clearinghouse (NGC), Evidence-Based Medicine Reviews (EBMR), Medlive, Guidelines International Network (GIN); (3) Databases: Joanna Briggs Institute (JBI), Cochrane Library, PubMed, Embase, Web of Science, BIOSIS Previews, CINAHL, Sinomed, China National Knowledge Infrastructure (CNKI), Wanfang Database; (4) Professional organisation websites: American Cancer Society (ACS), American Association for the Study of Liver Diseases (AASLD), Chinese Anti-Cancer Association (CACA), International Liver Cancer Association (ILCA). The search period spanned from database inception to 1 December 2024. A combination of Medical Subject Headings (MeSH) and free-text terms was used for database searches, while guideline repositories and organisational websites were queried using keyword searches. The PubMed search strategy is presented in Appendix A, with detailed search strategies and results provided in Appendix B.

Inclusion and exclusion criteria of evidence

Inclusion criteria: (1) study subjects were adult patients (≥ 18 years) undergoing surgical resection for primary liver cancer; (2) study content related to prehabilitation for liver cancer; (3) study types including clinical decision tools, evidence summaries, guidelines, expert consensus statements, systematic reviews, and randomised controlled trials (RCTs); (4) publications in Chinese or English.

Exclusion criteria: (1) represented duplicate publications or outdated versions; (2) guideline translations or secondary interpretive summaries without original content; (3) incomplete data or unavailable full text; (4) studies deemed low quality after critical appraisal.

Literature screening

All retrieved records were imported into NoteExpress software for automated duplicate removal, followed by manual verification. Two researchers trained in evidence-based methodology conducted title/abstract screening against eligibility criteria. Potentially eligible studies underwent full-text assessment by both reviewers to confirm inclusion. Discrepancies were resolved through discussion; persistent disagreements were adjudicated by a third senior investigator.

Quality evaluation of the literature

The quality of the literature was assessed using standardised tools: (1) Clinical decision tools were evaluated by source study verification. (2) Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ),²¹ with grading as follows: Grade A (direct recommendation, ≥ 60% score in all six domains), Grade B (modified recommendation, ≥ 3 domains scoring 30–59%) or Grade C (not recommended, ≥ 3 domains < 30%); (3) Evidence summaries were appraised using the Critical Appraisal for Summaries of Evidence (low quality: > 4 “No” responses); (4) Expert consensus statements, systematic reviews, and RCTs were evaluated using JBI critical appraisal tools.²² Low quality was defined as: > 4 “No” responses for systematic reviews/RCTs; > 2 “No” responses for expert consensus. Two trained researchers independently conducted assessments, with disagreements resolved by discussion with a third researcher.

Evidence level formation

Two researchers independently extracted and synthesized evidence, verified by a third reviewer. Conflicting evidence was prioritised according to the following criteria: (1) highest quality, (2) most recent publication date, and (3) domestic origin (Chinese studies). The JBI Levels of Evidence and Grades of Recommendation System (2014 edition)²³ was applied to rank the evidence from Level 1a (highest) to Level 5c (lowest).

Expert consensus and recommendation grading

Nine multidisciplinary experts (2 hepatobiliary surgeons, 1 anaesthetist, 1 rehabilitation therapist, 1 nutritionist, 1 evidence-based specialist, 3 oncology/hepatobiliary nurses; all with ≥ 10 years' experience) participated in a structured consensus process. Using the FAME framework (Feasibility, Appropriateness, Meaningfulness, Effectiveness),²² they pre-scored each item on a 5-point Likert scale (total score range: 4–20). Consensus required a coefficient of variation (CV) ​≤ ​0.25 with no major disciplinary dissent. Non-consensus items (CV ​> ​0.25) were systematically categorised as requiring either merging (conceptual overlap) or modification/deletion (contextual limitations), and resolved through a three-phase protocol: (1) review of the original evidence; (2) structured debate focusing on feasibility within resource constraints, physiological plausibility, conceptual fit within prehabilitation, and clarity of evidence formulation; (3) arbitration by an expert panel (e.g., requiring > 50% approval for deletions). Final recommendations were graded as: Grade A (strong recommendation, mean FAME score ≥ 16) or Grade B (weak recommendation, score < 16).

Results

Search results

A total of 3306 articles were retrieved. After screening, 20 articles were ultimately included. The literature screening process is presented in Fig. 1.

Fig. 1.

Flow diagram illustrating the original process of screening and identification of studies. JBI, Joanna Briggs Institute; CNKI, China National Knowledge Infrastructure; NICE, National Institute for Health and Care Excellence; NGC, National Guidelines Clearinghouse; EBMR, Evidence-Based Medicine Reviews; GIN, Guidelines International Network; ACS, American Cancer Society; AASLD, American Association for the Study of Liver Diseases; CACA, Chinese Anti-Cancer Association; ILCA, International Liver Cancer Association.

Characteristics of included studies

A total of 20 studies were included; see Table 1 for details. 70% (14/20) focused specifically on liver surgery populations^{15,16,27,30,31,}33, 34, 35, 36, 37, 38, 39, 40, 41, 25% (5/20) derived from general surgical/major abdominal surgery cohorts,24, 25, 26^,28,32 and 5% (1/20) derived from oncological surgical patients.²⁹

Table 1.

Characteristics of included studies (N ​= ​20).

Included literature	Type of literature	The literature theme
Fjoyce et al., 202424	Clinical decision tool	Overview of prehabilitation for surgical patients
Joliat et al., 202315	Guideline	Guidelines for perioperative care for liver surgery
Bloc et al., 202325	Guideline	Guidelines on perioperative optimisation protocol for the adult patient
Weimann et al., 202126	Guideline	ESPEN practical guideline: Clinical nutrition in surgery
Surgery & anesthesiology, 202127	Guideline	Clinical practice guidelines for ERAS in China: Hepatobiliary surgery
Tew et al., 201828	Guideline	Clinical guideline and recommendations on pre-operative exercise training in patients awaiting major non-cardiac surgery
Laza-Cagigas et al., 202429	Systematic review	Effect of prehabilitation programmes on functional capacity in patients awaiting oncological resections
Deprato et al., 202230	Systematic review	Surgical outcomes and quality of life following exercise-based prehabilitation for hepato-pancreatico-biliary surgery
Wong et al., 202031	Systematic review	Perioperative immunonutrition in hepatectomy
Heger et al., 202032	Systematic review	A systematic review and meta-analysis of physical exercise prehabilitation in major abdominal surgery
McKay et al., 201933	Systematic review	Pre-operative vs. Peri-Operative nutrition supplementation in hepatic resection for cancer
Chen et al., 202234	Expert consensus	Hunan expert consensus on clinical pathway for enhanced recovery after surgery of hepatopancreatobiliary surgical diseases
CROSS-STRAITS MEDICINE EXCHANGE ASSOCIATION, 202135	Expert consensus	Chinese expert consensus on the peri-operative management of hepatectomy for liver cancer
Jia et al., 201736	Expert consensus	Chinese expert consensus on enhanced recovery after hepatectomy
Liu et al., 201737	Expert consensus	Chinese expert consensus on enhanced recovery after surgery for Laparoscopic hepatectomy
Specialty committee of hepatobiliary and pancreatic surgery, 201638	Expert consensus	Expert consensus on enhanced recovery after surgery for hepatobiliary and pancreatic surgery
Yan et al., 202416	Evidence summary	Best evidence of perioperative exercise interventions in patients with liver cancer
Ren et al., 202239	Evidence summary	A summary of the best evidence for perioperative nutritional support in patients after open abdominal hepatectomy
Wang et al., 202240	Evidence summary	Best evidence summary of perioperative nutritional management in patients undergoing hepatectomy
Russell et al., 201941	RCT	Preoperative immunonutrition in patients undergoing liver resection: A prospective randomised trial

ERAS, Enhanced Recovery After Surgery; RCT, randomised controlled trial.

Quality evaluation results of the included studies

Quality evaluation results of clinical decision tool

One clinical decision tool²⁴ from UpToDate was included. It was classified as high-quality evidence and directly adopted.

Quality evaluation results of guidelines

Five guidelines^15,25, 26, 27, 28 demonstrated excellent inter-rater reliability (ICC ​= ​0.949). As shown in Table 2, two guidelines^15,26 achieved Grade A recommendations, while three^25,27,28 received Grade B.

Table 2.

Quality evaluation results of included guidelines (N ​= ​5).

Included Guidelines	Field scoresa in various domains (%)						≥ 60%	≥ 30%	< 30%	Recommendation level
	Scope and purpose	Stakeholder involvement	Rigour of development	Clarity of presentation	Applicability	Editorial independence
Joliat et al., 202315	90.28	68.06	87.50	66.67	54.17	95.83	6	6	0	A
Bloc et al., 202325	94.44	76.39	81.02	57.29	56.25	100.00	4	6	0	B
Weimann et al., 202126	95.83	77.78	85.65	70.83	58.33	95.83	6	6	0	A
Surgery & anesthesiology 202127	98.61	75.00	84.26	62.50	45.83	89.58	5	6	0	B
Tew et al., 201828	94.44	73.61	84.72	63.54	77.08	47.92	5	6	0	B

^a$\text{Field}\text{Score}=\frac{\text{Actual}\text{Score}-\text{Minimum}\text{Possible}\text{Score}}{\text{Maximum}\text{Possible}\text{Score}-\text{Minimum}\text{Possible}\text{Score}}\times 100\%$⁴².

Quality evaluation results of systematic reviews

Five systematic reviews29, 30, 31, 32, 33 were included. The quality assessment results are presented in Table 3.

Table 3.

Quality evaluation results of included systematic reviews (N ​= ​5).

Included systematic reviews	①	②	③	④	⑤	⑥	⑦	⑧	⑨	⑩	⑪
Laza-Cagigas et al., 202429	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Deprato et al., 202230	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Unclear	Yes	Yes
Wong et al., 202031	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Heger et al., 202032	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
McKay et al., 201933	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes

① Is the review question clearly and explicitly stated? ② Were the inclusion criteria appropriate for the review question? ③ Was the search strategy appropriate? ④ Were the sources and resources used to search for studies adequate? ⑤ Were the criteria for appraising studies appropriate? ⑥ Was critical appraisal conducted by two or more reviewers independently? ⑦ Were there methods to minimize errors in data extraction? ⑧ Were the methods used to combine studies appropriate? ⑨ Was the likelihood of publication bias assessed? ⑩ Were recommendations for policy and/or practice supported by the reported data? ⑪ Were the specific directives for new research appropriate?

Quality evaluation results of expert consensus

Five expert consensus statements34, 35, 36, 37, 38 were included. The quality assessment results are presented in Table 4.

Table 4.

Quality evaluation results of included expert consensus (N ​= ​5).

Included expert consensus	①	②	③	④	⑤	⑥
Chen et al., 202234	Yes	Yes	Yes	Yes	Yes	Unclear
CROSS-STRAITS MEDICINE EXCHANGE ASSOCIATION, 202135	Yes	Yes	Yes	Yes	Yes	Unclear
Jia et al., 201736	Yes	Yes	Yes	Yes	Yes	Unclear
Liu et al., 201737	Yes	Yes	Yes	Yes	Yes	Unclear
Specialty committee of hepatobiliary and pancreatic surgery 201638	Yes	Yes	Yes	Yes	Yes	Unclear

① Is the source of the opinion clearly identified? ② Does the source of opinion have standing in the field of expertise? ③ Are the interests of the relevant population the central focus of the opinion? ④ Is the stated position the result of an analytical process, and is there logic in the opinion expressed? ⑤ Is there reference to the extant literature? ⑥ Is any incongruence with the literature/sources logically defended?

Quality evaluation results of evidence summaries

Three evidence summaries^16,39,40 were included. The quality assessment results are presented in Table 5.

Table 5.

Quality evaluation results of included evidence summaries (N ​= ​3).

Included evidence summaries	Summary topic	Summary methods				Summary content				Summary application
	①	②	③	④	⑤	⑥	⑦	⑧	⑨	⑩
Yan et al., 202416	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Ren et al., 202239	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes
Wang et al., 202240	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes

① Is the summary specific in scope and application? ② Is the authorship of the summary transparent? ③ Are the reviewer(s)/editor(s) of the summary transparent? ④ Are the search methods transparent and comprehensive? ⑤ Is the evidence grading system transparent and translatable? ⑥ Are the recommendations clear? ⑦Are the recommendations appropriately cited? ⑧ Are the recommendations current? ⑨ Is the summary unbiased? ⑩ Can this summary be applied to your patients?

Quality evaluation results of randomised controlled trials

One RCT⁴¹ was included. The quality assessment results are presented in Table 6.

Table 6.

Quality evaluation results of included randomised controlled trial (N ​= ​1).

Included RCT	①	②	③	④	⑤	⑥	⑦	⑧	⑨	⑩	⑪	⑫	⑬
Russell et al., 201941	Yes	Yes	Yes	No	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes

① Was true randomization used for assignment of participants to treatment groups? ② Was allocation to treatment groups concealed? ③ Were treatment groups similar at baseline? ④ Were participants blind to treatment assignment? ⑤ Were those delivering treatment blind to treatment assignment? ⑥ Were outcomes assessors blind to treatment assignment? ⑦ Were treatment groups treated identically other than the intervention of interest? ⑧ Was follow-up complete, and if not, were differences between groups in terms of their follow-up adequately described and analyzed? ⑨ Were participants analyzed in the groups to which they were randomised? ⑩ Were outcomes measured in the same way for treatment groups? ⑪ Were outcomes measured in a reliable way? ⑫ Was appropriate statistical analysis used? ⑬ Was the trial design appropriate, and any deviations from the standard RCT design (individual randomization, parallel groups) accounted for in the conduct and analysis of the trial? RCT, randomised controlled trial.

Summary and description of evidence

Through systematic extraction and synthesis, we developed 36 evidence-based recommendations across six prehabilitation domains (Table 7). The FAME scoring methodology and consensus process are detailed in Appendix C.

Table 7.

Summary of the evidence on prehabilitation strategies for liver cancer patients.

Category		Content of evidence	Level	Recommendation
Prehabilitation candidates		1. For high-risk liver cancer patients (e.g., older age, frailty, malnutrition, overweight, smoking or emotional disorders),15,24 a multidisciplinary preoperative assessment25 and multimodal prehabilitation plan are recommended.15,24,27,29,30,32,34	1b	A
Timing of prehabilitation		2. A duration of 2–6 weeks15,16,24 is recommended to undergo prehabilitation and this can be individualised based on the patient's diagnosis and surgery urgency.24	5a	A
Nutritional optimisation	Nutritional goals	3. The perioperative nutritional goals in liver cancer patients targets are: 25–30 kcal/(kg·d) for energy and 1.2–2.0 g/(kg·d) for protein.40	5b	A
	Nutritional screening	4. For patients undergoing elective liver cancer surgery, nutritional screening should be conducted.40	5b	A
		5. It is recommended to use the nutritional risk screening 2002 (NRS 2002) for nutritional risk assessment24,35, 36, 37,40.	5a	A
	Nutritional sssessment	6. For patients with nutritional risk, further nutritional status assessment should be conducted using the subjective global assessment (SGA)24,40 or the patient-generated subjective global assessment (PG-SGA).35,40	5b	A
	Nutritional intervention	7. All patients should receive oral protein supplementation for 5–7 days before surgery.24	5a	A
		8. It is recommended to establish a standard procedure for nutritional support26 and to develop individualised plans for patients with identified nutritional risks (NRS 2002 score ≥ 3)26,36, 37, 38.	5a	A
		9. For patients with no-to-moderate nutritional risk (NRS 2002 score 0–4), oral nutritional supplements (ONS)36,39,40 providing 400–900 kcal/day are recommended to meet energy needs.40	5a	A
		10. When any of the following high nutritional risk conditions are present, it is recommended to initiate nutritional therapy at least 7–14 days before surgery:15,26,34,35,39 ① BMI < 18.5 or < 20 if aged > 65 years; ② unplanned weight loss > 10% within the past 6 months; ③ food intake < 50% of normal in the past week; ④ NRS 2002 score ≥ 5 or SGA grade C; ⑤ serum albumin level < 3.0 g/dL in the absence of hepatic or renal dysfunction.	3b	A
		11. Nutritional support should prioritise the enteral route. If intake is less than 60% of the target energy and protein requirement, parenteral nutrition support should be combined.26,34,38,40	1b	A
		12. Current evidence does not support routine preoperative immunonutrition for liver cancer patients.15,31,37,41	1b	B
Physical exercise	Exercise evaluation	13. A comprehensive preoperative evaluation should include both activity tolerance assessment and routine medical examination prior to initiating exercise interventions.16,27	5b	A
		14. It is recommended to use the eastern cooperative oncology group performance status (ECOG PS) score for a simple and effective assessment of patients' functional status.35	5b	A
		15. Recommended objective functional assessments include: ① physical performance tests: gait speed, 5-repetition chair stand test; ② strength measures: dominant hand grip strength, quadriceps muscle thickness; ③ cardiorespiratory tests: 6-min walk test (6MWT), stair climb test, shuttle walk test; ④ advanced testing: cardiopulmonary exercise testing when available.16,24,28,34	5b	A
	Exercise intervention	16. Exercise prescriptions should be developed based on baseline fitness level from evaluation results, patient preferences and capabilities.16,28	5b	A
		17. Preoperative exercise training is strongly recommended for patients with any of these risk factors:24,28 ① age > 70 years; ② frailty; ③ poorly controlled chronic illnesses e.g., diabetes or hypertension; ④ preoperative chemotherapy or radiation therapy; ⑤ inactivity by the WHO standard < 150 minutes of moderate intensity exercise or < 75 minutes of vigorous intensity exercise per week.	5b	A
		18. Preoperative exercise for major abdominal surgery includes aerobic exercise e.g., walking, jogging, brisk walking, resistance training e.g., exercises using elastic resistance bands, resistance equipment or bodyweight-based functional activities and cardiopulmonary training e.g., deep breathing, diaphragmatic breathing, pursed-lip breathing, effective coughing and inspiratory muscle training.16,24	1a	A
		19. Recommended frequency: aerobic exercise 3–5 times/week, resistance training 2–3 times/week and cardiopulmonary training 3–5 times/week.16,28	2b	A
		20. Recommended intensity: moderate 40–59% VO2R or HRR, or 55–69% of HRmax, or Borg PRE rating of 12–13 or lower for aerobic and resistance exercises.16,28	2b	A
		21. Recommended duration: aerobic exercise 15–60 minutes, resistance training 20–40 minutes, 8–10 muscle groups, 8–12 reps/set, 2–4 sets and cardiopulmonary training 10–15 minutes.16,28	2b	A
	Exercise monitoring	22. Immediate cessation criteria during exercise16: ① blood oxygen saturation below 90%, heart rate exceeding the target heart rate; ② patients exhibiting orthostatic intolerance or reporting symptoms such as discomfort or dizziness.	1a	A
		23. Smart devices like bracelets are recommended to monitor patients' activity, steps, heart rate and sleep.16	1b	A
		24. Supervised exercise, including guided sessions, phone follow-ups, diaries and home supervision, is recommended to improve adherence.16	1b	A
		25. Exercise intensity can be assessed using heart rate reserve (HRR), maximum heart rate (HRmax) or the Borg rating of perceived exertion scale (Borg RPE).16,28	1b	A
Psychological support	Psychological assessment	26. It is recommended that all patients undergo psychological screening before surgery.24	5a	A
		27. It is recommended to use the hospital anxiety and depression scale (HADS) for psychological assessment of patients.27,34	5a	A
	Psychological intervention	28. Targeted behavioral interventions are recommended to reduce preoperative stress and anxiety, including progressive muscle relaxation techniques, cognitive behavioral therapy (CBT), virtual reality experiences, guided imagery, deep breathing and mindful meditation.24	1a	A
		29. In rare cases, counselling or specialist psychological or psychiatric care may be necessary for a patient with severe anxiety or depression.24	5b	A
Health education	Preoperative education	30. A multimodal education program should be delivered, covering: Individualised surgical/anesthesia procedures including ERAS protocols, prehabilitation components and postoperative recovery expectations.15,24,34,36, 37, 38, 39	5b	A
	Education format	31. It is recommended to use diverse educational formats such as brochures, multimedia materials and simulation-based training.15,34,39	5b	A
	Education timing	32. Patient education should span from the pre-admission phase to post-discharge follow-up.16,27,34,36,38	3b	A
	Smoking and alcohol cessation	33. It is recommended to cease smoking and alcohol consumption for 4–8 weeks before surgery.15,24,26,36	1a	A
	Preoperative gastrointestinal preparation	34. Mechanical bowel preparation is not recommended for liver cancer patients.27,34, 35, 36, 37, 38,40	1a	A
	Oral carbohydrate treatment	35. It is recommended that patients drink 800 mL of a 12.5% carbohydrate beverage the night before surgery15,26,40 or 10 hours27,32 before surgery, followed by ​≤ ​400 mL within 2 hours before surgery,25, 26, 27,39,40 adjusting based on the patient's tolerance and comfort, while diabetic patients should substitute water for the beverage.34	5b	B
	Preoperative fasting and fluid restriction	36. Solid starchy foods may be consumed up to 6 hours before surgery including milk,15,25, 26, 27,34,36, 37, 38, 39, 40 and clear fluid beverages may be ingested up to 2 hours before surgery excluding alcohol15,25, 26, 27,34,36,38, 39, 40—except for patients with delayed gastric emptying, abnormal gastrointestinal motility, diabetes, or those undergoing emergency surgery.27,34,35,40	5b	A

WHO, World Health Organisation; Borg RPE, Borg Rating of Perceived Exertion scale, moderate intensity ​= ​12–13 “somewhat hard”; Peak oxygen uptake reserve, VO₂R ​= ​Difference between the rate of oxygen consumption at rest and at maximal exercise, moderate intensity ​= ​40% to 59% VO₂R; Heart rate reserve, HRR ​= ​Difference between resting and maximal heart rate, moderate intensity ​= ​40% to 59% HRR; Maximum heart rate, HRmax ​= ​220-age (beats per minute), moderate intensity ​= ​55% to 69% HRmax.

Discussion

This evidence synthesis reveals both the potential and challenges in implementing prehabilitation for primary liver cancer patients. While only 10% (2/20) of included studies specifically addressed hepatic malignancies,^16,35 we carefully extrapolated evidence from general surgical and oncologic studies based on shared pathophysiological mechanisms, comparable surgical stress responses, and hepatobiliary specialist consensus regarding clinical applicability. This approach aligns with recent systematic reviews demonstrating transferable benefits of prehabilitation across gastrointestinal malignancies.²⁹

Identifying prehabilitation candidates and timing: a core prerequisite

Evidence 1–2 highlights the target population and timing for prehabilitation. Liver cancer patients present unique disease-specific characteristics that amplify prehabilitation importance, including cirrhosis-associated liver dysfunction,⁴⁰ accelerated muscle catabolism, and metabolic disturbances (such as insulin resistance in non-alcoholic steatohepatitis^26,43). These factors, compounded by frailty, malnutrition or advanced age (≥ 65 years), substantially increase postoperative risks,^24,25,44 making early identification via preoperative assessments critical.

However, implementing this core prerequisite remains challenging. A major feasibility barrier is the integration of systematic risk stratification into busy preoperative clinics, which demands dedicated personnel, time, and structured workflows to ensure timely identification and referral of high-risk patients. Another challenge involves determining the optimal prehabilitation duration. Current guidelines recommend a minimum 4-week intervention window,^15,24 yet pragmatic adaptations are frequently required owing to tumour dynamics and the exigencies of surgical scheduling. For instance, one study suggests 2–4 weeks of preoperative exercise in Chinese clinical practice,¹⁶ leading to expert consensus on a 2–6 week window. This adaptability facilitates risk stratification, phased interventions, and individual adjustments, aligning with ERAS principles. A flexible timeframe promotes the development of evidence-based and feasible protocols suitable for diverse healthcare settings.

Personalised nutritional interventions: the driver of prehabilitation

Evidence 3–12 collectively establishes a nutritional support framework for prehabilitation in liver cancer. Impaired hepatic protein synthesis and hypermetabolism predispose patients to sarcopenia,²⁶ while complications such as ascites and varices further limit oral intake.⁴⁰ This pathophysiology explains the documented 57.8% prevalence of moderate-to-severe malnutrition among Chinese liver cancer populations.⁴⁵ Universal screening using validated tools (e.g., NRS 2002) remains essential, with particular emphasis on high-risk patients (NRS 2002 ​≥ ​5) who derive significant complication reduction from targeted nutritional support.²⁶

Current evidence supports a perioperative protein intake of 1.2–2.0 g/(kg·d) and an energy intake of 25–30 kcal/(kg·d) for patients undergoing hepatectomy,⁴⁰ reflecting the increased protein requirements associated with liver dysfunction and surgical stress. For patients failing to meet requirements through enteral routes, supplemental parenteral nutrition demonstrates efficacy in improving postoperative outcomes.^26,39,40 However, practical implementation of nutritional support faces challenges, including limited dietitian availability and socioeconomic barriers that affect dietary adherence. Nursing teams play a crucial role through patient education, motivational support, and early detection of compliance issues using simple monitoring tools. Additionally, preoperative implementation of a hypocaloric, reduced-fat diet in obese patients may decrease intraoperative blood loss during hepatectomy,⁴⁶ underscoring the necessity of metabolic individualisation in nutritional planning.

Regarding immunonutrition, while general surgical populations may benefit from preoperative immunomodulatory nutrition,²⁴ liver-specific evidence remains limited. Only one RCT evaluating immunonutrition before hepatectomy reported no benefit in well-nourished patients.⁴¹ Similarly, perioperative omega-3 fatty acids have shown no protective effect in liver surgery populations.⁴⁷ Current guidelines, including those from ESPEN²⁶ and ERAS protocols,¹⁵ discourage routine immunonutrition, reserving it for specific nutritional deficiencies. This aligns with a systematic review prioritising parenteral over enteral immunonutrition in selected hepatectomy cases.³¹ Given the heterogeneity in response to nutritional interventions and the complexity of liver disease, we advocate cautious extrapolation from non-hepatic evidence while accounting for publication bias through inclusion of negative trials.

In ideal settings, a multidisciplinary approach with dedicated dietitian support should be pursued. In constrained environments, efforts should focus on universal screening, prioritizing high-risk patients and educating them on affordable protein-rich foods. The use of cost-effective ONS can be a first-line strategy before considering parenteral options. Future research should include liver cancer-specific trials and implementation studies to develop effective and scalable nutrition strategies across diverse healthcare systems.

Targeted exercise training: the pillar of prehabilitation

Evidence 14–25 describes the implementation framework of preoperative exercise training within liver cancer prehabilitation. Accumulating evidence supports that structured preoperative exercise training serves as a fundamental component of prehabilitation, offering three well-established benefits: improved physical function, enhanced postoperative recovery trajectories, and reduced complication rates.^24,48 These advantages have been documented across both general oncological populations⁴⁸ and patients undergoing hepatobiliary surgeries.^29,30,32,34 When implementing such programs, clinicians must select assessment tools that balance clinical practicality with prognostic value. Cardiopulmonary exercise testing (CPET) provides comprehensive metabolic evaluation but remains resource-intensive and limited to specialised centres,⁴⁴ whereas the 6-min walk test (6MWT) offers clinically meaningful assessment of functional reserve,¹⁵ with predictive value for post-hepatectomy outcomes.^7,48

The core implementation challenge is designing a feasible and tolerable exercise regimen. The high prevalence of frailty (35%)⁴⁹ and sarcopenia (41.7%)⁵⁰ in liver cancer patients underscores the importance of thorough baseline assessments incorporating both performance-based measures and strength evaluations. These considerations, combined with severe cancer-related fatigue commonly reported by patients,⁵¹ require modification to standard exercise recommendations.⁴³ While general guidelines recommend moderate-to-vigorous intensity exercise for patients undergoing major abdominal surgery,²⁸ emerging evidence specific to liver cancer populations supports the adaptation to lower-to-moderate intensity.¹⁶ Clinical observations suggest that liver cancer patients gravitate toward sustained light exercise, which appears better tolerated while still providing functional benefits.⁵¹ Therefore, consistent participation at manageable intensities should be prioritized over ideal but potentially unattainable targets.

Furthermore, the implementation of exercise requires attention to patient adherence challenges.^24,28 Successful programs incorporate patient-centred design principles that accommodate individual preferences and treatment schedules, supported by monitoring systems ranging from wearable technology to structured performance documentation. Regular follow-up and active caregiver engagement further enhance effectiveness.⁴³ Given practical constraints such as limited equipment, space, and professional supervision, hybrid or home-based exercise models are recommended. Future research should prioritise establishing optimal intensity thresholds and validating standardised outcome measures specific to this population, particularly regarding the impact of different exercise regimens on postoperative recovery trajectories.

Positive psychology: the emotional pillar of prehabilitation

Evidence 26–29 underscores the importance of psychological assessment and intervention. The bidirectional relationship between psychological distress and physiological dysfunction creates a compelling rationale for routine psychological screening in this patient population.^52,53 Current evidence confirms that psychological distress triggers measurable physiological changes, including elevated cortisol levels, immune suppression, and increased inflammatory markers—all of which may adversely affect surgical recovery and increase neurocognitive risks.^54,55

However, the integration of psychosocial care faces significant barriers, including stigma, resource scarcity, and workflow constraints. A stepped-care approach is therefore recommended, beginning with basic emotional support and counselling provided by nurses, followed by specialist referral for severe cases. Nurses are particularly well-positioned for this role, as their frequent patient interactions enable early distress detection and delivery of simple but effective interventions like relaxation techniques and procedural education.^56,57 For patients requiring advanced support, evidence-based therapies such as CBT and MBSR²⁴ should be offered, potentially through digital health platforms, group sessions or individual therapy.

Implementing routine psychological screening and tiered interventions requires careful integration into clinical workflows, addressing challenges such as time constraints, provider training, and reimbursement. Future efforts should focus on the development of efficient and scalable psychosocial support models that maintain patient-centred care even in resource-limited settings.

Health education: the foundation of prehabilitation

Evidence 30–36 underscores the importance of health education. Targeted lifestyle modification counseling addressing smoking cessation and alcohol abstinence reduces postoperative pulmonary complications and surgical site infections^58,59 when initiated 2–4 weeks preoperatively.^15,24 Therefore, healthcare providers should proactively communicate the importance of cessation and its benefits for surgical outcomes. Evidence-based nutritional education, particularly regarding preoperative carbohydrate loading, has been shown to mitigate postoperative insulin resistance, reduce hospital stay duration, and decrease nausea/vomiting incidence.^26,60

The efficacy of these educational interventions is significantly enhanced by employing multimodal delivery methods combining verbal instruction, written materials, and digital resources.¹⁵ Such diversification accommodates varying learning preferences and improves retention of complex medical information.

Importantly, involving family members in the educational process enhances long-term compliance with prehabilitation protocols,^15,24 leveraging social support mechanisms to reinforce behavioural changes. This approach is particularly valuable in cultural contexts where family involvement in healthcare decisions is prominent, though it requires sensitivity to family dynamics to avoid placing undue pressure on patients.

Successful integration of health education into prehabilitation requires clear communication, accessible resources, and thoughtful family engagement. Without systematic implementation, even well-founded educational strategies may be overlooked in busy clinical settings. Future quality improvement initiatives should evaluate the effect of different educational approaches on patient behaviour and outcomes.

The conceptual model of prehabilitation in liver cancer patients

Fig. 2 presents our evidence-based conceptual model for liver cancer prehabilitation, adapted from Tew et al.'s framework.²⁸ The model's design reflects the contemporary understanding that optimal prehabilitation extends beyond the preoperative period to encompass the entire surgical journey.

Fig. 2.

The conceptual model of prehabilitation in liver cancer patients. All patients experience an acute decline in function after surgery, followed by a recovery phase (A). Patients with low physiological reserve or high risk factors may face higher complication rates and slower recovery, sometimes leading to incomplete recovery (B). A prehabilitated patient may have greater physiological reserve at the time of surgery, enabling a faster recovery (C). Prehabilitated patients may be better able to retain long-term functional capacity in complicated cases (D).

Limitations

Several methodological considerations should be acknowledged when interpreting these findings. First, the exclusion of non-Chinese/English studies may have omitted relevant evidence. Second, the current evidence base necessitated careful extrapolation from related surgical populations, which may not fully account for the unique metabolic considerations in liver cancer. Finally, the included studies reflect diverse healthcare systems, suggesting that local adaptation of these recommendations may be required to account for variations in clinical practice and resource availability. These limitations highlight valuable directions for future research to strengthen the evidence base.

Conclusions

This study consolidates 36 actionable prehabilitation strategies for primary liver cancer, addressing 6 key domains: prehabilitation candidates, timing of prehabilitation, nutritional optimisation, physical exercise, psychological support, and health education. This framework provides a foundation for optimising surgical outcomes while highlighting the need for cautious application of indirect evidence where liver cancer-specific data are lacking. Recommendations should be implemented judiciously, with adaptation to local clinical contexts, resource availability, and patient preferences.

CRediT authorship contribution statement

Tu Jinyi: Conceptualisation, Data curation, Validation, Software, Writing – original draft, Funding acquisition, Formal analysis. Shen Yan: Conceptualisation, Visualization, Investigation, Writing – original draft, Formal analysis. Chen Yun: Data curation, Formal analysis, Visualization, Resources. Zhang Yanshan: Data curation, Formal analysis, Validation, Software. Zhou Sijia: Formal analysis, Visualization, Validation. Luo Weixiang: Investigation, Supervision, Resources, Writing – review & editing. Zhang Haiyan: Project administration, Writing – review & editing, Funding acquisition. All authors have read and approved the final manuscript.

Ethics statement

Not required.

Data availability statement

The data that support the findings of this study are openly available in Fudan University Centre for the Evidence-based Nursing at http://ebn.nursing.fudan.edu.cn, reference number ES20246474.

Declaration of generative AI and AI-assisted technologies in the writing process

No AI tools/services were used during the preparation of this work.

Funding

This work was supported by the Shenzhen Science and Technology Program (Grant No. JCYJ20240813104259049). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

Declaration of competing interest

The authors declare no conflict of interest.

Supplementary data

The following are the Supplementary data to this article: