In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma ...(HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonography with or without alpha-fetoprotein (AFP) in patients with advanced fibrosis. Furthermore, the use of non-invasive tools could represent a strategy to implement surveillance performance. In this review, we analyzed the main risk factors of NAFLD-related HCC, the validated screening methods and the future perspectives.
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.
Electrocautery-tip lumen-apposing metal stents (EC-LAMSs) have extended the indications of therapeutic EUS. We aimed to retrospectively evaluate safety and technical and clinical success of a newly ...developed EC-LAMS, the Hot-Spaxus (Taewoong Medical Co, Gimpo, Korea), for various EUS-guided procedures.
We included and retrospectively analyzed consecutive patients at 8 tertiary care referral centers who had undergone EUS interventional procedures using the Hot-Spaxus between October 2018 and February 2021.
Of 58 included patients (male-to-female, 36:22; mean age, 63.5 ± 14.9 years), 29 had undergone pancreatic fluid collection drainage (50%), 22 (37.9%) biliary drainage for malignant distal obstruction, 3 (5.1%) gallbladder drainage for acute cholecystitis, 3 gastroenteroanastomoses, and 1 (1.7%) pelvic collection drainage. Technical success was achieved in 54 of 58 patients (93.1%) and clinical success in all 58. Adverse events occurred in 6 patients (11.1%): 2 early (3.7%), 1 late (1.8%), and 3 long term (5.6%). The outcomes were similar to those observed in a control group of patients treated with the Hot-Axios (Boston Scientific, Marlborough, Mass, USA), the other available EC-LAMS.
Our study showed that the novel EC-LAMS has high technical and clinical success rates for various interventional EUS indications. Future multicenter prospective studies will better clarify the role of this new EC-LAMS for different indications.
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The non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease as well as the first cause of liver transplantation. NAFLD is commonly associated with ...metabolic syndrome (MetS), and this is the most important reason why it is extremely difficult to treat this disease bearing in mind the enormous amount of interrelationships between the liver and other systems in maintaining the metabolic health. The treatment of NAFLD is a key point to prevent NASH progression to advanced fibrosis, to prevent cirrhosis and to prevent the development of its hepatic complications (such as liver decompensation and HCC) and even extrahepatic one. A part of the well-known healthy effect of diet and physical exercise in this setting it is important to design the correct pharmaceutical strategy in order to antagonize the progression of the disease. In this regard, the current review has the scope to give a panoramic view on the possible pharmacological treatment strategy in NAFLD patients.
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.
Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver‐related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic ...comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis‐4 (FIB‐4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation) was used as the outcome. LREs were experienced by 58 patients, only one of whom was in the cohort of patients with a FIB‐4 score < 1.3. Multivariate Cox regression analysis of 229 patients with a FIB‐4 score ≥ 1.3 highlighted clinical variables independently associated with the development of LREs, including older age, low platelet count, low albumin, low high‐density lipoprotein cholesterol, certain genetic factors, and interactions between genetic factors and sex or diabetes. The area under the curve (AUC) for the model was 0.87 at 1, 3, and 5 years. Our novel Genetic and Metabolic Staging (GEMS) scoring system was derived from the Cox model linear predictor, ranked from 0 to 10, and categorized into five classes (0‐5, 5‐6, 6‐7, 7‐8, and 8‐10). The risk of LREs increased from 4% in patients in the best class (GEMS score 0‐5) to 91% in the worst (GEMS score 8‐10). GEMS score was associated with incident severe liver disease in the study population (hazard ratio, 1.56; 95% confidence interval, 1.48‐1.65; P < 0.001) as well as in the UK Biobank cohort where AUCs for prediction of severe liver disease at 1, 3, and 5 years were 0.70, 0.69, and 0.67, respectively. Conclusion: The novel GEMS scoring system has an adequate ability to predict the outcome of patients with NAFLD.
Abstract
Background and study aims
Chronic radiation proctitis (CRP) occurs in 5 % to 20 % of patients undergoing pelvic radiation therapy and frequently manifests with rectal bleeding. Endoscopic ...management of more severe and refractory cases can be challenging. Rectal band ligation (RBL) has been shown to be a feasible alternative to current available techniques, especially in extensive CRP. Our aim is to evaluate clinical and technical success of RBL.
Patients and methods
We enrolled all consecutive patients treated with RBL for severe or recurrent hemorrhagic CRP. Success was defined as endoscopic evidence of complete rectal healing and/or cessation of bleeding not requiring further treatment or blood transfusion.
Results
We enrolled 10 patients (7 males, mean age 75.6 years). Median length of the CRP from the anal verge was 4.5 cm and mean surface area involved was 89 %. Eight patients (80 %) were naïve to endoscopic treatment, while two had undergone argon plasma coagulation (APC). Median follow-up was 136.5 days. Success was achieved in 100 % of patients after a mean number of 1.8 RBL sessions. A mean number of 4.7 bands were released in the first session while a mean of 3.1 and 2 bands were placed in the second and third sessions, respectively. As for adverse events, only one patient reported mild tenesmus and pelvic pain after the procedure.
Conclusions
RBL is a safe and effective therapeutic modality for the treatment of hemorrhagic CRP. It could be considered a valid first-line option in case of extensive rectal involvement as well as a viable rescue treatment after failed APC.
Video 1
EUS-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.
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.
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.
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.
Patients with NAFLD carrying PNPLA3 rs738409 G>C variant are at higher risk of liver-related events and death.
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