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. 2026 Mar 25;33(7):513–525. doi: 10.1002/jhbp.70107

Incidence and Determinants of Steatotic Liver Disease after Pancreaticoduodenectomy: A Systematic Review and Meta‐Analysis

Ronnakorn Kongsakon 1, Wasit Wongtrakul 1, Khemajira Karaketklang 1, Nonthalee Pausawasdi 1, Phunchai Charatcharoenwitthaya 1,✉
PMCID: PMC13397199  PMID: 41879125

ABSTRACT

Background

Steatotic liver disease (SLD) is an unrecognized complication after pancreaticoduodenectomy (PD) and may affect nutrition and long‐term recovery. This meta‐analysis estimated the incidence of SLD after PD and identified its clinical and surgical risk factors.

Methods

MEDLINE and EMBASE were searched through March 2025 for studies reporting incident SLD after PD. Random‐effects models generated pooled incidence and risk estimates. Subgroup, meta‐regression, and sensitivity analyses assessed heterogeneity.

Results

Forty‐seven studies, including 6271 patients (mean age 65.8 ± 3.8 years; 42.9% female), predominantly from Asia, were included. The pooled incidence of SLD after PD was 26.2% (95% CI 22.6–30.3; I 2  = 90.5), with similar estimates across regions. Meta‐regression demonstrated that the timing of postoperative imaging influenced reported incidence. A higher risk of SLD was observed in women (OR 2.11), patients with obesity (OR 1.88) or hyperlipidemia (OR 1.57), and those undergoing PD for pancreatic ductal adenocarcinoma (OR 2.78). The classical Whipple procedure (RR 1.64, 95% CI 1.36–1.97) and adjuvant chemotherapy (RR 1.62, 95% CI: 1.28–2.07) were also associated with increased risk, whereas pancreatic enzyme replacement showed no significant protective effect.

Conclusions

Approximately a quarter of patients develop SLD after PD. These findings support longitudinal postoperative liver assessment and early nutrition‐focused management in surgical practice.

Keywords: chemotherapy, pancreatic enzyme replacement therapy, pancreaticoduodenectomy, steatotic liver disease, whipple procedure

1. Introduction

Pancreaticoduodenectomy (PD), or the Whipple procedure, remains the cornerstone operation for malignant and selected benign periampullary and pancreatic diseases. Continuous advances in surgical techniques and perioperative management have markedly reduced morbidity and mortality [1]. Consequently, the focus of contemporary research has shifted toward long‐term functional and metabolic sequelae after PD. Among these, steatotic liver disease (SLD) has emerged as an underrecognized yet clinically significant complication, with reported incidences as high as 38% [2, 3, 4, 5, 6]. Post‐PD SLD can progress to steatohepatitis, fibrosis, or liver failure, thereby impacting nutritional recovery, tolerance to adjuvant therapy, and overall survivorship.

Unlike metabolic dysfunction–associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD) [7, 8], SLD following PD appears to arise from distinct mechanisms unrelated to primary metabolic dysfunction. Proposed contributors include altered bile acid metabolism, impaired fat absorption, pancreatic exocrine and endocrine insufficiency, and postoperative changes in enterohepatic circulation and hormonal regulation [6, 9]. Surgical reconstruction type, residual pancreatic function, and the underlying disease pathology may further influence its development [10, 11]. Despite growing recognition of this entity, the true incidence and determinants of post‐PD SLD remain incompletely defined across studies. This systematic review and meta‐analysis aimed to clarify the pooled incidence, clinical characteristics, and risk factors associated with SLD following PD to inform postoperative surveillance and management strategies in HPB practice.

2. Methods

2.1. Search Strategy

A systematic literature search was independently conducted by two investigators (RK and WW) using EMBASE and MEDLINE, from database inception to March 2025, to identify reports of SLD after PD. The search strategy included terms related to hepatic steatosis (e.g., “Fatty Liver,” NAFLD/NAFL/NASH) with PD synonyms (e.g., Whipple, pancreatoduodenectomy/pancreaticoduodenectomy, duodenopancreatectomy), as detailed in Data S1. This study was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines (Data S2) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD420251012985).

2.2. Eligible Criteria

Studies were eligible if they enrolled adults (≥ 18 years) undergoing PD (classic Whipple or pylorus‐preserving) and reported the incidence of postoperative SLD or provided sufficient data to calculate it in a defined at‐risk cohort. We accepted author‐defined SLD diagnosed by histology, computed tomography (CT) (e.g., liver attenuation < 40 HU or liver/spleen attenuation ratio < 0.9 or liver < spleen by ≥ 10 HU), magnetic resonance imaging (MRI) (e.g., signal‐drop methods or liver fat signal fraction), or ultrasound with explicit criteria. Mixed pancreatectomy cohorts were included only when PD‐specific data were separately reported or extractable. Conference abstracts were eligible if they contained sufficient outcome data. Pediatric populations and reports without extractable PD‐specific SLD data were excluded. Titles/abstracts and full texts were screened independently by two reviewers (RK, WW), with disagreements resolved by a senior investigator (PC).

2.3. Data Extraction

For each eligible study, extracted data included study characteristics such as author, year of publication, study design, country, and data collection period. Patient characteristics included mean age, sex distribution, body mass index (BMI), and prevalence of metabolic comorbidities such as type 2 diabetes, hypertension, hyperlipidemia, and obesity. Information on diagnostic imaging modality and the timing of imaging after PD was recorded. Surgical and clinical variables included the indication for PD, type of surgery, incidence of SLD after PD, use of chemotherapy, pancreatic enzyme replacement therapy (PERT), and reported overall survival outcomes. Information on statistical adjustments and confounding factors included in multivariable regression analyses was recorded. Continuous variables reported as medians with ranges or interquartile ranges were standardized using the Box‐Cox transformation method to approximate mean and standard deviation values. Study quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool.

2.4. Statistical Analysis

The incidence of SLD following PD was either directly extracted from studies or calculated using raw data by dividing the number of incident cases by the total number of individuals at risk. Pooled incidence estimates were derived using the DerSimonian‐Laird random‐effects model with Logit transformation, and a 95% confidence interval (CI) was calculated using the Wilson score method. Heterogeneity across studies was assessed using Cochran's Q test and I 2 statistics, with substantial heterogeneity defined as p < 0.10 for the Q‐statistic and I 2  > 50% [12]. A random‐effects model was applied to all analyses regardless of heterogeneity levels [13].

Clinical factors associated with SLD after PD were analyzed using odds ratios (ORs) for categorical variables and mean differences (MDs) for continuous variables, both estimated via the DerSimonian‐Laird method [14]. Subgroup analyses were conducted to explore potential sources of heterogeneity, considering study region, publication year, study design, publication type, diagnostic imaging modality, timing of imaging after PD, and JBI quality scores. Study quality was categorized as low (≥ 8), moderate (7), or high risk of bias (≤ 6) based on JBI scores. Mixed‐effects meta‐regression analyses assessed variations across studies, incorporating factors such as mean age, sex distribution, mean BMI, and the prevalence of type 2 diabetes, hypertension, hyperlipidemia, obesity, chronic pancreatitis, type of surgery, study region, publication year, study design, publication type, imaging modality, timing of imaging after PD, and JBI scores. A leave‐one‐out sensitivity analysis was performed to evaluate the influence of individual studies on the overall results by sequentially excluding each study. Additionally, relative risks (RRs) were estimated for SLD development in patients undergoing different surgical approaches (classical Whipple vs. pylorus‐preserving PD), receiving chemotherapy (chemotherapy vs. no chemotherapy), and receiving PERT (PERT vs. no PERT). Publication bias was assessed using funnel plots and Egger's test when at least 10 studies were available [15]. All statistical analyses were conducted using STATA 14 (StataCorp LP, College Station, Texas, USA).

3. Results

3.1. Study Selection

A total of 522 studies were initially identified, with 231 from EMBASE and 291 from MEDLINE. After excluding 51 duplicate articles, 471 studies underwent the first round of screening. Of these, 96 articles proceeded to a second round of full‐text review, and ultimately, 47 studies met the inclusion criteria for final analysis [2, 3, 4, 5, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58]. These studies comprised 42 retrospective cohort studies, four prospective cohort studies, and one randomized controlled trial, all reporting incident cases of SLD following PD. Among the selected studies, 34 were full‐text articles, and 13 were conference abstracts. The study selection process is illustrated in Figure 1.

FIGURE 1.

FIGURE 1

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Flowchart of literature review and study selection.

3.2. Study Characteristics

The characteristics of the included studies are summarized in Data S3 and S4. A total of 47 studies conducted between 2007 and 2025, involving 6271 patients who underwent PD, were included in the analysis. Most of the studies were conducted in Asia, with 32 studies from Japan, three from Korea, and one each from China and Thailand. Seven studies were conducted in the United States, with one study each from Belgium, the Netherlands, and France. The most commonly used diagnostic modality for SLD was CT, with hepatic steatosis defined by a liver attenuation of < 40 Hounsfield units or a liver‐to‐spleen ratio < 0.9. The timing of postoperative imaging varied widely, from as early as 3 months to beyond 3 years after PD. Imaging was conducted within 6 months in 13 studies, within 12 months in 17 studies, within 2 years in 6 studies, and beyond 2 years in 6 studies, while 5 studies did not report the timing of imaging.

The mean age of participants was 65.8 ± 3.8 years (range: 53.9–71.9 years), and the mean BMI was 22.7 ± 2.1 kg/m2 (range: 20.4–28.0 kg/m2). Overall, 42.9% of patients were female. The prevalence of metabolic comorbidities was 24.5% for obesity, defined as a BMI ≥ 30 kg/m2 (range: 22.0%–26.0%), 27.3% for type 2 diabetes mellitus (range: 10.0%–78.9%), 44.8% for hypertension (range: 26.2%–57.0%), and 17.8% for hyperlipidemia (range: 7.0%–40.0%). Pre‐existing chronic pancreatitis was present in 15% of patients. The overall methodological quality of the included studies, as assessed by the JBI Checklist, was moderate to good (Data S4).

3.3. Incidence of Steatotic Liver Disease After Pancreaticoduodenectomy

The pooled incidence of SLD following PD, as determined by meta‐analysis, was 26.2% (95% CI: 22.6–30.3; I 2  = 90.5%) (Figure 2). The funnel plot (Data S5) did not reveal evidence of significant publication bias, as confirmed by Egger's test (p = 0.061).

FIGURE 2.

FIGURE 2

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Forest plot displaying the pooled incidence of steatotic liver disease after pancreaticoduodenectomy.

Subgroup analyses to explore sources of variability between studies are presented in Table 1. The pooled incidence of SLD after PD was 25.7% (95% CI: 21.6–29.9; I 2  = 90.9%) for studies conducted in Asian countries and 28.3% (95% CI: 19.7–37.6; I 2  = 89.9%) for studies conducted in Western countries. Studies published before 2017 showed a pooled incidence of 25.9% (95% CI: 21.2–30.9; I 2  = 85.6%), which was similar to that of studies published after 2017 (26.4%, 95% CI: 21.1–32.1; I 2  = 92.9%). Full‐text articles reported an incidence of 26.1% (95% CI: 22.3–30.0; I 2  = 87.7%), comparable to that of conference abstracts (26.2%, 95% CI: 17.4–36.0; I 2  = 94.5%). Retrospective and prospective studies showed similar pooled incidences of 26.1% (95% CI: 22.3–30.0; I 2  = 90.5%) and 26.9% (95% CI: 13.4–42.9; I 2  = 92.4%), respectively. When stratified by diagnostic modality, studies using CT alone reported a pooled incidence of 26.5% (95% CI: 22.5–30.7; I 2  = 90.9%), while higher estimates were observed in studies employing magnetic resonance imaging and/or CT (36.8%, 95% CI: 28.8–45.1; I 2  = 84.4%). Lower incidence was noted in studies using CT and/or histology (20.6%, 95% CI: 11.9–30.7). Analysis by timing of postoperative imaging revealed a progressive increase in SLD incidence with longer follow‐up, from 20.9% within 6 months to 29.7% within 12 months, 29.1% within 2 years, and 34.6% beyond 2 years. Stratification by study quality using the JBI tool showed pooled incidences of 22.2% for scores ≤ 6, 30.2% for scores of 7, and 22.9% for scores ≥ 8 (Table 1).

TABLE 1.

Pooled incidence of steatotic liver disease following pancreaticoduodenectomy stratified by publication year, study region, publication type, study design, diagnostic imaging modality, timing of imaging, and JBI score.

No. of studies No. population Incidence % (95% CI) I 2 (%)
Overall 47 6271 26.2 (22.6–30.0) 90.5
Publication year
≤ 2017 22 2329 25.9 (21.2–30.9) 85.6
> 2017 25 3942 26.4 (21.1–32.1) 92.9
Region
Western 10 1144 28.3 (19.7–37.6) 89.9
Eastern 37 5127 25.7 (21.6–29.9) 90.9
Publication type
Full‐text article 34 4576 26.1 (22.3–30.0) 87.7
Conference abstract 13 1695 26.2 (17.4–36.0) 94.5
Study design
Retrospective 42 5797 26.1 (22.3–30.0) 90.5
Prospective/clinical trial 5 474 26.9 (13.4–42.9) 92.4
Diagnostic modality
CT 39 5316 26.5 (22.5–30.7) 90.9
MRI and/or CT 4 707 36.8 (28.8–45.1) 84.4
CT and/or Biopsy 2 136 20.6 (11.9–30.70) —
Unknown 2 112 20.2 (13.1–28.3) —
Timing of imaging after PD
Within 6 months 13 1647 20.9 (16.2–26.0) 82.3
Within 12 months 17 2058 29.7 (23.0–36.9) 91.4
Within 2 years 6 1186 29.1 (23.5–35.1) 64.3
Beyond 2 years 6 537 34.6 (20.6–50.2) 92.3
Unknown 5 843 15.1 (8.5–23.1) 85.8
JBI score
≤ 6 9 840 22.2 (13.3–32.7) 91.2
7 23 2232 30.2 (24.2–36.6) 90.0
≥ 8 15 3199 22.9 (18.1–28.1) 90.2
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Abbreviations: CI, confidence interval; JBI, Joanna Briggs Institute.

A meta‐regression analysis was performed to assess study‐level factors associated with the reported incidence of SLD. At the study level, no significant associations were observed for mean age, sex distribution, mean BMI, or the prevalence of metabolic comorbidities, including type 2 diabetes, obesity, hypertension, or hyperlipidemia, nor for publication characteristics, diagnostic modality, or study quality (Table 2). In contrast, the timing of postoperative imaging was associated with SLD incidence, with higher estimates in studies assessing imaging within 12 months after PD (OR 1.09, 95% CI 1.01–1.20) and beyond 2 years (OR 1.16, 95% CI 1.02–1.32) compared with studies evaluating within 6 months. Sensitivity analyses using a leave‐one‐out approach demonstrated stable pooled incidence estimates, ranging from 25.4% to 26.7% (Data S6), suggesting that no single study disproportionately influenced the overall findings.

TABLE 2.

Univariate meta‐regression analyses evaluating the impact of study characteristics on the incidence of steatotic liver disease following pancreaticoduodenectomy.

Number of studies Univariate analysis
OR (95% CI) p R2 (%)
Mean age, years 36 0.99 (0.98–1.01) 0.544 0.00
< 65 10 Reference
≥ 65 26 0.96 (0.87–1.07) 0.449
Male, % 35 0.99 (0.98–1.001) 0.053 23.01
Mean BMI, kg/m2 27 0.99 (0.97–1.03) 0.973 0.00
≤ 25 23 Reference
> 25 4 1.07 (0.91–1.26) 0.423
Type 2 Diabetes, % 22 1.003 (0.99–1.01) 0.259 8.65
Hypertension, % 5 1.003 (0.97–1.04) 0.819 0.00
Hyperlipidemia, % 6 0.99 (0.98–1.02) 0.980 0.00
Obesity, % 5 0.95 (0.84–1.07) 0.269 17.45
Chronic pancreatitis, % 6 1.00 (0.99–1.01) 0.792 0.00
Classical Whipple, % 6 0.99 (0.98–1.01) 0.540 0.00
PPPD, % 7 0.99 (0.98–1.01) 0.487 0.00
Publication year 0.00
≤ 2017 22 Reference
> 2017 25 1.00 (0.93–1.08) 0.967
Region 0.00
Western 10 Reference
Eastern 37 0.99 (0.90–1.09) 0.844
Publication type 0.00
Full‐text article 34 Reference
Conference abstract 13 1.02 (0.93–1.11) 0.748
Study design 1.60
Retrospective 42 Reference
Prospective/clinical trial 5 1.01 (0.88–1.15) 0.916
Diagnostic modality 5.88
CT 39 Reference
MRI and/or CT 4 0.92 (0.81–1.05) 0.218 5.88
CT and/or Biopsy 2 1.11 (0.89–1.37) 0.343
Unknown 2 0.94 (0.74–1.18) 0.569
Timing of imaging after PD 30.89
Within 6 months 13 Reference
Within 12 months 17 1.09 (1.01–1.20) 0.049
Within 2 years 6 1.09 (0.97–1.22) 0.162
Beyond 2 years 6 1.16 (1.02–1.32) 0.021
Unknown 5 0.95 (0.84–1.08) 0.442
JBI score 13.28
≤ 6 9 Reference
7 23 1.07 (0.96–1.19) 0.227
≥ 8 14 0.98 (0.88–1.10) 0.775
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Abbreviations: CI, confidence interval; CT, computed tomography; JBI, Joanna Briggs Institute; MRI, magnetic resonance imaging; OR, odds ratio; PPPD, pylorus preserving pancreaticoduodenectomy.

3.4. Characteristics of Patients Who Developed Steatotic Liver Disease Following Pancreaticoduodenectomy

Table 3 summarizes patient‐level characteristics associated with the development of SLD after PD. At the individual level, age and BMI did not differ significantly between patients who developed SLD and those who did not. However, several baseline factors were associated with increased risk of SLD. Patients who developed SLD were more frequently female (OR 2.11, 95% CI 1.71–2.60; p < 0.001) and had a higher prevalence of baseline obesity (OR 1.88, 95% CI 1.17–3.01; p = 0.009). Hyperlipidemia was also more common among patients with SLD (OR 1.57, 95% CI 1.08–2.29; p = 0.018). In contrast, the prevalence of pre‐existing type 2 diabetes mellitus and hypertension did not differ significantly between groups. In addition, pancreatic ductal adenocarcinoma (PDAC) as the indication for PD was strongly associated with subsequent development of SLD (OR 2.78, 95% CI 2.07–3.74; p < 0.001).

TABLE 3.

Clinical characteristics of patients who developed steatotic liver disease following pancreaticoduodenectomy.

Studies, n SLD No SLD Effect size (95% CI) I2, % p
Age (years), mean (SD) 19 64.9 (3.8) 66.8 (2.7) MD −0.14 (−0.31 to 0.02) 61.3 0.094
Female, n (%) 24 406 (55.7) 974 (37.5) OR 2.11 (1.71 to 2.60) 26.1 < 0.001
BMI (kg/m2), mean (SD) 20 23.1 (2.5) 22.7 (2.2) MD 0.14 (−0.02 to 0.31) 61.1 0.085
Obesity, n (%) 5 75 (33.5) 179 (22.1) OR 1.88 (1.17 to 3.01) 46.6 0.009
Type 2 Diabetes, n (%) 17 164 (27.4) 527 (24.5) OR 1.18 (0.85 to 1.66) 46.9 0.327
Hypertension, n (%) 5 110 (49.1) 403 (49.4) OR 1.01 (0.73 to 1.42) 9.8 0.933
Hyperlipidemia, n (%) 6 63 (26.6) 193 (23.3) OR 1.57 (1.08 to 2.29) 0.0 0.018
PDAC, n (%) 18 377 (70.1) 871 (45.0) OR 2.78 (2.07 to 3.74) 38.3 < 0.001
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Abbreviations: BMI, body mass index; CI, confidence interval; MD, mean difference; OR, odds ratio; PDAC, pancreatic duct adenocarcinoma; SD, standard deviation.

3.5. Effects of Intervention on Developing Steatotic Liver Disease After Pancreaticoduodenectomy

Sensitivity analyses were performed to evaluate the impact of surgical techniques and therapeutic interventions on SLD development. Data from seven studies involving 1360 patients indicated that the classical Whipple procedure carried a significantly higher risk of SLD compared to pylorus‐preserving PD (RR 1.64, 95% CI: 1.36–1.97), with low heterogeneity (I 2  = 0%) (Figure 3A) [2, 3, 4, 28, 29, 31, 49]. Additionally, nine studies comprising 1421 patients with pancreatic cancer evaluated the relationship between chemotherapy and SLD (Data S7) [19, 32, 36, 37, 42, 44, 47, 54, 55]. Most studies investigated adjuvant chemotherapy with fluorouracil, gemcitabine, or S‐1, demonstrating a significant increase in SLD risk among patients receiving chemotherapy (RR 1.71, 95% CI: 1.25–2.23), with moderate heterogeneity (I 2  = 49.1%) (Figure 3B). In subgroup analyses, adjuvant chemotherapy evaluated in seven studies was significantly associated with an increased risk of SLD (RR 1.62, 95% CI: 1.28–2.07) with no observed heterogeneity (I 2  = 0.0%) [19, 32, 36, 42, 44, 54, 55]. In contrast, neoadjuvant or combined neoadjuvant/adjuvant chemotherapy evaluated in two studies was not significantly associated with SLD (RR 1.90, 95% CI: 0.45–8.11), and substantial heterogeneity was observed (I 2  = 90.9%) [37, 47]. Furthermore, seven studies including 902 patients evaluated the effects of PERT, which was administered at varying doses for durations ranging from 3 months to 2 years postoperatively (Data S8) [4, 19, 23, 33, 35, 44, 55]. While PERT use showed a trend toward reducing SLD risk, the association did not reach statistical significance (RR 0.97, 95% CI: 0.62–1.52, I 2  = 48.6%) (Figure 3C). Funnel plot analysis of surgical techniques and therapeutic interventions on the development of SLD showed no evidence of publication bias (Data S9).

FIGURE 3.

FIGURE 3

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Forest plot displaying the relative risk of (A) classic Whipple procedure, (B) chemotherapy, and (C) pancreatic enzyme replacement therapy on the development of steatotic liver disease after pancreaticoduodenectomy.

3.6. Effects of Steatotic Liver Disease After Pancreaticoduodenectomy on Overall Survival

Available evidence indicates that SLD developing after PD does not significantly affect survival outcomes. Sato et al. reported no significant difference in overall survival between patients with and without SLD after PD (log‐rank p = 0.716) [4]. Okabe et al. similarly observed comparable 5‐year overall survival, despite higher rates of malnutrition and reduced completion of adjuvant chemotherapy among patients with SLD [47]. In the largest cohort, Huang et al. found no difference in overall survival between post‐PD SLD and non‐SLD patients (long‐rank p = 0.969), including PDAC and periampullary carcinoma subgroups [26]. Consistent with these findings, Okamura et al. demonstrated similar 3‐year overall survival between patients with postoperative SLD and those without (55.8% vs. 61.7%; p = 0.700) [11]. Notably, in a subset analysis of patients who developed SLD within 3–12 months after PD, follow‐up unenhanced CT at 12–18 months showed resolution of SLD in 45% of cases. Patients with improvement of SLD had a higher cumulative overall survival at 60 months compared with those without improvement (75.0% vs. 21.4%), although this difference did not reach statistical significance. In addition, Flick et al. reported no significant difference in early postoperative mortality, with comparable 90‐day survival between patients with PDAC receiving neoadjuvant chemotherapy who developed SLD and those who did not [20].

4. Discussion

This meta‐analysis provides a comprehensive evaluation of the incidence of SLD following PD and identifies factors associated with its development. The pooled incidence of SLD after PD was 26.2%, with comparable rates across Asia and Western countries, study designs, and no meaningful temporal variations. Subgroup and meta‐regression analyses demonstrated that study‐level factors, including mean age, sex distribution, mean BMI, the prevalence of metabolic comorbidities, diagnostic modality, and study quality, were not associated with SLD incidence. In contrast, the timing of postoperative imaging influenced reported incidence, with higher rates observed in studies performing imaging within 12 months after surgery and beyond 2 years compared with those assessing within 6 months, indicating increased detection with longer follow‐up. At the individual level, SLD after PD was more frequent among women and patients with obesity or hyperlipidemia, and was more common when PD was performed for PDAC. In addition, adjuvant chemotherapy, particularly fluorouracil‐, gemcitabine‐, or S‐1‐based regimens, was strongly associated with an increased risk of SLD. Among surgical techniques, the classical Whipple procedure conferred a higher risk of SLD, while PERT showed a non‐significant protective trend.

PD is a complex surgical procedure primarily performed for pancreatic and periampullary malignancies. Following PD, hepatic steatosis has been increasingly recognized as a complication. The mechanisms underlying SLD following PD differ from those of MASLD [9, 59]. In the case of MASLD, insulin resistance and obesity are primary drivers of hepatic steatosis, while in PD patients, disruption of enterohepatic circulation and changes in digestive hormone secretion are believed to play a more central role. Particularly, insufficient pancreatic enzyme production may impair nutrient absorption, exacerbating insulin resistance and promoting hepatic fat accumulation [54, 60]. As surgical techniques advance and perioperative mortality rates decrease, there is a growing emphasis on addressing long‐term postoperative complications, including SLD. This shift highlights the critical need for comprehensive postoperative care and continuous monitoring to manage these emerging challenges effectively.

This systematic review and meta‐analysis established a pooled SLD incidence of 26.2% following PD, with relatively consistent estimates across regions, study designs, and time periods, in keeping with previously reported rates of 8%–37% [59]. Sensitivity analyses showed minimal variation in the pooled estimate after sequential exclusion of individual studies, supporting the robustness of this finding and underscoring the clinical relevance of postoperative SLD. At the study level, most examined characteristics, including mean age, sex distribution, mean BMI, and the prevalence of metabolic comorbidities such as type 2 diabetes, obesity, hypertension, and hyperlipidemia, diagnostic modality, and study quality, were not associated with variability in reported SLD incidence across studies. In contrast, the timing of postoperative imaging influenced detection, with higher incidence reported in studies performing imaging within 12 months or later compared with those evaluating within 6 months after surgery, suggesting that SLD may evolve over time and be underestimated with shorter follow‐up.

At the individual patient level, several characteristics were associated with an increased risk of developing SLD after PD, highlighting the interaction between baseline metabolic susceptibility and PD‐specific physiological stress. Female sex was associated with a higher SLD risk. Although the precise mechanisms remain incompletely understood, evidence from MASLD provides biological plausibility. In the general population, postmenopausal women exhibit a higher prevalence and more rapid progression of hepatic steatosis, largely attributable to estrogen deficiency [61]. Estrogen plays a protective role in hepatic lipid homeostasis through regulation of insulin sensitivity, fatty acid oxidation, and adipose tissue distribution [62]. Declining estrogen levels may therefore predispose women to hepatic fat accumulation and a vulnerability that may be further amplified after PD by surgical stress, altered bile acid circulation, and postoperative nutritional impairment [9].

Preoperative obesity and hyperlipidemia were also associated with an increased risk of SLD after PD, consistent with their established roles as metabolic drivers in hepatic steatosis [63]. Excess adiposity and dyslipidemia increase hepatic delivery of free fatty acids to the liver and promote triglyceride accumulation, creating a metabolically vulnerable state before surgery [64]. Following PD, this vulnerability may be amplified by pancreatic exocrine insufficiency, impaired fat digestion and absorption, postoperative catabolism with preferential loss of lean body mass, and ongoing inflammatory stress [9]. Together, these factors favor hepatic lipid storage over oxidation, increasing the likelihood of steatosis. These findings highlight the importance of perioperative metabolic assessment and targeted nutritional and lipid management strategies in patients at higher risk undergoing PD.

The higher incidence of SLD among patients undergoing PD for PDAC likely reflects an interplay between disease‐related metabolic disturbances and treatment‐related factors. PDAC is commonly accompanied by cancer‐associated cachexia, systemic inflammation, and pancreatic exocrine insufficiency [65, 66, 67], which impair nutrient digestion and absorption and may predispose patients to hepatic lipid accumulation. Within this context, our findings suggest that adjuvant chemotherapy is associated with an increased risk of postoperative SLD, potentially exacerbating metabolic vulnerability in the post‐PD setting rather than acting as an isolated causal factor [19, 32, 36, 42, 44, 54, 55]. Experimental and clinical data indicate that fluorouracil‐, gemcitabine‐, and S‐1–based regimens can induce mitochondrial dysfunction, oxidative stress, and alterations in hepatic lipid metabolism [68, 69, 70], which may act synergistically with surgical stress and pancreatic insufficiency to promote steatosis. Nevertheless, residual confounding related to disease severity, nutritional status, and treatment selection cannot be fully excluded given the observational nature of the available data. In contrast, neoadjuvant chemotherapy was not significantly associated with SLD in the limited number of available studies [37, 47]. Although this analysis was underpowered and characterized by substantial heterogeneity, the absence of a clear association raises the possibility that the timing of chemotherapy exposure relative to surgical resection may influence postoperative hepatic outcomes. Neoadjuvant therapy is administered in the setting of an intact pancreas and gastrointestinal tract, which may better preserve digestive and metabolic homeostasis and attenuate downstream effects on hepatic lipid handling. As neoadjuvant treatment strategies are increasingly incorporated into contemporary PDAC management, particularly for borderline resectable disease, further studies are needed to clarify whether chemotherapy timing differentially affects the risk of postoperative SLD and to disentangle treatment effects from underlying disease‐related factors.

Surgical reconstruction technique also appeared to influence SLD risk. Patients undergoing the classical Whipple procedure had a higher incidence of SLD compared with those treated with pylorus‐preserving PD [2, 3, 4, 28, 29, 31, 49]. Resection of the distal stomach and duodenum in the classical Whipple may lead to more profound disruptions in gastrointestinal physiology, including altered secretion of gut hormones, disruption of bile acid circulation, and impaired synchronization of pancreatic exocrine output [71, 72]. These changes can compromise lipid digestion and absorption and shift hepatic lipid storage over oxidation, thereby increasing susceptibility to steatosis. Preservation of the pylorus may better maintain physiological gastric emptying and enterohepatic signaling, potentially mitigating these effects and reducing SLD risk [31].

PERT is commonly used to alleviate malabsorption and improve nutritional status after pancreatic surgery. In this meta‐analysis, PERT was associated with a non‐significant trend toward lower SLD incidence [4, 19, 23, 33, 35, 44, 55]. The lack of statistical significance may reflect heterogeneity in dosing strategies, treatment duration, and adherence across studies. Nonetheless, this trend suggests that optimization of PERT may play a supportive role in mitigating postoperative hepatic steatosis and warrants further evaluation in prospective studies.

Overall, available evidence indicates that the development of SLD after PD does not appear to adversely affect overall survival [4, 11, 20, 26, 47]. However, the influence of the timing of onset and duration of SLD on survival remains uncertain, as most studies evaluated SLD at variable postoperative time points without distinguishing early versus late onset or transient versus persistent disease. Limited observational data suggest that resolution of SLD may be associated with more favorable long‐term outcomes, whereas persistent or progressive SLD could be clinically relevant, although these associations have not been demonstrated conclusively [11]. Prospective studies incorporating standardized diagnostic criteria and longitudinal, time‐dependent survival analyses are needed to clarify whether the persistence or progression of SLD, rather than its presence alone, influences overall survival.

These findings have several clinical implications. First, SLD should be recognized as a common postoperative condition warranting structured hepatic surveillance after PD. Second, patients with obesity, dyslipidemia, or PDAC, particularly those receiving adjuvant chemotherapy, may benefit from closer monitoring for early hepatic steatosis. Third, optimization of PERT and individualized nutritional support may help mitigate metabolic disturbances related to fat malabsorption. Such strategies, supported by multidisciplinary follow‐up, may improve long‐term survivorship and quality of life after PD. However, this study has limitations. Despite subgroup and sensitivity analyses, substantial heterogeneity persisted, likely due to variations in diagnostic criteria, surgical techniques, chemotherapy regimens, and enzyme replacement protocols. Most included studies were retrospective, and definitions of SLD were not standardized, limiting causal inference. Future prospective studies with uniform imaging protocols, standardized enzyme replacement strategies, and detailed metabolic assessments are required to better define the natural history, prognostic implications, and preventive approaches for postoperative SLD.

In conclusion, this meta‐analysis demonstrates that SLD develops in approximately one quarter of patients after PD and is influenced by both patient‐related metabolic vulnerability and PD‐specific factors. The findings underscore the importance of postoperative liver monitoring, nutritional optimization, and further research aimed at reducing hepatic complications in hepatopancreatobiliary surgery.

Author Contributions

Conceptualization and original draft: Ronnakorn Kongsakon and Phunchai Charatcharoenwitthaya. Methodology, and formal analysis: Khemajira Karaketklang, Nonthalee Pausawasdi, and Phunchai Charatcharoenwitthaya. Data curation, Investigation, and data resources: Ronnakorn Kongsakon and Wasit Wongtrakul. Project administration: Phunchai Charatcharoenwitthaya. Supervision: Phunchai Charatcharoenwitthaya. Critical review and final approval of manuscript: All authors.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Data S1: PRISMA checklist.

Data S2: Search strategy.

Data S3: Characteristics of the included studies reporting the incidence of steatotic liver disease after pancreaticoduodenectomy.

Data S5: Funnel plot assessing publication bias in studies investigating the incidence of steatotic liver disease following pancreaticoduodenectomy.

Data S6: Pooled incidence of steatotic liver disease following pancreaticoduodenectomy by leave‐one‐out meta‐analysis.

Data S7: Study evaluating chemotherapy on the development of steatotic liver disease following pancreaticoduodenectomy.

Data S8: Study evaluating pancreatic enzyme replacement therapy on the development of steatotic liver disease following pancreaticoduodenectomy.

Data S9: Funnel plot assessing publication bias in studies investigating the effects of (A) classic Whipple procedure, (B) chemotherapy, and (C) pancreatic enzyme replacement therapy on the development of steatotic liver disease following pancreaticoduodenectomy.

JHBP-33-513-s001.docx (598KB, docx)

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Data S1: PRISMA checklist.

Data S2: Search strategy.

Data S3: Characteristics of the included studies reporting the incidence of steatotic liver disease after pancreaticoduodenectomy.

Data S5: Funnel plot assessing publication bias in studies investigating the incidence of steatotic liver disease following pancreaticoduodenectomy.

Data S6: Pooled incidence of steatotic liver disease following pancreaticoduodenectomy by leave‐one‐out meta‐analysis.

Data S7: Study evaluating chemotherapy on the development of steatotic liver disease following pancreaticoduodenectomy.

Data S8: Study evaluating pancreatic enzyme replacement therapy on the development of steatotic liver disease following pancreaticoduodenectomy.

Data S9: Funnel plot assessing publication bias in studies investigating the effects of (A) classic Whipple procedure, (B) chemotherapy, and (C) pancreatic enzyme replacement therapy on the development of steatotic liver disease following pancreaticoduodenectomy.

JHBP-33-513-s001.docx (598KB, docx)

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article.

Articles from Journal of Hepato-Biliary-Pancreatic Sciences are provided here courtesy of Wiley

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