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Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as ‘Metabolic dysfunction-Associated Fatty Liver Disease’ (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only – as expected – liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form – nonalcoholic/metabolic dysfunction-associated steatohepatitis – to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.

Cholangioscopy has improved the management of complex biliary diseases; however, digital single‐operator cholangioscopy (DSOC) still faces key limitations, especially in treating intrahepatic disease like hepatolithiasis and strictures, which often require surgery with significant mortality risk. This video case report illustrates the successful endoscopic treatment of an elderly woman with multiple left intrahepatic duct stones and a benign stricture. A next‐generation 11‐Fr high‐definition cholangioscope (VedVision) was employed, offering enhanced imaging, improved maneuverability, and a dual‐channel system enabling simultaneous guidewire and lithotripsy probe use. Electrohydraulic lithotripsy achieved complete stone clearance. A balloon‐expandable biodegradable stent (UNITY‐B), composed of magnesium alloy with polymer coating, was placed across the stricture to reshape it. Subsequent cholangioscopy confirmed correct positioning. This approach highlights a promising, non‐surgical strategy for managing benign intrahepatic biliary disease. The biodegradable stent eliminates the need for removal, reducing the need for further interventions. However, long‐term data and larger studies are necessary to confirm its safety and efficacy.

Background: Contrast-enhanced computed tomography (CECT) is considered the gold standard for assessing therapeutic response in hepatocellular carcinoma (HCC) following locoregional treatments. More recently, contrast-enhanced ultrasound (CEUS) has emerged as a promising, cost-effective alternative, although evidence supporting its use in this context remains limited. This study aimed to evaluate the diagnostic performance of CEUS compared to CECT in assessing local response of HCC nodules treated with radiofrequency ablation (RFA). Methods: We retrospectively analyzed a consecutively enrolled cohort of patients undergoing RFA for HCC at IRCCS San Matteo Hospital, Pavia, between January 2017 and January 2022. Follow-up imaging included both CEUS and CECT at predefined time points. Imaging follow-up, MRI, and/or histological results were used as the reference standard to compare CEUS and CECT. Results: A total of 55 patients (mean age 74 years, 64% male) with 79 HCC nodules were included. Complete response was observed in 57 nodules (72%), all correctly identified by CEUS, whereas 4 cases were misclassified by CECT. Among the 22 nodules (28%) with residual disease, CEUS correctly identified 15 cases, while 17 were detected by CECT; notably, CEUS identified 4 lesions missed by CECT, which identified 6 missed at CEUS. Combined, the two modalities detected 21 (96%) out of 22 residual tumors. CEUS showed a sensitivity of 68.1%, specificity of 100%, and diagnostic accuracy of 91.1%, compared to 68.0%, 98.1%, and 88.6%, respectively, for CECT, with no significant differences. Conclusions: CEUS is a reliable, non-inferior, and complementary modality to CECT for evaluating treatment response of HCC following RFA. Larger prospective studies are warranted to further define its role in clinical practice.

Introduction: High-quality colonoscopy is influenced by several factors, with the adenoma detection rate (ADR) being one of the most studied indicators. A strong inverse relationship exists between ADR and the risk of developing post-colonoscopy colorectal cancer (PCCRC), prompting the European Society of Gastrointestinal Endoscopy guidelines to recommend a minimum ADR of 25%. In contrast, there is limited evidence supporting the clinical significance of the serrated polyp detection rate (SPDR), and no specific benchmark was established until a very recent update from the American societies. Main paper: This review examines the factors that influence ADR and SPDR, offering tips to improve these metrics. Effective interventions for enhancing ADR include training, colonoscopy feedback, adequate bowel preparation, longer withdrawal time, water-aided colonoscopy, right colon second look, and chromoendoscopy. The use of cap, devices, and specialized scopes also show promise, though these are often at higher costs. Artificial intelligence has generated great optimism, especially following positive results from early randomized controlled trials; however, its effectiveness has been less pronounced in real-world settings. Conclusions: Many of these approaches require further trials and meta-analyses to establish their ultimate efficacy. Moreover, future clinical head-to-head studies will help to identify the most effective interventions for reducing colorectal cancer incidence and the risk of PCCRC.

Choledochal cysts (CCs) are cystic dilations of intrahepatic and/or extrahepatic bile ducts. Around 80% of CCs are diagnosed within the first decade of life. These complex clinical entities are extremely rare, especially in the Western population. CCs are frequently classified according to the Todani classification. CCs may be asymptomatic or present as acute pancreatitis and/or cholangitis, biliary obstruction, or malignancy. Therefore, the diagnosis relies primarily on abdominal imaging modalities, mainly magnetic resonance cholangiopancreatography. Management is tailored based on the cyst morphology and the patient’s clinical characteristics, with surveillance, surgery, and interventional endoscopy being the most frequent management options. While the surgical approach is the most frequently employed, type III CCs (also known as choledochocele) are frequently managed endoscopically, and novel endoscopic, minimally invasive treatment options are rapidly emerging.

INTRODUCTION:Patients with type 2 diabetes mellitus (T2DM) are at increased risk of metabolic dysfunction-associated steatotic liver disease, advanced liver fibrosis, and metabolic dysfunction-associated steatohepatitis (MASH). We evaluated the prevalence and severity of metabolic dysfunction-associated steatotic liver disease among patients with T2DM at their first referral to diabetes clinics and assessed the effectiveness of the 2-tier screening approach by Fibrosis-4 (FIB-4) and vibration-controlled transient elastography (VCTE).METHODS:Consecutive patients with T2DM from 6 different diabetes clinics were prospectively enrolled. Liver stiffness measurement (LSM) was assessed by VCTE, whereas liver steatosis by controlled attenuation parameter (Fibroscan, Echosens, France). “At-risk MASH” was assessed by FibroScan-aspartate aminotransferase score.RESULTS:Eight hundred patients (median age: 59, 53–65 years; males: 485, 60.6%) met the inclusion criteria. Prevalence of liver steatosis (controlled attenuation parameter ≥ 248 db/m) was 73.6%. The proportion of patients at medium/high risk of advanced liver fibrosis (LSM ≥ 8.0 kPa) was 16.9%. Patients with “at-risk MASH” (FibroScan-aspartate aminotransferase > 0.67) were 12.0%. A 2-tier screening for advanced liver fibrosis by FIB-4 and VCTE would have led to 70 patients (8.8%) referred to liver clinics with a false-negative rate of 9.6% (n = 77; patients with FIB-4 < 1.3 and LSM ≥ 8.0 kPa). At multivariate analysis, overweight/obesity (odds ratio = 3.13, 95% confidence interval 1.23–7.97) and elevated alanine aminotransferase (odds ratio = 1.91, 95% confidence interval 1.17–3.10) were independently associated with LSM ≥ 8.0 kPa in patients with FIB-4 < 1.3.DISCUSSION:In diabetes clinics, the 2-tier screening using FIB-4 and VCTE is effective for the identification of patients with T2DM to be referred to hepatologists. VCTE referral may be considered for patients with overweight/obesity and elevated alanine aminotransferase classified as at low risk of advanced liver fibrosis by FIB-4.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk for metabolic dysfunction-associated steatotic liver disease (MASLD), advanced liver fibrosis, and metabolic dysfunction-associated steatohepatitis (MASH). We evaluated the prevalence and severity of MASLD among patients with T2DM at their first referral to diabetes clinics, and assessed the effectiveness of the 2-tier screening approach by Fibrosis-4 (FIB-4) and vibration-controlled transient elastography (VCTE).BACKGROUND AIMSPatients with type 2 diabetes mellitus (T2DM) are at increased risk for metabolic dysfunction-associated steatotic liver disease (MASLD), advanced liver fibrosis, and metabolic dysfunction-associated steatohepatitis (MASH). We evaluated the prevalence and severity of MASLD among patients with T2DM at their first referral to diabetes clinics, and assessed the effectiveness of the 2-tier screening approach by Fibrosis-4 (FIB-4) and vibration-controlled transient elastography (VCTE).Consecutive patients with T2DM from six different diabetes clinics were prospectively enrolled. Liver stiffness measurement (LSM) was assessed by VCTE, while liver steatosis by controlled attenuation parameter (CAP) (Fibroscan, Echosens, France). \"At risk MASH\" was assessed by FibroScan-AST (FAST) score.METHODSConsecutive patients with T2DM from six different diabetes clinics were prospectively enrolled. Liver stiffness measurement (LSM) was assessed by VCTE, while liver steatosis by controlled attenuation parameter (CAP) (Fibroscan, Echosens, France). \"At risk MASH\" was assessed by FibroScan-AST (FAST) score.800 patients (median age: 59, 53-65 years; males: 485, 60.6%) met the inclusion criteria. Prevalence of liver steatosis (CAP ≥ 248 db/m) was 73.6%. The proportion of patients at medium/high risk of advanced liver fibrosis (LSM ≥ 8.0 kPa) was 16.9%. Patients with \"at risk MASH\" (FAST > 0.67) were 12.0%.A 2-tier screening for advanced liver fibrosis by FIB-4 and VCTE would have led to 70 (8.8%) patients referred to liver clinics with a false-negative rate of 9.6% (n = 77; patients with FIB-4 < 1.3 and LSM ≥ 8.0 kPa). At multivariate analysis, overweight/obesity (OR = 3.13, 95%CI 1.23-7.97) and elevated ALT (OR = 1.91, 95%CI 1.17-3.10) were independently associated with LSM ≥ 8.0 kPa in patients with FIB-4 < 1.3.RESULTS800 patients (median age: 59, 53-65 years; males: 485, 60.6%) met the inclusion criteria. Prevalence of liver steatosis (CAP ≥ 248 db/m) was 73.6%. The proportion of patients at medium/high risk of advanced liver fibrosis (LSM ≥ 8.0 kPa) was 16.9%. Patients with \"at risk MASH\" (FAST > 0.67) were 12.0%.A 2-tier screening for advanced liver fibrosis by FIB-4 and VCTE would have led to 70 (8.8%) patients referred to liver clinics with a false-negative rate of 9.6% (n = 77; patients with FIB-4 < 1.3 and LSM ≥ 8.0 kPa). At multivariate analysis, overweight/obesity (OR = 3.13, 95%CI 1.23-7.97) and elevated ALT (OR = 1.91, 95%CI 1.17-3.10) were independently associated with LSM ≥ 8.0 kPa in patients with FIB-4 < 1.3.In diabetes clinics, the 2-tier screening using FIB-4 and VCTE is effective for the identification of T2DM patients to be referred to hepatologists. VCTE referral may be considered for patients with overweight/obesity and elevated ALT classified as at low risk of advanced liver fibrosis by FIB-4.CONCLUSIONSIn diabetes clinics, the 2-tier screening using FIB-4 and VCTE is effective for the identification of T2DM patients to be referred to hepatologists. VCTE referral may be considered for patients with overweight/obesity and elevated ALT classified as at low risk of advanced liver fibrosis by FIB-4.

Metabolic dysfunction‐associated steatotic liver disease (MASLD), with its steadily increasing prevalence, represents now a major problem in public health. A proper referral could benefit from tools allowing more precise risk stratification. To this end, in recent decades, several genetic variants that may help predict and refine the risk of development and progression of MASLD have been investigated. In this review, we aim to discuss the role genetics in MASLD plays in everyday clinical practice. We performed a comprehensive literature search of PubMed for relevant publications. Available evidence highlights the emergence of genetic‐based noninvasive algorithms for diagnosing fatty liver, metabolic dysfunction‐associated steatohepatitis, fibrosis progression and occurrence of liver‐related outcomes including hepatocellular carcinoma. Nevertheless, their accuracy is not optimal and application in everyday clinical practice remains challenging. Furthermore, susceptible genetic markers have recently become subjects of great scientific interest as therapeutic targets in precision medicine. In conclusion, decisional algorithms based on genetic testing in MASLD to facilitate the clinician decisions on management and treatment are under growing investigation and could benefit from artificial intelligence methodology.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, characterized by late diagnosis, rapid progression, and limited therapeutic options. Despite advancements, only 20% of patients are eligible for surgical resection at diagnosis, the sole curative treatment. Multidisciplinary evaluation is critical to optimize care, stratifying patients based on resectability into resectable, borderline resectable, locally advanced, and metastatic stages. Preoperative imaging, such as computed tomography (CT) and endoscopic ultrasound (EUS), remains central for staging, for vascular assessment, and tissue acquisition. Endoscopic and systemic approaches are pivotal for addressing complications like biliary obstruction and improving outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) has been considered for years the gold standard for biliary drainage, although EUS-guided drainage is increasingly utilized due to its efficacy in both resectable and unresectable disease. Systemic therapies play a key role in neoadjuvant, adjuvant, and palliative settings, with ongoing trials exploring their impact on survival and resectability chance. This review highlights the evolving multidisciplinary approaches tailored to the disease stage, focusing on biliary drainage techniques, systemic therapies, and their integration into comprehensive care pathways for PDAC. The continuous refinement of these strategies offers incremental survival benefits and underscores the importance of personalized, multidisciplinary management.