Rising global trends in obesity have led to increased prevalence of fatty liver disease known as nonalcoholic fatty liver disease (NAFLD). The previously used, stigma-associated term has been replaced by updated nomenclature—first, metabolic dysfunction–associated fatty liver disease (MAFLD) and subsequently metabolic dysfunction–associated steatotic liver disease (MASLD). This modification reflects a more accurate understanding of disease pathophysiology and removes the emphasis from severe alcohol consumption, while introducing diagnostic criteria centered on metabolic dysfunction. This review also describes related clinical entities like metabolic dysfunction–associated steatohepatitis (MASH) and steatotic liver disease (SLD). Global trends in obesity indicate a continuous rise in prevalence, accompanied by an increasing burden of SLD in both adults and pediatric population. Projections suggest that by 2040, more than half of the global population may be affected by both obesity and SLD, highlighting the need for non-invasive diagnostics, effective targeted therapy and structured follow up strategies. Drugs for obesity management like semaglutide and tirzepatide demonstrated clinical improvement primarily through beneficial metabolic effect, highlighting common basis of treatment of obesity and SLD. Although several liver-targeted therapies are currently under investigation, resmetirom represents the first approved pharmacologic agent available on the market. However, lifestyle modification remains significant part of treatment. Looking ahead, field of greatest potential is pharmacotherapy with certain molecules currently under phase 2 and phase 3 clinical trials. Importantly, shared pathophysiologic mechanisms linking obesity, metabolic syndrome and MASLD must not be overlooked in suspicion, diagnosis and treatment of liver diseases.

BACKGROUND:Clinically significant portal hypertension (CSPH) in chronic liver disease (CLD) is a key driver of decompensation, with severe portal hypertension (SPH) leading to severe complications like oesophageal bleeding. Early detection is essential for timely treatment. The current gold standard for assessing portal pressure is hepatic venous pressure gradient (HVPG), an invasive and costly procedure with limited availability. Non-invasive alternatives are increasingly needed to estimate portal pressure (e.g. by liver and spleen stiffness measurement) and guide treatment. However, the diagnostic accuracy of vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) remains unknown. OBJECTIVES:Primary objectives: to assess the diagnostic accuracy of liver stiffness measurement (LSM) and spleen stiffness measurement (SSM), as well as in combination, measured by any elastography technique (VCTE, pSWE, 2D-SWE, or MRE) in the detection of CSPH in adults with CLD; and to compare the diagnostic accuracies between the individual tests. We will regard a combination of tests as positive when at least one is positive. SECONDARY OBJECTIVES:to assess the diagnostic accuracy of LSM and SSM, as well as in combination, measured by any elastography technique (VCTE, pSWE, 2D-SWE, or MRE) in the detection of SPH in adults with CLD; and to investigate sources of heterogeneity in the results. SEARCH METHODS:We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test of Accuracy Studies Register, CENTRAL, MEDLINE ALL Ovid, Embase Ovid, LILACS, Science Citation Index - Expanded (Web of Science), and Conference Proceedings Citation Index - Science (Web of Science) until 8 April 2024. We applied no restrictions on language or document type. SELECTION CRITERIA:We included studies that evaluated the diagnostic accuracy of LSM and SSM either alone or in combination, as measured by different elastography techniques (VCTE, pSWE, 2D-SWE, or MRE), for the diagnosis of CSPH and SPH in adults with CLD. We only considered studies with cross-sectional design using HVPG measurement as the reference standard. DATA COLLECTION AND ANALYSIS:Two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-C tool. In the case of different cut-off values, we used the hierarchical summary receiver operating characteristic (HSROC) model to meta-analyse data (sensitivities and specificities) and to estimate a summary ROC (SROC) curve. In the case of common cut-off values, we used the bivariate model. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS:We included 47 studies (7817 participants). The most evaluated index test was LSM by VCTE for CSPH (27 studies; 3818 participants). We judged only two studies at low risk of bias for all domains. Most showed high risk in the index test domain due to lack of prespecified thresholds and high concern for applicability in patient selection. Overall, the certainty of evidence was very low. Due to varying thresholds across studies, we used an HSROC model to obtain summary estimates. The main findings for detecting CSPH are below. LSM by VCTE (27 studies, 3818 participants): Sensitivity 72.6% (95% CI 60.0% to 82.5%) at fixed specificity of 90% Specificity 75.9% (95% CI 63.5% to 85.1%) at fixed sensitivity of 90% SSM by VCTE (6 studies, 391 participants): Sensitivity 72.9% (95% CI 27.1% to 95.1%) at fixed specificity of 90% Specificity 80.6% (95% CI 64.1% to 90.7%) at fixed sensitivity of 90% SSM by pSWE (4 studies, 248 participants): Sensitivity 84.1% (95% CI 8.4% to 99.7%) at fixed specificity of 90% Specificity 86.1% (95% CI 40.4% to 98.3%) at fixed sensitivity of 90% LSM by 2D-SWE (10 studies, 767 participants): Sensitivity 73.5% (95% CI 52.6% to 87.4%) at fixed specificity of 90% Specificity 83.4% (95% CI 68.2% to 92.2%) at fixed sensitivity of 80% (estimation at 90% not feasible) SSM by 2D-SWE (6 studies, 353 participants): Sensitivity 80.0% (95% CI 59.8% to 91.5%) at fixed specificity of 90% Estimation at fixed sensitivity not feasible HSROC analysis was not feasible for LSM by pSWE and LSM or SSM by MRE due to insufficient data. For LSM by VCTE at 25 kPa (9 studies, 1553 participants), sensitivity was 62.3% (95% CI 53.0% to 70.7%) and specificity 94.1% (95% CI 87.2% to 97.3%). We explored heterogeneity and observed a prevalence effect: relative specificity 0.90 (95% CI 0.83 to 0.97). Other factors could not be assessed. For SPH as secondary objective, LSM by VCTE was the most evaluated test (8 studies; 637 participants). Sensitivity corresponding to specificity of 90% was 67.2% (95% CI 48.8% to 81.4%), while specificity corresponding to sensitivity of 90% could not be calculated by the HSROC model. Direct comparisons between two index tests were impossible due to inconsistent numbers of participants included for each index test. Due to variability in cut-off values reported across studies, we only performed indirect comparisons using SROC curves. Thus, no reliable results emerged from comparisons or combinations across techniques. AUTHORS' CONCLUSIONS:Liver and spleen stiffness measurements may offer a non-invasive alternative to HVPG for detecting CSPH. However, the accuracy of individual techniques remains uncertain due to very low-certainty evidence and insufficient data for reliable comparisons. No test achieved both sensitivity and specificity ≥ 90%, limiting their utility for confidently ruling in or out CSPH. For LSM by VCTE, the most commonly studied method, HSROC modelling yielded a sensitivity of 72.6% (95% CI 60.0% to 82.5%) at a fixed specificity of 90%, based on studies using various thresholds. In a subgroup of nine studies (1553 participants) using the predefined 25 kPa cut-off, 38% of patients with CSPH would be missed, and 6% without CSPH would be incorrectly identified. The certainty of the evidence is very low, mainly due to high risk of bias, heterogeneity, and imprecision. High-quality research is needed with predefined thresholds, standardised methodology, and improved reporting. Future studies should target key subpopulations (e.g. compensated CLD, specific aetiologies) and assess combinations of non-invasive tools to enhance diagnostic accuracy and clinical usefulness. FUNDING:No internal or external sources of support. REGISTRATION:https://doi.org/10.1002/14651858.CD015415.

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To assess the diagnostic accuracy of liver stiffness and spleen stiffness, as well as their combination, as measured by vibration‐controlled transient elastography (VCTE) in the detection of clinically significant portal hypertension (CSPH) in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of individual tests (liver and spleen stiffness by VCTE) directly and versus the combination of both tests (liver and spleen stiffness by VCTE considered positive when at least one test is positive) in detecting CSPH. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, as well as their combination, as measured by other elastography techniques (two‐dimensional shear wave elastography (2D‐SWE), point shear wave elastography (pSWE), and magnetic resonance elastography (MRE)) in the detection of CSPH in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of liver stiffness and spleen stiffness by VCTE with other techniques (2D‐SWE, pSWE, MRE) in the detection of CSPH in adults with chronic liver disease. Secondary objectives To assess the diagnostic accuracy of liver stiffness and spleen stiffness, as well as their combination, as measured by VCTE in the detection of severe portal hypertension (SPH) in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, as well as their combination, as measured by the other elastography techniques (2D‐SWE, pSWE, MRE) in the detection of SPH in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of liver stiffness and spleen stiffness by VCTE with other techniques (pSWE, 2D‐SWE, MRE) in the detection of SPH in adults with chronic liver disease. To investigate the following potential sources of heterogeneity in the results of liver stiffness and spleen stiffness, as well as their combination, as measured by VCTE in the detection of CSPH and SPH. Different populations based on the chronic liver disease aetiology, in particular viral compared to non‐viral aetiology: studies including more than 80% of participants with viral aetiology compared to those including less than 80% of participants with viral aetiology. We have chosen a threshold of 80%, as in North America and Europe the prevalence of chronic viral hepatitis is usually lower, whilst in Asia and Africa the prevalence is higher (Wong 2015). Different prevalences of CSPH: studies with prevalence of CSPH > 50% compared to studies with prevalence of CSPH ≤ 50%. We have chosen a threshold of 50% according to a median prevalence of any size oesophageal varices in adults at the diagnosis of cirrhosis (Colli 2014a). Different prevalences of SPH: studies with prevalence of SPH > 25% compared to studies with prevalence of SPH ≤ 25%. We have chosen a threshold of 25% according to a median prevalence of high‐risk oesophageal varices in adults at the diagnosis of cirrhosis (Colli 2014a). Different populations based on the chronic liver disease severity: studies including more than 75% of participants with cirrhosis (Child‐Pugh class A) compared to studies including less than 75% of participants with cirrhosis (Child‐Pugh class A). We have chosen a threshold of 75% according to a median prevalence of adults with cirrhosis in Child‐Pugh class A of 74% in a large cohort study (D'Amico 2014). Type of probe used (liver, [email protected] versus spleen, [email protected]) for spleen stiffness measurement by VCTE. Type of probe used (M versus XL) when liver, [email protected] probe is used for spleen stiffness measurement by VCTE. Number of unsuccessful or indeterminate results to obtain any LSM or SSM: studies with more than 20% compared to studies with less than 20% of unsuccessful or indeterminate results. We have chosen a threshold of 20%, as the test applicability estimated in a large series was 81% (Castéra 2010).

OBJECTIVES:This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To estimate the diagnostic accuracy of des-gamma-carboxy prothrombin, GALAD (Gender, Age, Lens culinaris agglutinin-reactive AFP, AFP and DCP), and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma of any size, and at any stage, in adults with chronic liver disease, in either a surveillance programme or a clinical setting. We acknowledge the possibility that theoretically, the accuracy of the tests in a surveillance programme may differ from that in a clinical setting due to variation in inclusion criteria and the prevalence of the target condition. However, we do not plan a separate analysis for surveillance and clinical settings, as they are not clearly distinct in current clinical practice (Forner 2018; Poustchi 2011). In routine evaluation of people with chronic liver disease, index tests, as well as ultrasound, are already part of standard procedure. Given that HCC typically presents with no symptoms and is often asymptomatic, suspicion of the disease is typically based solely on the presence of advanced chronic liver disease. However, we do plan to consider the study setting as a potential source of heterogeneity. To compare the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP) alone or GALAD alone versus alpha-foetoprotein (AFP), for the diagnosis of hepatocellular carcinoma (HCC) of any size, at any stage; in adults with chronic liver disease, either in a surveillance programme or a clinical setting. Secondary objectives To estimate the diagnostic accuracy of DCP or GALAD versus AFP, for resectable HCC in people with chronic liver disease, in a surveillance programme and a clinical setting. To investigate the following predefined sources of heterogeneity for each of the index tests: study design (case-control studies compared to cross-sectional studies); inclusion of participants without cirrhosis (studies including more than 10% of participants without cirrhosis compared to studies including less than 10% of participants without cirrhosis); study location (population differences): studies conducted in North and South America and Europe compared to Asia and Africa; prevalence of the target condition (studies with hepatocellular carcinoma prevalence more than 10% compared to studies with hepatocellular carcinoma prevalence less than 10%); participant selection (participants recruited from planned surveillance programmes compared to clinical cohorts); different reference standards (histology of the explanted liver compared to liver biopsy compared to another reference standard); different aetiology: studies including at least 90% of participants with chronic viral hepatitis compared to studies including less than 90% of participants with chronic viral hepatitis.

BACKGROUND:Predicting Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis (PEP) risk can be determinant in reducing its incidence and managing patients appropriately, however studies conducted thus far have identified single-risk factors with standard statistical approaches and limited accuracy.AIM:To build and evaluate performances of machine learning (ML) models to predict PEP probability and identify relevant features.METHODS:A proof-of-concept study was performed on ML application on an international, multicenter, prospective cohort of ERCP patients. Data were split in training and test set, models used were gradient boosting (GB) and logistic regression (LR). A 10-split random cross-validation (CV) was applied on the training set to optimize parameters to obtain the best mean Area Under Curve (AUC). The model was re-trained on the whole training set with the best parameters and applied on test set. Shapley-Additive-exPlanation (SHAP) approach was applied to break down the model and clarify features impact.RESULTS:One thousand one hundred and fifty patients were included, 6.1% developed PEP. GB model outperformed LR with AUC in CV of 0.7 vs 0.585 (p-value=0.012). GB AUC in test was 0.671. Most relevant features for PEP prediction were: bilirubin, age, body mass index, procedure time, previous sphincterotomy, alcohol units/day, cannulation attempts, gender, gallstones, use of Ringer's solution and periprocedural NSAIDs.CONCLUSION:In PEP prediction, GB significantly outperformed LR model and identified new clinical features relevant for the risk, most being pre-procedural.

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by vibration‐controlled transient elastography (VCTE) in detection of any oesophageal varices in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of individual tests (liver stiffness and spleen stiffness measured by VCTE) directly and versus the combination of both tests (considering positive when at least one is positive) in detecting any oesophageal varices. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by other elastography techniques (2D‐shear wave elastography (2D‐SWE), point shear wave elastography (pSWE), magnetic resonance elastography (MRE)) in detection of any oesophageal varices in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of liver stiffness and spleen stiffness measured by VCTE with other techniques (pSWE, 2D‐SWE, MRE) in detection of any oesophageal varices in adults with chronic liver disease. Secondary objectives To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by vibration‐controlled transient elastography (VCTE) in detection of high‐risk oesophageal varices (HROVs) in adults with chronic liver disease. We will consider a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of individual tests (liver stiffness and spleen stiffness measured by VCTE) directly and versus the combination of both tests (considering positive when at least one is positive) in detecting HROVs. To assess the diagnostic accuracy of liver stiffness and spleen stiffness, separately or in combination, as measured by other different elastography techniques (2D‐shear wave elastography (2D‐SWE), point shear wave elastography (pSWE), magnetic resonance elastography (MRE)) in detection of HROVs in adults with chronic liver disease. We will regard a combination of tests as positive when at least one is positive. To compare the diagnostic accuracy of liver stiffness and spleen stiffness measured by VCTE with other techniques (pSWE, 2D‐SWE, MRE) in detection of HROVs in adults with chronic liver disease. To investigate potential sources of heterogeneity in the results of liver stiffness and spleen stiffness, separately or in combination, as measured by VCTE, in detection of any oesophageal varices and HROVs.

BACKGROUND Hepatocellular carcinoma occurs mostly in people with chronic liver disease. Worldwide, it ranks sixth in terms of incidence of cancer, and fourth in terms of cancer-related deaths. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma after prior diagnostic tests such as abdominal ultrasound or measurement of alpha-foetoprotein, or both. According to guidelines, a single contrast-enhanced imaging investigation, with either computed tomography (CT) or magnetic resonance imaging (MRI), may show the typical hepatocellular carcinoma hallmarks in people with cirrhosis, which will be sufficient to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas show atypical imaging features, and therefore, are missed at imaging. Dynamic CEUS images are obtained similarly to CT and MRI images. CEUS differentiates between arterial and portal venous phases, in which sonographic hepatocellular carcinoma hallmarks, such as arterial hyperenhancement and subsequent washout appearance, are investigated. The advantages of CEUS over CT and MRI include real-time imaging, use of contrast agents that do not contain iodine and are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival as the conflicting results can be a consequence of an inaccurate detection, ineffective treatment, or both. Therefore, assessing the diagnostic accuracy of CEUS may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CEUS for the diagnosis of hepatocellular carcinoma is needed for either diagnosing hepatocellular carcinoma or ruling it out in people with chronic liver disease who are not included in surveillance programmes. OBJECTIVES 1. To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting. 2. To assess the diagnostic accuracy of CEUS for the diagnosis of resectable hepatocellular carcinoma in people with chronic liver disease and identify potential sources of heterogeneity in the results. SEARCH METHODS We used standard, extensive Cochrane search methods. The last date of search was 5 November 2021. SELECTION CRITERIA We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the characteristics of the participants. - CEUS for hepatocellular carcinoma of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence). - CEUS for resectable hepatocellular carcinoma: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence). The observed heterogeneity in the results remains unexplained. The sensitivity analyses, including only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted with no knowledge of the results about the index test, showed no differences in the results. AUTHORS' CONCLUSIONS We found that by using CEUS, as an add-on test following abdominal ultrasound, to diagnose hepatocellular carcinoma of any size and stage, 22% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would unnecessarily undergo further testing or inappropriate treatment. As to resectable hepatocellular carcinoma, we found that 23% of people with resectable hepatocellular carcinoma would incorrectly be unresected, while 8% of people without hepatocellular carcinoma would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.

Background: Barrett's esophagus (BE) requires surveillance to identify potential neoplasia at an early stage. The standard surveillance regimen includes random 4-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding, and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents a real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1,000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patients. The main advantages would be real-time diagnosis and decision-making, greater diagnostic accuracy, and evaluation of larger area compared to random biopsies. Clinical pCLE studies in the esophagus show high diagnostic accuracy, and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key Messages: Despite promising results, its role in routine use in patients with BE remains questionable primarily due to lack of well-organized double-blind randomized trials.

Obesity is a serious global public health problem. It is a complex disease caused by a combination of several factors including overeating and a sedentary lifestyle, genetic susceptibility and environmental factors. Substantial scientific evidence indicates that increase in obesity prevalence correlates with increase in production and human exposure to environmental chemicals, suggesting that a long list of chemical compounds that can be found all around us may play a role in the etiology of obesity.Endocrine disrupting compounds (EDCs) are chemicals that can interfere with the function of endocrine system. A subclass of EDCs that can disrupt a great number of metabolic processes including normal development of adipose tissue and balance of lipid metabolism thus leading to obesity are called obesogens. They can be found in electronics, plastics, furniture, clothes, cosmetics and also in the air, water and food that people consume. Persistent organophosphate pesticides, flame retardants, nicotine and plastics have all been linked to obesity particularly if exposure occurs during early life (in utero, newborns). Early development is the most vulnerable period for obesogen exposure leading to epigenetic changes that persist throughout life.Current knowledge on obesogens is probably just „the tip of the iceberg“ and future research is needed as well as increasing public awareness of this problem and its implications to human health. It is important to establish control over obesogens and try to prevent or at least limit the exposure of people, especially children and pregnant women, to these dangerous and harmful chemical compounds.

Review team: Lisbeth Mathus-Vliegen, MD, PhD, (co-chair) (The Netherlands), James Toouli, MBBS, FRACS, PhD, (co-chair) (Australia), Michael Fried, MD, (Switzerland), Aamir Ghafoor Khan, MD, (Pakistan), James Garisch, MD, (South Africa), Richard Hunt, MD, (Canada), Suleiman Fedail, MD, FRCP MWGO, (Sudan), Davor Štimac, MD, (Croatia), Ton Lemair, MD, (The Netherlands), Justus Krabshuis, (France), External experts: Pedro Kaufmann, MD, (Uruguay), Eve Roberts, MD, (Canada), and Gabriele Riccardi, MD, (Italy)

We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non‐alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non‐significant or no liver fibrosis.

Background: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet. Methods: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables. Results: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications. Conclusions: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP. (c) 2021 Published by Elsevier B.V. on behalf of IAP and EPC.

Colorectal cancer is a malignant neoplasm which has an increasing incidence and represents a global public health problem. The majority of patients are diagnosed after the age of 50, and the risk of developing it over lifetime is 5%. Development of preventive, diagnostic and treatment methods has resulted in a significant reduction in mortality and other negative clinical outcomes. Precisely because of the efficient method of prevention and early detection of this disease, numerous countries, including Croatia, have organized national colorectal cancer screening and monitoring programs. However, these programs are primarily organized for the population with the usual, i.e. average risk of developing colorectal cancer. High-risk groups include persons with endoscopically detected and removed colon polyps, persons surgically treated for colon cancer, persons with a positive family history of colorectal cancer, persons with inflammatory bowel diseases, individuals and families with hereditary disorders or genetic mutations that increase the risk of this disease several fold, persons with acromegaly, and patients who have undergone ureterosigmoidostomy. Recommendations for the detection and monitoring of high-risk groups are often not defined clearly, and some of the existing ones are based mostly on scarce scientific evidence. It is commonly accepted that screening in high-risk groups should start at an earlier age, with shorter intervals between follow-ups. The basic diagnostic method for screening and monitoring in these patient groups is endoscopic monitoring, or colonoscopy. The aim of this review paper is to present the characteristics of the abovementioned risk groups and provide clear screening recommendations.

Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at an early stage. The standard surveillance regimen includes random 4-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding, and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents a real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1,000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patients. The main advantages would be real-time diagnosis and decision-making, greater diagnostic accuracy, and evaluation of larger area compared to random biopsies. Clinical pCLE studies in the esophagus show high diagnostic accuracy, and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key Messages: Despite promising results, its role in routine use in patients with BE remains questionable primarily due to lack of well-organized double-blind randomized trials.

Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP.

BACKGROUNDHepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and third in terms of cancer deaths. In clinical practice, magnetic resonance imaging (MRI) is used as a second-line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha-fetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast-enhanced imaging study (computed tomography (CT) or MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is considered valid to diagnose hepatocellular carcinoma. The detection of hepatocellular carcinoma amenable to surgical resection could improve the prognosis. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma may, therefore, be missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of MRI may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of MRI in people with chronic liver disease who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma.OBJECTIVESPrimary: to assess the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease. Secondary: to assess the diagnostic accuracy of MRI for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease, and to identify potential sources of heterogeneity in the results.SEARCH METHODSWe searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test of Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, and three other databases to 9 November 2021. We manually searched articles retrieved, contacted experts, handsearched abstract books from meetings held during the last 10 years, and searched for literature in OpenGrey (9 November 2021). Further information was requested by e-mails, but no additional information was provided. No data was obtained through correspondence with investigators. We applied no language or document-type restrictions.SELECTION CRITERIAStudies assessing the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six-month follow-up.DATA COLLECTION AND ANALYSISAt least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and we tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses.MAIN RESULTSWe included 34 studies, with 4841 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time interval between the index test and the reference standard was rarely defined. Regarding applicability, we judged 15% (5/34) of studies to be at low concern and 85% (29/34) of studies to be at high concern mostly owing to characteristics of the participants, most of whom were on waiting lists for orthotopic liver transplantation, and due to pathology of the explanted liver being the only reference standard. MRI for hepatocellular carcinoma of any size and stage: sensitivity 84.4% (95% CI 80.1% to 87.9%) and specificity 93.8% (95% CI 90.1% to 96.1%) (34 studies, 4841 participants; low-certainty evidence). MRI for resectable hepatocellular carcinoma: sensitivity 84.3% (95% CI 77.6% to 89.3%) and specificity 92.9% (95% CI 88.3% to 95.9%) (16 studies, 2150 participants; low-certainty evidence). The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results.AUTHORS' CONCLUSIONSWe found that using MRI as a second-line imaging modality to diagnose hepatocellular carcinoma of any size and stage, 16% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 16% of people with resectable hepatocellular carcinoma would improperly not be resected, while 7% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP >= 345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F >= F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (beta = 2.6, p < 0.001) as a positive predictor and lobular inflammation (beta = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis. (E-mail: ivana.mikolasevic@gmail.com) (c) 2020 World Federation for Ultrasound in Medicine & Biology. All rights reserved.