The Prevalence and Association Between Non-Alcoholic Fatty Pancreas Disease and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Introduction: Non-alcoholic Fatty Pancreas Disease (NAFPD), which refers to fat accumulation in the pancreas with subsequent development of pancreatic and metabolic complications, has been linked to metabolic syndrome, abnormal glucose metabolism and liver fat deposition in non-alcoholic fatty liver disease (NAFLD). The prevalence and association of NAPFD and NAFLD still remains unclear. We aimed to conduct a systematic review and meta-analysis assessing the prevalence and association of NAFPD in patients with NAFLD. Methods: A comprehensive search of multiple databases including MEDLINE (OVID), Cochrane Library, Embase, Scopus, SciELO and Web of Science was conducted from inception to April 2023 for all published studies that reported the prevalence of NAFPD among patients with NAFLD in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Two independent reviewers extracted data. Disagreements were resolved by a third author. Pooled prevalences and pooled odds ratios (OR) were calculated after Freeman-Tukey Double Arcsine Transformation. Heterogeneity was assessed using the Higgins I2 index. Results: Among 1520 articles identified, 163 studies were identified for full text review and 18 studies were eligible for inclusion, with perfect agreement between investigators (kappa=1.0). Eight of them were cross sectional. A total of 8933 patients with NAFLD were included in the studies (Table 1). The majority of studies were conducted in an outpatient setting and utilized Abdominal Ultrasound (US) to diagnose NAFLD and NAFPD. The overall pooled prevalence of NAFPD was noted to be 42.59% (Figure 1) with high heterogeneity (I2=98.74%). Pooled OR with 95% confidence interval (CI) for NAFPD in patients with NAFLD was 3.24 (2.07-3.06), I2=74.93% (Figure 1). Conclusion: Our meta-analysis demonstrates that NAFPD can be found in almost half of patients with NAFLD. Also, NAFLD was significantly associated with an increased risk of having NAFPD. Further studies are needed to evaluate the nature of this association and to what extent NAFPD is a consequence of NAFLD or a contributing factor. This will help elucidate mechanisms involved, complications, clinical consequences, and novel therapies for these conditions. Table 1. - Characteristics of included studies Author Study year Study design Country Setting Study Population Female (%) Mean age (SD) Mode of Diagnosis of NAFLD NAFLD (N) Controls (N) Mode of Diagnosis of NAFPD NAFPD in Patients with NAFLD (N) NAFPD in Controls (N) NAFPD in patients with NAFLD (%) NAFPD in Controls (%) (if reported) OR P-value Altinmakas 2021 Retrospective Turkey Outpatient clinic Adult healthy renal transplantation donors 49.40% 46.3 ± 13.5 Computed Tomography 52 270 Computed Tomography 26 59 50.00% 21.85% 2.29 (1.92-3.96) NR Berger 2021 Retrospective Chile Outpatient clinic Healthy adults 107 (53%) 55 ± 12 Computed Tomography 55 148 Computed Tomography 19 42 34.54% 28.37% 1.22 (0.65-2.27) 0.394 Bi 2022 Retrospective China Outpatient clinic Adult volunteers for comprehensive health screening 3636 (28.96%) NR Endoscopic ultrasound 4732 NA Endoscopic ultrasound 770 NR 16.27% NR NR NR Chan 2022 Retrospective China Outpatient clinic Adults invited by mail and telephone calls to undergo evaluation of NAFLD 388 (61.5%) 48 ± 11 years Magnetic Resonance Spectroscopy (MRS) 165 NA Magnetic Resonance Spectroscopy (MRS) 67 NA 40.60% NR NR NR Khoury 2021 Retrospective Israel Tertiaty Center Patients who underwent EUS for non-acute hepatobiliary indication 267 (46.92%) NR Endoscopic ultrasound 298 271 Endoscopic ultrasound 66 12 22.14% 4.42%% 5.94 (3.16–11.16) < 0.0001 Lesmana 2015 Cross-sectional study Indonesia Outpatient clinic Adults undergoing health screening 334 (31.68%) 43.1 ± 12.19 Abdominal Ultrasound 437 519 Abdominal Ultrasound 232 83 53.08% 15.90% 5.195 (3.838-7.032) < 0.001 Milovanovic 2019 Cross-sectional study Serbia Outpatient clinic Adults with known NAFLD 46 (32.16%) NR Abdominal Ultrasound 143 NA Abdominal Ultrasound 84 NA 58.74% NR NR NR Okada 2021 Cross-sectional study Japan Outpatient clinic Adults undergoing health screening 45.70% 59.5 ± 13.2 Abdominal Ultrasound 314 NA Abdominal Ultrasound 246 NA 78.34% NR NR NR Osman 2022 Cross-sectional study Egypt Outpatient clinic Women with PCOS 100% NR Abdominal Ultrasound 77 NA Abdominal Ultrasound 32 NA 41.55% NR NR NR Sahin 2022 Retrospective Turkey Outpatient clinic Adults with known NAFLD 57.92% 53.6 ± 9.7 Abdominal Ultrasound 183 NA Abdominal Ultrasound 98 NA 53.55% NR NR NR Sbeit 2021 Cross-sectional study Israel Outpatient clinic Patients who underwent EUS for non-acute hepatobiliary indication 46.92% 62.9 ± 14.1 Abdominal Ultrasound 298 271 Abdominal Ultrasound 66 12 22.15% 4.43% 5.94 (3.16-11.16) < 0.0001 Sbeit, W; Mahamid, M 2021 Case-Control Study Israel Outpatient clinic Patients who underwent EUS for non-acute hepatobiliary indication 46.23% 61.2 ± 14.7 Endoscopic ultrasound 278 267 Endoscopic ultrasound 46 8 16.60% 3% 6.1 (2.86 - 13.04) < 0.0001 Sepe 2021 Prospective United States Outpatient clinic Patients who underwent EUS for non-acute hepatobiliary indication 53.6 62.9 ± 13.9 Endoscopic ultrasound 52 NA Endoscopic ultrasound 27 NA 51.95% NR NR NR Sezgin 2022 Prospective Turkey Outpatient clinic Adults attending the GI Clinic for a medical check up 61.60% 43.51 ± 16.66 Abdominal Ultrasound 67 NA Abdominal Ultrasound 50 NA 74.62% NR NR NR Ulasoglu 2021 Cross-sectional study Turkey Outpatient clinic Dyspeptic patients referred for abdominal ultrasound 63.7 52±15 Abdominal Ultrasound 219 NA Abdominal Ultrasound 175 NA 79.90% NR NR NR Uygun 2015 Case-Control Study United States Outpatient clinic Adults with known NAFLD and healthy controls 26 37.9 ± 1.3 Abdominal Ultrasound 84 NA Abdominal Ultrasound 43 NA 51.10% NR NR NR Wang 2018 Cross-sectional study China Outpatient clinic Adults without pancreatic, liver or kidney disease 52.9 45 ± 14 Abdominal Ultrasound 363 NA Abdominal Ultrasound 38 NA 10.40% NR NR NR Weng 2018 Cross-sectional study China Outpatient clinic Adults undergoing health screening 48.7 NA Abdominal Ultrasound 1116 NA Abdominal Ultrasound 301 NA 26.90% NR NR NR Figure 1.: (A) Forest plot of pooled prevalence of NAFPD in patients with NAFLD. (B) Forest plot of odds ratio for NAFPD, comparing NAFLD population and control groups.