Infection Control Practices and Outcomes of Endoscopy Units in the Lombardy Region of Italy: A Survey From the Italian Society of Digestive Endoscopy During COVID-19 Spread.

GOALS: The present survey from the Italian Society of Digestive Endoscopy (SIED-Società Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. BACKGROUND: Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. METHODS: A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. RESULTS: In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. CONCLUSIONS: Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients With Nonalcoholic Fatty Liver Disease.

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.

Impact of Obesity and Alanine Aminotransferase Levels on the Diagnostic Accuracy for Advanced Liver Fibrosis of Noninvasive Tools in Patients With Nonalcoholic Fatty Liver Disease.

INTRODUCTION: Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels. METHODS: We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured. RESULTS: LSM was better than both FIB-4 and NFS for staging F3-F4 fibrosis area under the receiver operating characteristic curve test (AUC) 0.863, 0.777, and 0.765, respectively; P < 0.001 for both), showing higher accuracy and higher negative predictive value (NPV), but lower positive predictive value (PPV). LSM worked less well in high ALT (>100 IU) (AUC 0.811 vs 0.877, P = 0.04; PPV 57.5% vs 62.4%; NPV 90.7% vs 94%) or obese patients (AUC 0.786 vs 0.902, P < 0.001; PPV 58.7% vs 64.8%; NPV 88.3% vs 95.2%), the latter not being affected by the M or XL probe. Consistently, LSM worked better in terms of AUC and accuracy compared with both FIB-4 and NFS only in nonobese or high ALT patients, even with always keeping a slightly lower PPV. A serial combination of FIB-4 or NFS with LSM as the second test in patients in the gray area of the first test retained-in most scenarios-similar PPV and NPV compared with LSM alone. These strategies also increased the diagnostic accuracy of about 20% in all groups of patients, even if with a lower overall accuracy in obese patients (71.3% and 67.1% for FIB-4 and NFS as the first test, respectively) compared to nonobese patients (81.9% and 82.4% for FIB-4 and NFS as the first test, respectively). CONCLUSIONS: All tested noninvasive tools have overall better NPV than PPV. LSM has a better diagnostic accuracy for advanced fibrosis than both FIB-4 and NFS only in nonobese and/or low ALT patients. Serial combination strategies are better than a single tool strategy, regardless of obesity and ALT levels, although the accuracy is lower in obese patients.

Endoscopic management of gastric outlet obstruction disease.

Gastric outlet obstruction (GOO) is a clinical syndrome characterized by a variety of symptoms. It may be caused by motor disorders and by benign or malignant mechanical disease. Endoscopic management of benign disease is mainly based on balloon dilation, augmented by the use of covered self-expanding metal stents (SEMS) in refractory disease. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is increasingly used as an alternative method, although more studies with longer follow up are needed before it can be considered as a recommended therapy. Surgery remains the last resort. Endoscopic management of malignant GOO is based on SEMS placement as an alternative to palliative surgery, because it is a cost-effective method. The use of a covered or uncovered stent depends on patient-related variables, which include the stricture site, concomitant involvement of the bile duct, the patient's prognosis, probably the tumor type, and the use of chemotherapy. EUS-GE is a promising technique but needs more studies with longer follow up before any firm conclusions can be drawn.

Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?

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.

Italian clinical practice guidelines on cholangiocarcinoma Part I: classification, diagnosis and staging

Cholangiocarcinoma (CCA) is the second most common primary liver cancer, characterized by a poor prognosis and resistance to chemotherapeutics. The progressive increase in CCA incidence and mortality registered worldwide in the last two decades and the need to clarify various aspects of clinical management have prompted the Italian Association for the Study of the Liver (AISF) to commission the drafting of dedicated guidelines in collaboration with a group of Italian scientific societies. These guidelines have been formulated in accordance with the Italian National Institute of Health indications and developed by following the GRADE method and related advancements.