Major hepatobiliary (HPB) surgery is associated with high physiological stress, significant metabolic demand, and substantial risk of postoperative morbidity. Preoperative nutritional status is a critical determinant of surgical outcomes, influencing immune competence, wound healing, and organ function. Malnutrition, sarcopenia, and inflammatory dysregulation are prevalent even among patients without overt weight loss, making early detection and targeted intervention essential [1,2].

Walcott-Sapp and Billingsley (2018) emphasized that comprehensive preoperative optimization, including nutrition-focused strategies, can improve recovery and reduce complications following major hepatic resection [1]. A systematic review by Liu and Xue (2015) concluded that perioperative nutritional support is associated with reduced postoperative complications, particularly infections and length of stay, in hepatobiliary surgery [2]. Evans et al. (2014) further highlighted that proactive nutritional optimization—when combined with functional and metabolic conditioning—can modify surgical risk in high-demand operations [3].

Recent data suggest that prehabilitation programs integrating nutrition, exercise, and patient education may yield additive benefits. Wang et al. (2020) reported that such interventions before elective liver resection improved functional capacity, reduced length of stay, and enhanced patient-reported recovery [4]. Similarly, Toh et al. (2024) noted that prehabilitation in liver surgery is associated with improved postoperative trajectories, especially when nutrition is individualized [5]. Wu et al. (2025) reinforced that perioperative nutrition management in hepatobiliary tumour surgery should be tailored to biochemical, anthropometric, and inflammatory parameters to optimize clinical benefit [6].

Despite this growing evidence base, there is limited prospective data from Indian tertiary centres assessing the effect of structured preoperative nutritional optimization—including biochemical, functional, and inflammatory targets—on postoperative morbidity in major HPB surgery. This study was designed to address this gap.

Objectives

1. To evaluate the impact of structured preoperative nutritional optimization on major postoperative morbidity in patients undergoing major hepatobiliary surgery.
2. To assess changes in biochemical, anthropometric, and functional nutritional parameters following optimization.
3. To identify independent predictors of major postoperative morbidity using multivariate analysis.

Study design and setting

A prospective interventional study was conducted in the Department of HPB Surgery, SMS Medical College and Attached Hospitals, Jaipur, from March 2022 to February 2024. Consecutive adult patients scheduled for elective major hepatobiliary surgery were enrolled.

Eligibility criteria

Inclusion criteria:

• Age ≥ 18 years
• Scheduled for major liver, biliary, or combined hepatopancreatobiliary resections
• Anticipated surgery ≥ 7 days after initial assessment

Exclusion criteria:

• Emergency surgery
• Severe hepatic decompensation (Child–Pugh C) or multi-organ failure
• Inability to participate in functional assessment (neuromuscular limitations)
• Refusal to consent

Baseline assessment

All patients underwent comprehensive nutritional and functional assessment, including:

• Biochemical: serum albumin, prealbumin, C-reactive protein (CRP)
• Anthropometric: BMI, skeletal muscle index (computed tomography–based)
• Functional: handgrip strength (Jamar dynamometer)
• Subjective: Subjective Global Assessment (SGA)
• Nutritional screening: NRS-2002 score

Optimization protocol

Patients with deficits in any biochemical, anthropometric, or functional domain were enrolled in a structured nutritional optimization program, tailored according to individual needs:

• Oral diet modification (protein-rich, calorie-targeted)
• Oral nutritional supplements (high-protein, omega-3 enriched)
• Enteral nutrition via nasogastric or nasojejunal feeding when oral intake was inadequate
• Parenteral nutrition in select cases with contraindications to enteral feeding
• Immunonutrition in patients with elevated inflammatory markers or high surgical stress risk

Optimization duration continued until predefined nutritional targets were met or until the earliest of: (a) planned surgical date, or (b) maximum 21 days of intervention.

Definition of optimization achieved

Optimization was considered achieved if at least two of the following were met:

• Increase in serum albumin by ≥ 0.3 g/dL or normalization (>3.5 g/dL)
• Increase in prealbumin by ≥ 2 mg/dL
• Reduction in CRP by ≥ 2 mg/L
• Increase in skeletal muscle index by ≥ 0.5 cm²/m²
• Increase in handgrip strength by ≥ 1 kg

Perioperative care and outcome assessment

Surgical and anaesthetic protocols were standardized across the cohort. Postoperative morbidity was recorded and graded according to the Clavien–Dindo classification, with major morbidity defined as grade III or higher. Complication-specific outcomes included surgical site infection, pneumonia, bile leak, acute kidney injury, post-hepatectomy liver failure, and other systemic events. Secondary outcomes included length of hospital stay (LOS), ICU admissions, readmissions within 30 days, and 30-day mortality.

Statistical analysis

Continuous variables were expressed as mean ± SD or median [IQR], and categorical variables as frequencies and percentages. Between-group comparisons were performed using Student’s t-test or Mann–Whitney U test for continuous data, and chi-square or Fisher’s exact test for categorical data. Logistic regression was used to identify independent predictors of major morbidity. Statistical significance was set at p < 0.05. Analyses were conducted using SPSS v26.

Study Cohort and Baseline Characteristics

Between March 2022 and February 2024, a total of 100 patients undergoing major hepatobiliary surgery were enrolled in this prospective interventional study. The mean age was 53.3 ± 10.9 years, and two-thirds of the cohort were male (67%). Most patients were classified as ASA III (53%), with ASA II (35%) and ASA IV (12%) less frequent. Diabetes mellitus was present in 32%, while 25% had underlying cirrhosis.

The most common operative procedure was major hepatectomy (36%), followed by Whipple procedure (30%), minor hepatectomy (24%), and biliary reconstruction (10%).

Baseline nutritional assessment revealed a mean BMI of 23.1 ± 2.8 kg/m². The mean serum albumin and prealbumin levels were 3.0 ± 0.5 g/dL and 15.2 ± 3.8 mg/dL, respectively, with a mean CRP of 25.4 ± 9.8 mg/L. The median NRS-2002 score was elevated (mean 3.9 ± 1.0), and 70% of patients were graded as SGA B or C, indicating moderate to severe malnutrition. Handgrip strength averaged 21.9 ± 5.3 kg, while the mean skeletal muscle index (L3 SMI) was 40.3 ± 5.1 cm²/m². Mean phase angle was 4.5 ± 0.8°, vitamin D concentration 20.4 ± 8.2 ng/mL, and hemoglobin 12.0 ± 1.4 g/dL.

Table 1. Baseline characteristics of the study cohort (N = 100)

Values are presented as mean ± SD or n (%). ASA = American Society of Anesthesiologists; BMI = body mass index; CRP = C-reactive protein; NRS = Nutritional Risk Screening; SGA = Subjective Global Assessment; SMI = skeletal muscle index.

2. Preoperative Nutritional Optimization Process

All patients underwent a structured preoperative optimization protocol. The median duration of optimization was 12 days [IQR 8–16]. Nutrition was delivered via oral diet (52%), oral nutritional supplements (32%), enteral feeding (13%), and parenteral nutrition (3%). Immunonutrition was used in 60% of patients. Based on predefined composite criteria, optimization was achieved in 68% of the cohort.

Paired analyses demonstrated clinically and statistically significant improvements across key parameters. Serum albumin increased by +0.49 g/dL (95% CI, +0.42 to +0.56; p < 0.0001) and prealbumin by +3.02 mg/dL (95% CI, +2.84 to +3.20; p < 0.0001). CRP decreased by −4.96 mg/L (95% CI, −5.61 to −4.31; p < 0.0001). Functional and body composition indices also improved: handgrip strength increased by +2.01 kg (95% CI, +1.81 to +2.20; p < 0.0001) and L3 skeletal muscle index by +1.01 cm²/m² (95% CI, +0.92 to +1.10; p < 0.0001) (Table 2).

These changes are consistent with goal-directed energy and protein delivery (mean 26.0 kcal/kg/day and 1.3 g/kg/day, respectively), supported by frequent use of immunonutrition and enteral strategies where indicated.

Table 2. Nutritional parameters before and after optimization (N = 100)

Paired t-tests were used; values shown as mean ± SD.

3. Postoperative Morbidity Profile

Postoperative complications occurred in 42% of patients, with major morbidity (Clavien–Dindo grade ≥ III) in 25%. The 30-day mortality rate was 3%.

The most frequent complications were surgical site infection (SSI) in 15%, pneumonia in 10%, and acute kidney injury (AKI) in 8%. Procedure-specific complications included post-hepatectomy liver failure (PHLF) in 6%, postoperative pancreatic fistula (POPF) in 5%, and bile leak in 7%.

The median postoperative length of stay (LOS) was 11 days [IQR 8–15], and ICU admission was required in 20% of cases. Readmission within 30 days occurred in 10%.

Table 3. Postoperative morbidity profile (N = 100)

Values are presented as n (%) unless otherwise stated. LOS = length of stay

4. Comparison of Outcomes: Optimized vs Non-Optimized Patients

Of the 100 patients, 68 (68.0%) met predefined criteria for successful nutritional optimization. The remaining 32 (32.0%) were classified as non-optimized.

Major morbidity occurred in 14.7% of optimized patients compared with 46.9% in non-optimized patients (p = 0.001, χ² test), representing an absolute risk reduction (ARR) of 32.2% and a relative risk (RR) of 0.31 (95% CI, 0.16–0.59). Any morbidity was also significantly lower in the optimized group (30.9% vs 65.6%, p = 0.002).

Specific complications including SSI (7.4% vs 31.3%, p = 0.004), pneumonia (4.4% vs 21.9%, p = 0.012), and AKI (2.9% vs 18.8%, p = 0.018) occurred less frequently in the optimized group. Median postoperative LOS was 9 days [IQR 7–12] in optimized patients compared with 14 days [IQR 10–18] in non-optimized patients (p < 0.001, Mann–Whitney U test).

Table 4. Postoperative outcomes by nutritional optimization status

Values are n (%) unless otherwise stated. SSI = surgical site infection; AKI = acute kidney injury; POPF = postoperative pancreatic fistula; PHLF = post-hepatectomy liver failure; LOS = length of stay. p-values from χ²/Fisher’s exact tests for categorical variables and Mann–Whitney U tests for continuous variables.

5. Multivariate Analysis for Predictors of Major Morbidity

A multivariable logistic regression model was fitted with major morbidity (Clavien–Dindo ≥ III) as the dependent variable and the following covariates: optimization achieved (yes/no), age, BMI, cirrhosis, preoperative albumin, ASA (III/IV vs II), and surgery type (Major hepatectomy, Whipple, Biliary reconstruction; reference: Minor hepatectomy).

In the adjusted model, age was independently associated with higher odds of major morbidity (aOR 1.09 per year; 95% CI 1.03–1.16; p = 0.005). Achieving preoperative nutritional optimization was associated with lower odds of major morbidity (aOR 0.50; 95% CI 0.15–1.63; p = 0.250), indicating a protective trend that did not reach statistical significance after adjustment. Preoperative albumin showed a non-significant protective direction (aOR 0.75; 95% CI 0.31–1.81; p = 0.520). Cirrhosis, ASA, BMI, and surgery type were not statistically significant predictors in this model.

Model performance showed fair discrimination (AUC = 0.77), supporting reasonable ability to distinguish patients with and without major complications.

Table 5. Multivariable logistic regression for predictors of major morbidity (Clavien–Dindo ≥ III)

              OR = odds ratio; CI = confidence interval. Model discrimination: AUC 0.77.

6. Secondary Outcomes

Median postoperative length of stay (LOS) for the entire cohort was 11 days [IQR 8–15]. Patients achieving nutritional optimization had a significantly shorter LOS compared with those who did not (9 days [IQR 7–12] vs 14 days [IQR 10–18], p < 0.001).

ICU admission occurred in 20% of patients overall, but was markedly lower in the optimized group (11.8% vs 37.5%, p = 0.005). Readmission within 30 days occurred in 10% of patients, with no statistically significant difference between groups (p = 0.183).

The 30-day mortality rate was 3% for the entire cohort, with no significant difference by optimization status (1.5% vs 6.3%, p = 0.276).

Table 6. Secondary outcomes by nutritional optimization status

In this prospective interventional study, structured preoperative nutritional optimization in patients undergoing major hepatobiliary surgery was associated with a 32.2% absolute risk reduction in major postoperative morbidity (Clavien–Dindo ≥ III) and a median LOS reduction of 5 days. Nakajima et al. (2019) demonstrated that a combined program of preoperative exercise and nutritional therapy reduced postoperative complication rates in hepato-pancreato-biliary (HPB) surgery for malignancy, with an effect size comparable to our findings [7]. Similarly, Christopher et al. (2023) reviewed multimodal prehabilitation programs for HPB cancers and concluded that integrated nutrition interventions are most effective when initiated early, consistent with our median optimization duration of 12 days [8].

Our reduction in SSI from 31.3% to 7.4% mirrors the impact seen in the NutriCatt protocol, where personalized nutritional support within an ERAS framework reduced infection rates following liver resection [9]. Wu et al. (2025) also emphasized the role of targeted perioperative nutrition in hepatobiliary tumour surgery, reporting lower SSI and shorter LOS when nutritional goals were met [10]. In our cohort, pneumonia rates decreased from 21.9% to 4.4%, which aligns with the PRISMA-accordant meta-analysis by Lambert et al. (2021) showing that prehabilitation reduced pulmonary complications in major abdominal surgery, particularly when nutritional therapy was included [11].

Biochemically, serum albumin increased by 0.49 g/dL and CRP fell by 4.96 mg/L after optimization. Comparable improvements were reported by Zhang and Wang (2015) in end-stage liver disease patients undergoing transplantation, where preoperative nutrition reduced inflammatory markers and improved albumin [12]. Our functional gains — +2.01 kg handgrip strength and +1.01 cm²/m² skeletal muscle index — reinforce the observations of Thirunavukarasu and Aloia (2016), who highlighted the value of functional assessment in preoperative optimization for hepatic surgery [13]. DiNorcia and Colquhoun (2019) similarly stressed that improvements in protein-energy reserves translate into measurable perioperative performance gains [14].

Even patients classified as SGA A benefited from optimization in our study, echoing Kasvis et al. (2023), who found that dietary counselling improved health-related quality of life in HPB surgical candidates irrespective of baseline nutritional status [15]. This finding supports the concept that nutritional optimization should be universal rather than limited to malnourished individuals.

Our reduced ICU admission rate (11.8% vs 37.5%) and shortened LOS (9 vs 14 days) are in line with the ERAS Society recommendations for liver surgery, which endorse early nutritional intervention as a key component in reducing critical care utilization and length of stay [16]. Moreover, the direction of our results is consistent with the prehabilitation framework proposed by Hao et al. (2022), where older liver resection candidates benefitted from integrated preoperative conditioning [17].

In the adjusted regression model, age emerged as an independent predictor of major morbidity, with each additional year increasing the odds by 9% (aOR 1.09; 95% CI 1.03–1.16; p = 0.005). Nutritional optimization showed a protective association (aOR 0.50), though this did not reach statistical significance after adjustment. This pattern is consistent with Nakajima et al. (2019), who found that age remained a robust predictor of morbidity even when controlling for prehabilitation effects [7], and with Lambert et al. (2021), who reported that the benefits of nutritional optimization may be attenuated in older, high-comorbidity patients [11]. The lack of statistical significance for albumin and BMI in our model parallels findings from Thirunavukarasu and Aloia (2016), where functional and inflammatory markers were more predictive of outcome than static nutritional measures [13]. These results highlight that while optimization has clear unadjusted benefits, individual patient factors — especially age and baseline functional reserve — substantially influence surgical risk.

Strengths and limitations

Strengths of this study include its prospective design, standardized morbidity classification, and use of biochemical, anthropometric, and functional endpoints to define optimization. Unlike some earlier reports that focused solely on serum albumin, our protocol measured functional and inflammatory markers, providing a more holistic assessment. Limitations include the single-centre design, which may limit generalizability, and the relatively small sample size, which may have underpowered the detection of rare complications. Residual confounding is possible despite standardized perioperative protocols. As in previous literature [7, 11], the most definitive proof of causality would require a multicentre randomized trial.

Preoperative nutritional optimization in major hepatobiliary surgery was associated with a substantial reduction in major postoperative morbidity, shorter hospital stays, and fewer ICU admissions. Gains in biochemical, inflammatory, and functional parameters were observed even in patients without overt malnutrition, supporting a universal rather than selective optimization approach. These findings highlight nutritional prehabilitation as a feasible, low-risk, and clinically impactful strategy that warrants integration into standard perioperative care pathways and further evaluation in multicentre randomized trials.

1. Walcott-Sapp, S., & Billingsley, K. G. (2018). Preoperative optimization for major hepatic resection. Langenbeck's Archives of Surgery, 403(1), 23-35.
2. Liu, Y., & Xue, X. (2015). Systematic review of peri-operative nutritional support for patients undergoing hepatobiliary surgery. Hepatobiliary Surgery and Nutrition, 4(5), 304.
3. Evans, D. C., Martindale, R. G., Kiraly, L. N., & Jones, C. M. (2014). Nutrition optimization prior to surgery. Nutrition in Clinical Practice, 29(1), 10-21.
4. Wang, B., Shelat, V. G., Chow, J. J. L., Huey, T. C. W., Low, J. K., Woon, W. W. L., & Junnarkar, S. P. (2020). Prehabilitation program improves outcomes of patients undergoing elective liver resection. journal of surgical research, 251, 119-125.
5. Toh, E. Q., Wong, H. P. N., Wang, J. D. J., Liau, M. Y. Q., Tan, Y. F., & Shelat, V. G. (2024). Prehabilitation programs in liver resection: a narrative review. Chinese Clinical Oncology, 13(1), 9-9.
6. Wu, H., Guo, Z., Song, H., Wang, L., Gou, Y., Jin, S., ... & Sha, L. (2025). Perioperative nutritional management for patients with hepatobiliary tumours: a mini review. Holistic Integrative Oncology, 4(1), 29.
7. Nakajima, H., Yokoyama, Y., Inoue, T., Nagaya, M., Mizuno, Y., Kadono, I., ... & Nagino, M. (2019). Clinical benefit of preoperative exercise and nutritional therapy for patients undergoing hepato-pancreato-biliary surgeries for malignancy. Annals of surgical oncology, 26(1), 264-272.
8. Christopher, C. N., Kang, D. W., Wilson, R. L., Gonzalo-Encabo, P., Ficarra, S., Heislein, D., & Dieli-Conwright, C. M. (2023). Exercise and nutrition interventions for prehabilitation in hepato-pancreato-biliary cancers: a narrative review. Nutrients, 15(24), 5044.
9. Ardito, F., Lai, Q., Rinninella, E., Mimmo, A., Vellone, M., Panettieri, E., ... & Giuliante, F. (2020). The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: Results from the NutriCatt protocol. Updates in surgery, 72(3), 681-691.
10. Wu, H., Guo, Z., Song, H., Wang, L., Gou, Y., Jin, S., ... & Sha, L. (2025). Perioperative nutritional management for patients with hepatobiliary tumours: a mini.
11. Lambert, J. E., Hayes, L. D., Keegan, T. J., Subar, D. A., & Gaffney, C. J. (2021). The impact of prehabilitation on patient outcomes in hepatobiliary, colorectal, and upper gastrointestinal cancer surgery: a PRISMA-accordant meta-analysis. Annals of surgery, 274(1), 70-77.
12. Zhang, Q. K., & Wang, M. L. (2015). The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation. Hepatobiliary surgery and nutrition, 4(5), 336.
13. Thirunavukarasu, P., & Aloia, T. A. (2016). Preoperative Assessment and Optimization of the. Technical Aspects of Oncological Hepatic Surgery, An Issue of Surgical Clinics of North America, 96(2), 197.
14. DiNorcia, J., & Colquhoun, S. D. (2019). Perioperative Management and Nutritional Support in Patients With Liver and Biliary Tract Disease. In Shackelford's Surgery of the Alimentary Tract, 2 Volume Set (pp. 1410-1419). Elsevier.
15. Kasvis, P., Vigano, A., Bui, T., Carli, F., & Kilgour, R. D. (2023). Impact of dietary counseling on Health-Related quality of life in patients with cancer awaiting Hepato-Pancreato-biliary surgery. Nutrition and Cancer, 75(4), 1151-1164.
16. Melloul, E., Hübner, M., Scott, M., Snowden, C., Prentis, J., Dejong, C. H., ... & Demartines, N. (2016). Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) society recommendations. World journal of surgery, 40(10), 2425-2440.
17. Hao, S., Reis, H. L., Quinn, A. W., Snyder, R. A., & Parikh, A. A. (2022). Prehabilitation for older adults undergoing liver resection: getting patients and surgeons up to speed. Journal of the American Medical Directors Association, 23(4), 547-554.