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Background The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. Methods This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. Results 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %–93.9 %] vs. 87.8 % [95 %CI 82.1 %–92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %–96.3 %] vs. 95.5 % [95 %CI 91.4 %–98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P Conclusions The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.

Video 1EUS-guided ileal-ascending colon anastomosis with water-filled technique for pallation of cecal colon cancer invading the ileo-cecal valve, after failed attempt to perform ileal stenting.

Intraparenchymal lung masses inaccessible through bronchoscopy or endobronchial ultrasound guidance pose a diagnostic challenge. Furthermore, some fragile or hypoxic patients may be poor candidates for transbronchial approaches. Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) offers a potential diagnostic approach to lung cancers adjacent to the esophagus. We aimed to evaluate the feasibility, accuracy, and safety of trans-esophageal EUS-FNA/FNB for tissue sampling of pulmonary nodules.We retrospectively analyzed data from patients with pulmonary lesions who underwent EUS-FNA/FNB between March 2015 and August 2021 at eight Italian endoscopic referral centers.A total of 47 patients (36 male; mean age 64.47 ± 9.05 years) were included (22 EUS-FNAs and 25 EUS-FNBs). Overall diagnostic accuracy rate was 88.9% (76.3-96.2%). The sensitivity and diagnostic accuracy were superior for EUS FNB sampling versus EUS-FNA (100% vs. 78.73%); P = 0.05, and (100% vs. 78.57%); P = 0.05, respectively. Additionally, sample adequacy was superior for EUS-FNB sampling versus EUS-FNA (100% vs. 78.5%); P = 0.05. Multivariate logistic regression analysis for diagnostic accuracy showed nodule size at the cutoff of 15 mm (OR 2.29, 1.04-5.5, P = 0.05) and use of FNB needle (OR 4.33, 1.05-6.31, P = 0.05) as significant predictors of higher diagnostic accuracy. There were no procedure-related adverse events.This study highlights the efficacy and safety of EUS-FNA/FNB as a minimally invasive procedure for diagnosing and staging peri-esophageal parenchymal lung lesions. The diagnostic yield of EUS-FNB was superior to EUS-FNA.

INTRODUCTION: In the last years the Hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. EVIDENCE ACQUISITION: We searched PubMed for articles published between January 1, 1995, through December 31, 2020, in English language. EVIDENCE SYNTHESIS: Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogenic effect of the virus. CONCLUSIONS: This review aimed to explore the evidence linking HCV infection with cardiovascular disease and to evaluate the impact of SVR after DAAs on cardiovascular complications.

BACKGROUND AND AIMS Non-alcoholic fatty liver (NAFLD) is a major cause of liver disease worldwide leading also to a higher risk of cardiovascular events. We aimed to evaluate the impact of fatty liver and fibrosis on cardiovascular risk in a general population. METHODS Five hundred and forty-two subjects included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study were recruited. Steatosis (controlled attenuation parameter > 288 dB/m) and severe fibrosis (low risk, liver stiffness measurement [LSM]

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver diseases worldwide, involving about 25% of people. NAFLD incorporates a large spectrum of pathological conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and its complications include hepatic decompensation and hepatocellular carcinoma (HCC). This progression occurs, over many years, in an asymptomatic way, until advanced fibrosis appears. Thus, the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis are key issues. To date, the histological assessment of fibrosis with liver biopsy is the gold standard, but obviously, invasiveness is the greater threshold. In addition, rare but potentially life-threatening complications, poor acceptability, sampling variability and cost maybe restrict its use. Furthermore, due to the epidemic of NAFLD worldwide and several limitations of liver biopsy evaluation, noninvasive assessment tools to detect fibrosis in NAFLD patients are needed.

Background & Aims Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients with NAFLD. Methods We followed 471 consecutive individuals at a hospital in Italy with a diagnosis of NAFLD based on histologic factors or a diagnosis of compensated NAFLD-related cirrhosis based on clinical factors for at least 6 months, from March 2004 through December 2018. We collected data on the occurrence of hepatic and extrahepatic outcomes, including decompensation and HCC, cardiovascular events and extrahepatic cancers, and overall and liver-related death. We detected the rs738409 G>C polymorphism in DNA from patient blood samples using the TaqMan assay. Results During a median follow-up time of 64.6 months (range 6.1–175 months) 26 cases of decompensation, 13 HCCs, and 16 deaths (12 liver-related) were recorded. All liver-related events, including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. The prevalence of PNPLA3 rs738409 GG, GT, and TT genotypes was 31.8%, 45.6%, and 22.6%, respectively. After adjusting for clinical, metabolic, and histologic risk factors, PNPLA3 C>G variant was associated with a higher risk of decompensation (hazard ratio [HR], 2.10; 95% CI, 1.03–4.29; P = .04), HCC (HR, 2.68; 95% CI, 1.01–7.26; P = .04), and liver-related death (HR, 3.64; 95% CI, 1.18–11.2; P = .02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis, we confirmed the independent association between the PNPLA3 variant and decompensation (HR, 2.00; 95% CI, 1.01–3.97; P = .04), HCC (HR, 2.66; 95% CI, 1.02–7.13; P = .04), and liver-related death (HR, 3.64, 95% CI, 1.18–11.2; P = .02). We found no association between PNPLA3 genotype and cardiovascular events, extrahepatic cancers, or overall mortality. Conclusions Patients with NAFLD carrying PNPLA3 rs738409 G>C variant are at higher risk of liver-related events and death.

Liver fibrosis is the main predictor of events in patients with nonalcoholic fatty liver disease (NAFLD),1 and its evolution is characterized by a nonlinear trend2,3 mostly affected by metabolic risk factors, severity of liver inflammation and steatosis, and weight loss.3 The rs738409 C>G common variant in PNPLA3 gene has been associated with severity of fibrosis and risk of liver-related events in NAFLD.4,5 Noninvasive tests as Fibrosis-4 (FIB-4) and liver stiffness measurement (LSM) are useful to rule-out advanced fibrosis and they could be reliable to predict fibrosis progression.2,6 We aimed to evaluate in patients with NAFLD whether PNPLA3 rs738409 C>G variant impacts on fibrosis progression, noninvasively assessed by FIB-4 and LSM.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world and the global epidemics of obesity and type 2 diabetes have led to a dramatic increase of its prevalence and incidence. Among NAFLD patients, those with nonalcoholic steatohepatitis (NASH) have a double risk of fibrosis progression, that is the main driver toward the evolution in cirrhosis and its complications, including hepatocellular carcinoma and hepatic decompensation. Furthermore, patients with NAFLD are also at risk for cardiovascular diseases and extrahepatic malignancies, that represent the first and the second cause of death, respectively. The availability of non-invasive scores to identify patients with NASH, avoiding to perform liver biopsy, still represents a relevant unmet medical need. Ideally, non-invasive biomarkers should be able to distinguish NASH patients among NALFD population, to assess the severity of liver fibrosis, to identify patients at risk of hepatic and extrahepatic complications and finally to predict the response to treatment. To date, liver biopsy remains the gold standard for the diagnosis and the stratification of the prognosis in NASH due to the lack of adequate non-invasive biomarkers in clinical practice. Several scores have been developed for the non-invasive assessment of fibrosis with promising results, although they are often limited by the high rate of false positive results and uncertainty areas. Further studies are needed to improve the diagnostic accuracy of non-invasive biomarkers or to develop new panels with the aim of predicting outcomes and response to treatments.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely associated, and liver fibrosis has been related to macrovascular complications. We examined whether liver fibrosis, diagnosed by FibroScan® , correlates with chronic vascular complications in a cohort of T2DM. METHODS: We recruited 394 outpatients with T2DM attending five Italian diabetes centres who underwent liver ultrasonography (US), FibroScan® and extensive evaluation of macrovascular and microvascular diabetic complications. RESULTS: Steatosis by US was present in 89%. Almost all patients (96%) were on hypoglycaemic drugs, 58% had at least one chronic vascular complication, 19% a macrovascular complication (prior myocardial infarction and/or ischaemic stroke) and 33% a microvascular one (26% chronic kidney disease [CKD]; 16% retinopathy; 6% neuropathy). In all, 171 (72%) patients had CAP ≥ 248dB/m (ie hepatic steatosis), whereas 83 (21%) patients had LSM ≥ 7.0/6.2 kPa (M/XL probes) (significant liver fibrosis). CAP was not associated with any macro/microvascular complications, whereas LSM ≥ 7.0/6.2 kPa was independently associated with prior cardiovascular disease (adjusted OR 3.3, 95%CI 1.2-8.8; P = .02) and presence of microvascular complications (adjusted OR 4.2, 95%CI 1.5-11.4; P = .005), mainly CKD (adjusted OR 3.6, 95%CI 1.3-10.1; P = .01) and retinopathy (adjusted OR 3.7, CI 95% 1.2-11.9; P = .02). Neither diabetes duration nor haemoglobin A1c differed according to CAP or LSM values. CONCLUSION: Significant fibrosis, detected by FibroScan® , is independently associated with increased prevalence of macrovascular and microvascular complications, thus opening a new scenario in the use of this tool for a comprehensive evaluation of hepatic and vascular complications in patients with T2DM.

Background and Aim: Non-alcoholic fatty liver disease(NAFLD) is an emergent cause of liver-related events(LRE). We have assessed the ability of a composite score based on clinical features, metabolic comorbidities and genetic background, to predict LRE. Methods: 546 consecutive patients with NAFLD were recruited and stratified according to FIB-4(low risk

Background: Patients with NAFLD are at higher risk of developing liver-related complications -liver decompensation(LD) and hepatocellular carcinoma (HCC), including death-. A single nucleotide polymorphism in PNPLA3 gene is associated with a higher prevalence of liver damage and HCC, but prospective date are not available. We aimed to assess whether the common rs738409 variant in PNPLA3 gene can predict the occurrence of liver-related events and death in a large cohort of NAFLD patients. Methods: We considered 471 consecutive Italian individuals with histological diagnosis of NAFLD or clinical diagnosis of compensated NAFLD-related cirrhosis, prospectively followed for at least 6 months. The occurrence of hepatic and extrahepatic outcomes was recorded (LD and HCC; cardiovascular events and extrahepatic cancers, overall and liver-related death). The rs738409 G>C polymorphisms was genotyped by TaqMan assay. Findings: During a median follow-up of 64.6 months 26 LD, 13 HCC and 16 deaths (12 liver-related) were recorded. All liver-related events including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. After adjusting for clinico-metabolic and histological risk factors PNPLA3 C>G variant was associated with a higher risk of LD(HR 2.10,95%C.I.1.03-4.29, p=0.04), HCC (HR 2.68,95%C.I.1.01-7.26, p=0.04) and liver-related death (HR 3.64, 5%C.I.1.18-11.2, p=0.02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis we confirmed the independent association of PNPLA3 variant with LD (HR 2.00,95%C.I.1.01-3.97, p=0.04), HCC (HR 2.66,95%C.I.1.02-7.13, p=0.04) and liver-related death (HR 3.64,95%C.I.1.18-11.2, p=0.02). No association was found between PNPLA3 genotype and cardiovascular events, extrahepatic cancers and overall mortality. Interpretations: Patients carrying PNPLA3 rs738409 G>C variant are at higher risk of developing liver-related events and death. Funding: None. Declaration of Interest: None. Ethical Approval: The study was carried out in accordance with the principles of the Helsinki Declaration, and with local and national laws. Approval was obtained from the AOUP “Giaccone” of Palermo.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.