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Background Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients. Methods We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality. Discussion If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future. Trial registration : ClinicalTrials.gov Identifier: NCT04777812

Background ALT value is often used to reflect the hepatic inflammation and injury in NAFLD patients, but many studies proved that ALT values were normal in many NAFLD patients. The aim of this study was to identify the summarized proportion of NAFLD patients with normal ALT value in the overall NAFLD patients. Methods Electronic databases PubMed, EMBASE, Ovid, and the Cochrane Library were searched for potential studies published from January 1, 2000 to September 30, 2019. Studies that have reported the number of NAFLD or NASH patients with normal and abnormal ALT value were included and analyzed. Abstracts, reviews, case reports, and letters were excluded. Results A total of 11 studies with 4084 patients were included for assessing the summarized proportion of NAFLD patients with normal ALT in overall NAFLD patients. As the results shown, the summarized proportion of NAFLD patients with normal ALT value in overall NAFLD patients was 25% (95%CI: 20–31%) which was calculated by the random-effects model. The summarized proportion of NASH patients with normal ALT value in overall NASH patients was 19% (95%CI: 13–27%). Subgroup analysis includes region, study type, diagnostic method, and group size were conducted to investigate the resource of heterogeneity in the summarized proportion of NAFLD and NASH patients with normal ALT value. Conclusions 25% NAFLD patients and 19% NASH patients possess the normal ALT value in the clinical manifestation. The value of ALT in the clinical diagnosis of NAFLD and NASH remains need be further testified.

Background Previous studies have demonstrated that endoscopic ultrasound-fine needle aspiration (EUS-FNA) is a reliable tool for diagnosing pancreatic lesions; however, the reported sensitivity and specificity vary greatly across studies. The aim of this study was to pool the existing literature and assess the overall performance of EUS-FNA in the diagnosis of solid pancreatic lesions. Methods A systematic search of MEDLINE, Cochrane Database for Systematic Reviews, and EMBASE was performed to identify original and review articles published between January 1995 and January 2014 that reported the accuracy of EUS-FNA in the diagnosis of pancreatic masses. Quality of the included studies was assessed using the quality assessment of diagnosis accuracy studies score tool. Meta-DiSc software was used to calculate the pooled sensitivity and specificity, positive and negative likelihood ratios, and to construct the summary receiver operating characteristics curve. Results Twenty studies involving a total of 2,761 patients were included in the study. The pooled sensitivity and specificity of EUS-FNA in the diagnosis of solid pancreatic lesions were 90.8 % [95 % confidence interval (CI), 89.4–92 %] and 96.5 % (95 % CI, 94.8–97.7 %), respectively. The positive and negative likelihood ratios were 14.8 (95 % CI, 8.0–27.3) and 0.12 (95 % CI, 0.09–0.16), respectively. The overall diagnostic accuracy was 91.0 %. Conclusions Our findings suggest that EUS-FNA has high sensitivity and specificity in the diagnosis of solid pancreatic lesions.

Background Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis. Despite good diagnostic performance, clinical application of CAP is limited due to the influences of covariates. Here, a systematic review on the performance of CAP in the diagnosis and staging of hepatic steatosis in NAFLD patients was performed. Methods The sensitivity, specificity, diagnostic odds ratio (DOR) and area under receiver operating characteristics (AUROC) curves of the pooled data for CAP in diagnosing and staging the mild (Stage 1), moderate (Stage 2) and severe (Stage 3) steatosis in NAFLD patients were assessed. The clinical utility of CAP was evaluated by Fagan plot. Heterogeneity was explored using subgroup analysis. Results Nine studies involving 1297 patients with liver biopsy-proven NAFLD were analyzed. The pooled sensitivity of CAP in detecting mild hepatic steatosis was 87% with a specificity of 91% and a DOR of 84.35. The pooled sensitivity of CAP in detecting moderate hepatic steatosis was 85% with a specificity of 74% and a DOR of 21.28. For severe steatosis, the pooled sensitivity was 76% with a specificity of 58% and a DOR of 4.70. The mean AUROC value for CAP in the diagnosis of mild, moderate, and severe steatosis was 0.96, 0.82 and 0.70, respectively. A subgroup analysis indicated that variation in the geographic regions, cutoffs, age and body mass index (BMI) could be the potential sources of heterogeneity in the diagnosis of moderate to severe steatosis. Conclusions CAP should be cautiously considered as a non-invasive substitute for liver biopsy in clinical practice.

Background Animal models of non-alcoholic steatohepatitis (NASH) are important tools in preclinical research and drug discovery. Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represent a model of fibrosing NASH. The present study directly assessed the clinical translatability of the model by head-to-head comparison of liver biopsy histological and transcriptome changes in GAN DIO-NASH mouse and human NASH patients. Methods C57Bl/6 J mice were fed chow or the GAN diet rich in saturated fat (40%), fructose (22%) and cholesterol (2%) for ≥38 weeks. Metabolic parameters as well as plasma and liver biomarkers were assessed. Liver biopsy histology and transcriptome signatures were compared to samples from human lean individuals and patients diagnosed with NASH. Results Liver lesions in GAN DIO-NASH mice showed similar morphological characteristics compared to the NASH patient validation set, including macrosteatosis, lobular inflammation, hepatocyte ballooning degeneration and periportal/perisinusoidal fibrosis. Histomorphometric analysis indicated comparable increases in markers of hepatic lipid accumulation, inflammation and collagen deposition in GAN DIO-NASH mice and NASH patient samples. Liver biopsies from GAN DIO-NASH mice and NASH patients showed comparable dynamics in several gene expression pathways involved in NASH pathogenesis. Consistent with the clinical features of NASH, GAN DIO-NASH mice demonstrated key components of the metabolic syndrome, including obesity and impaired glucose tolerance. Conclusions The GAN DIO-NASH mouse model demonstrates good clinical translatability with respect to the histopathological, transcriptional and metabolic aspects of the human disease, highlighting the suitability of the GAN DIO-NASH mouse model for identifying therapeutic targets and characterizing novel drug therapies for NASH.

Background The identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies. Methods A probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected. Results Introduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively. The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline. Conclusion Our analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.

Background Nutrition is a modifiable risk factor that plays an important role in the prevention or delaying of the onset of non-alcoholic fatty liver disease (NAFLD). Previous studies have focused on NAFLD and individual nutrients, which does not take into account combinations of food that are consumed. Therefore, we aimed to investigate the relationship between major dietary patterns and NAFLD. Methods This case–control study was conducted on 225 newly diagnosed NAFLD patients and 450 healthy controls. Usual dietary intake over the preceding year was assessed using a validated 168-item semi-quantitative food frequency questionnaire. Major dietary patterns were determined by exploratory factor analysis. Results Three dietary patterns, including \"western dietary pattern\", \"healthy dietary pattern\", and \"traditional dietary pattern\" were identified. Subjects in the highest tertile of healthy dietary pattern scores had a lower odds ratio for NAFLD than those in the lowest tertile. Compared with those in the lowest tertile, people in the highest tertile of “western dietary pattern” scores had greater odds for NAFLD. After adjusting for potential confounding factors, “western dietary pattern” had a positive significant effect on NAFLD occurrence. In contrast, “healthy dietary pattern” was associated with a decreased risk of NAFLD. Furthermore, Higher consumption of the “traditional dietary pattern” was significantly associated with NAFLD, albeit in the crude model only. Conclusion This study indicated that healthy and western dietary patterns may be associated with the risk of NAFLD. The results can be used for developing interventions in order to promote healthy eating for the prevention of NAFLD.

Background Non-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA). Methods A search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics. Results Seven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36–2.79, I 2 =76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52–3.24, I 2 =67%) and 1.55 (95%CI: 1.03–2.33, I 2 =69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41–2.75, I 2 =71%), 2.09 (95%CI, 1.49–2.91, I 2 =42%) and 2.05 (95%CI, 1.59–2.64, I 2 =0%) for all CCAs, iCCA, and eCCA, respectively. Conclusions This meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted. Trial registration The protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).

Background The gold standard for the diagnosis of liver fibrosis and nonalcoholic fatty liver disease (NAFLD) is liver biopsy. Various noninvasive modalities, e.g., ultrasonography, elastography and clinical predictive scores, have been used as alternatives to liver biopsy, with limited performance. Recently, artificial intelligence (AI) models have been developed and integrated into noninvasive diagnostic tools to improve their performance. Methods We systematically searched for studies on AI-assisted diagnosis of liver fibrosis and NAFLD on MEDLINE, Scopus, Web of Science and Google Scholar. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic odds ratio (DOR) with their 95% confidence intervals (95% CIs) were calculated using a random effects model. A summary receiver operating characteristic curve and the area under the curve was generated to determine the diagnostic accuracy of the AI-assisted system. Subgroup analyses by diagnostic modalities, population and AI classifiers were performed. Results We included 19 studies reporting the performances of AI-assisted ultrasonography, elastrography, computed tomography, magnetic resonance imaging and clinical parameters for the diagnosis of liver fibrosis and steatosis. For the diagnosis of liver fibrosis, the pooled sensitivity, specificity, PPV, NPV and DOR were 0.78 (0.71–0.85), 0.89 (0.81–0.94), 0.72 (0.58–0.83), 0.92 (0.88–0.94) and 31.58 (11.84–84.25), respectively, for cirrhosis; 0.86 (0.80–0.90), 0.87 (0.80–0.92), 0.85 (0.75–0.91), 0.88 (0.82–0.92) and 37.79 (16.01–89.19), respectively; for advanced fibrosis; and 0.86 (0.78–0.92), 0.81 (0.77–0.84), 0.88 (0.80–0.93), 0.77 (0.58–0.89) and 26.79 (14.47–49.62), respectively, for significant fibrosis. Subgroup analyses showed significant differences in performance for the diagnosis of fibrosis among different modalities. The pooled sensitivity, specificity, PPV, NPV and DOR were 0.97 (0.76–1.00), 0.91 (0.78–0.97), 0.95 (0.87–0.98), 0.93 (0.80–0.98) and 191.52 (38.82–944.81), respectively, for the diagnosis of liver steatosis. Conclusions AI-assisted systems have promising potential for the diagnosis of liver fibrosis and NAFLD. Validations of their performances are warranted before implementing these AI-assisted systems in clinical practice. Trial registration : The protocol was registered with PROSPERO (CRD42020183295).

Background The prevalence and outcomes of non-alcoholic fatty liver disease (NAFLD) among elderly have not been well described. Our aim was to assess the prevalence, risk factors and mortality of NAFLD in individuals older than 60 years. Methods The data from the Third National Health and Nutrition Examination Survey with linked mortality files were utilized. NAFLD was defined by United States Fatty Liver Index in the absence of other causes of liver disease. Cox proportional hazards models were used to assess all-cause and cardiovascular (CV) mortality. All analyses were performed using SAS software. Results Three thousand two hundred seventy-one NHANES-III participants were included. The prevalence rates from NAFLD were 40.3% (95% CI: 37.2–43.5%) and 39.2% (95% CI: 34.4–44.0%) among 60–74 and > 74 years old. Among aged 60–74, the risks for 5-year and 10-year all-cause mortality were associated with presence of NAFLD [adjusted hazard ratios: 1.60 (95% CI: 1.24–1.96) for 5-year and 1.22 (95%CI: 1.01–1.49) for 10-year]. CV mortality were higher in this group were (aHR: 2.12 (95% CI: 1.20–3.75) for 5-year and 1.06 (95%CI: 0.73–1.52) for 10-year]. In contrast, in individuals > 74 years old, diagnosis of NAFLD was not associated with all-cause or CVD mortality. Conclusions NAFLD is common among elderly population. Although NAFLD is associated with increased risk of mortality for 60–74-year-old individuals, this risk was not increased in those older than 74 years.