Metabolic-associated fatty liver disease is associated with acute pancreatitis with more severe course: Post hoc analysis of a prospectively collected international registry.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP. METHODS: We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis. RESULTS: MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant. CONCLUSIONS: MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP.

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Early prediction of acute necrotizing pancreatitis by artificial intelligence: a prospective cohort-analysis of 2387 cases.

Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently in use are either too complicated or require data that are unavailable on admission or lack sufficient predictive value. We therefore aimed to develop a tool to aid in necrosis prediction. The XGBoost machine learning algorithm processed data from 2387 patients with AP. The confidence of the model was estimated by a bootstrapping method and interpreted via the 10th and the 90th percentiles of the prediction scores. Shapley Additive exPlanations (SHAP) values were calculated to quantify the contribution of each variable provided. Finally, the model was implemented as an online application using the Streamlit Python-based framework. The XGBoost classifier provided an AUC value of 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender and total white blood cell count have the most impact on prediction based on the SHAP values. The relationship between the size of the training dataset and model performance shows that prediction performance can be improved. This study combines necrosis prediction and artificial intelligence. The predictive potential of this model is comparable to the current clinical scoring systems and has several advantages over them.

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.

Early occurrence of pseudocysts in acute pancreatitis - A multicenter international cohort analysis of 2275 cases.

BACKGROUND: Pseudocysts being the most frequent local complications of acute pancreatitis (AP) have substantial effect on the disease course, hospitalization and quality of life of the patient. Our study aimed to understand the effects of pre-existing (OLD-P) and newly developed (NEW-P) pseudocysts on AP. METHODS: Data were extracted from the Acute Pancreatitis Registry organized by the Hungarian Pancreatic Study Group (HPSG). 2275 of 2461 patients had uploaded information concerning pancreatic morphology assessed by imaging technique. Patients were divided into "no pseudocyst" (NO-P) group, "old pseudocyst" (OLD-P) group, or "newly developed pseudocyst" (NEW-P) groups. RESULTS: The median time of new pseudocyst development was nine days from hospital admission and eleven days from the beginning of the abdominal pain. More NEW-P cases were severe (15.9% vs 4.7% in the NO-P group p < 0.001), with longer length of hospitalization (LoH) (median: 14 days versus 8 days, p < 0.001), and were associated with several changed laboratory parameters. OLD-P was associated with male gender (72.2% vs. 56.1%, p = 0.0014), alcoholic etiology (35.2% vs. 19.8% in the NO-P group), longer hospitalization (median: 10 days, p < 0.001), a previous episode of AP (p < 0.001), pre-existing diagnosis of chronic pancreatitis (CP) (p < 0.001), current smoking (p < 0.001), and increased alcohol consumption (unit/week) (p = 0.014). CONCLUSION: Most of the new pseudocysts develop within two weeks. Newly developing pseudocysts are associated with a more severe disease course and increased length of hospitalization. Pre-existing pseudocysts are associated with higher alcohol consumption and smoking. Because CP is more frequently associated with a pre-existing pseudocyst, these patients need closer attention after AP.

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model.

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (<1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, ≥22.6 mmol/l). RESULTS: Hypertriglyceridemia (≥1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (≥11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. CONCLUSION: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP.

Multiple Hits in Acute Pancreatitis: Components of Metabolic Syndrome Synergize Each Other's Deteriorating Effects.

INTRODUCTION: The incidence of acute pancreatitis (AP) and the prevalence of metabolic syndrome (MetS) are growing worldwide. Several studies have confirmed that obesity (OB), hyperlipidemia (HL), or diabetes mellitus (DM) can increase severity, mortality, and complications in AP. However, there is no comprehensive information on the independent or joint effect of MetS components on the outcome of AP. Our aims were (1) to understand whether the components of MetS have an independent effect on the outcome of AP and (2) to examine the joint effect of their combinations. METHODS: From 2012 to 2017, 1435 AP cases from 28 centers were included in the prospective AP Registry. Patient groups were formed retrospectively based on the presence of OB, HL, DM, and hypertension (HT). The primary endpoints were mortality, severity, complications of AP, and length of hospital stay. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: 1257 patients (55.7 ± 17.0 years) were included in the analysis. The presence of OB was an independent predictive factor for renal failure [OR: 2.98 (CI: 1.33-6.66)] and obese patients spent a longer time in hospital compared to non-obese patients (12.1 vs. 10.4 days, p = 0.008). HT increased the risk of severe AP [OR: 3.41 (CI: 1.39-8.37)], renal failure [OR: 7.46 (CI: 1.61-34.49)], and the length of hospitalization (11.8 vs. 10.5 days, p = 0.020). HL increased the risk of local complications [OR: 1.51 (CI: 1.10-2.07)], renal failure [OR: 6.4 (CI: 1.93-21.17)], and the incidence of newly diagnosed DM [OR: 2.55 (CI: 1.26-5.19)]. No relation was found between the presence of DM and the outcome of AP. 906 cases (mean age ± SD: 56.9 ± 16.7 years) had data on all four components of MetS available. The presence of two, three, or four MetS factors increased the incidence of an unfavorable outcome compared to patients with no MetS factors. CONCLUSION: OB, HT, and HL are independent risk factors for a number of complications. HT is an independent risk factor for severity as well. Components of MetS strongly synergize each other's detrimental effect. It is important to search for and follow up on the components of MetS in AP.

A Multicenter, International Cohort Analysis of 1435 Cases to Support Clinical Trial Design in Acute Pancreatitis.

BACKGROUND: C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role. METHODS: First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 h from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U, Levene's F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed. RESULTS: Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC: 0.669 (CI:0.569-0.770); AUC:0.681 (CI: 0.601-0.761), respectively. CRP levels measured within 24 h from the onset of pain failed to predict mortality or severity; AUC: 0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 h from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP > 25 mg/l and 28% for CRP > 200 mg/l). CONCLUSION: CRP within 24 h from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP.

Changes in the Velocity of Blood in the Portal Vein in Mild Acute Pancreatitis-A Preliminary Clinical Study.

Background and objective: Portal vein thrombosis is associated with a decrease in the main blood velocity in this vessel. While most studies examine etiological factors of portal vein thrombosis after its occurrence, we aimed to evaluate portal vessels and assess whether mild acute pancreatitis affects blood flow in the portal vein and increases the risk of thrombosis. Materials and methods: This prospective single centered follow-up study enrolled 66 adult participants. Fifty of them were diagnosed with mild acute pancreatitis based on the Revised Atlanta classification, and 16 healthy participants formed the control group. All participants were examined three times. The first examination was carried out at the beginning of the disease and the next two at three-month intervals. Blood samples were taken and color Doppler ultrasound performed the first time, whereas ultrasound alone was performed during the second and third visits. Mean and maximal blood velocities and resistivity index in the main portal vein and its left and right branches were evaluated. Results: Mean velocity of the blood flow in the main portal vein and its right and left branches was not significantly different from healthy individuals during the acute pancreatitis phase: 23.1 ± 8.5 cm/s vs. 24.5 ± 8.2 cm/s (p = 0.827); 16.4 ± 7.9 cm/s vs. 16.4 ± 8.1 cm/s (p = 1.000); and 8 ± 3.4 cm/s vs. 7.4 ± 2.5 cm/s (p = 0.826), respectively. The same was observed when comparing the maximal blood flow velocity: 67.9 ± 29 cm/s vs. 67.5 ± 21 cm/s (p > 0.05); 45.4 ± 27 cm/s vs. 44 ± 23.8 cm/s (p = 0.853); and 22.2 ± 9.8 cm/s vs. 20 ± 7.3 cm/s (p = 0.926), respectively. Changes in venous blood velocities were not significant during the follow-up period in separate study groups. Conclusions: Portal blood flow velocities do not change during mild acute pancreatitis in the inflammatory and postinflammatory periods. This observation suggests that mild acute pancreatitis does not increase the risk of portal vein thrombosis.

Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis.

Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28). The serum inflammatory profile was assessed using an MSD 30-plex array. The relationship between clinical variables, inflammatory cytokines and quality of life was determined by a GLM-MANOVA and the individual impact of significant variables evaluated by a second ANOVA. In total, 211 patients with a median age of 53 years were recruited across 5 European centres. Gender, age, nicotine and alcohol abuse were clinical variables associated with altered quality of life. Systemic inflammation with high levels of pro-inflammatory cytokines (Eotaxin, IL-1ß, IL-7, IL-8, IL-12/IL-23p40, IL-12p70, IL-13, IL-16, IP-10, MCP-1, MCP-4, MDC, MIP-1a, TARC, TNFß) was associated with diminished quality of life in general and specific domains including pain, physical and cognitive functioning. As conclusion, CP is associated with a systemic inflammatory response that has a negative impact on quality of life and accelerates aging.

Chronic pancreatitis: Do serum biomarkers provide an association with an inflammageing phenotype?

BACKGROUND: Chronic pancreatitis is an inflammatory disorder of the pancreas that is associated with accelerated mortality for patients suffering from this disease. The association between chronic inflammation and accelerated biological ageing has been well described and is often referred to as "inflammageing". In this review we seek to determine how systemic inflammation in chronic pancreatitis may contribute to an accelerated ageing phenotype. METHODS: A systematic literature search with a predefined search protocol was performed on Medline, Embase and Cochrane libraries according to the PRISMA guidelines. RESULTS: The initial search identified 499 studies. After title, abstract and full text screen of the search results, 20 were included for further evaluation. In the 20 remaining articles 41 inflammatory mediators were identified - mainly involved in chronic inflammation, fibrosis and particularly cardinal features of inflammageing such as sarcopenia and osteoporosis. CONCLUSION: Chronic pancreatitis is associated with elevated levels of inflammatory mediators many of which are associated with an accelerated ageing phenotype and may explain some of the clinical sequelae of this disease.