Evolution of liver fibrosis in diabetic patients with NAFLD in a follow-up study: Hepatoprotective effects of sodium-glucose co-transporter-2 inhibitors.

Background And Aims: Patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are at high risk of hepatic fibrosis. To prospectively evaluate changes in fibrosis in diabetic patients with NAFLD, predisposing factors and sodium glucose cotransporter 2 inhibitors (SGLT2i) influence.

Methods: 237 T2DM outpatients (mean age 67 ± 9 years, 54% male) were enrolled and re-evaluated after 52 ± 10 months.

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by an enhanced activation of the immune system, which predispose the evolution to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Resident macrophages and leukocytes exert a key role in the pathogenesis of NAFLD. In particular, CD4+ effector T cells are activated during the early stages of liver inflammation and are followed by the increase of natural killer T cells and of CD8+ T cytotoxic lymphocytes which contribute to auto-aggressive tissue damage.

Genetics, Immunity and Nutrition Boost the Switching from NASH to HCC.

Nonalcoholic fatty liver disease (NAFLD) is the leading contributor to the global burden of chronic liver diseases. The phenotypic umbrella of NAFLD spans from simple and reversible steatosis to nonalcoholic steatohepatitis (NASH), which may worsen into cirrhosis and hepatocellular carcinoma (HCC). Notwithstanding, HCC may develop also in the absence of advanced fibrosis, causing a delayed time in diagnosis as a consequence of the lack of HCC screening in these patients.

Ceruloplasmin gene variants are associated with hyperferritinemia and increased liver iron in patients with NAFLD.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder resulting from genetic and environmental factors. Hyperferritinemia has been associated with increased hepatic iron stores and worse outcomes in patients with NAFLD. The aim of this study was to evaluate the prevalence of variants of iron-related genes and their association with hyperferritinemia, hepatic iron stores and liver disease severity in patients with NAFLD.

Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and expose patients to increased risk of hepatic and cardiovascular (CV) morbidity and mortality. Both environmental factors and genetic predisposition contribute to the risk. An inappropriate diet, rich in refined carbohydrates, especially fructose, and saturated fats, and poor in fibers, polyunsaturated fats, and vitamins is one of the main key factors, as well as the polymorphism of patatin-like phospholipase domain containing 3 (PNPLA3 gene) for NAFLD and the apolipoproteins and the peroxisome proliferator-activated receptor (PPAR) family for the cardiovascular damage.

Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP).

Background: Chronic hepatitis C (CHC) is associated with hepatic steatosis, related to both a direct viral action and metabolic features. Vice-versa data on hepatic steatosis after viral eradication by direct-acting antiviral agents (DAA) are undefined although the presence of metabolic alterations could strongly influence the occurrence of steatosis as in NAFLD. The controlled attenuation parameter (CAP) (FibroscanⓇ) allows the qualitative and quantitative evaluation of fatty liver.

NAFLD fibrosis score (NFS) can be used in outpatient services to identify chronic vascular complications besides advanced liver fibrosis in type 2 diabetes.

We demonstrate in 351 diabetic patients with steatosis that NAFLD fibrosis score (NFS), a rapid and affordable score to diagnose hepatic fibrosis, identifies patients at higher risk of advanced fibrosis and vascular diabetic complications (especially peripheral neuropathy), pointing NFS as a first-line vascular and hepatic screening in diabetic patients.

Neurotensin up-regulation is associated with advanced fibrosis and hepatocellular carcinoma in patients with MAFLD.

Background & Aims: Neurotensin (NTS), a 13-aminoacid peptide localized in central nervous system and gastrointestinal tract, is involved in lipid metabolism and promotes various cancers onset mainly by binding to neurotensin receptor 1 (NTSR1). Increased plasma levels of pro-NTS, the stable NTS precursor, have been associated with type 2 diabetes (T2D), cardiovascular diseases and metabolic associated fatty liver disease (MAFLD). We aimed to evaluate 1) the impact of NTS rs1800832 and NTSR1 rs6090453 genetic variants on liver damage in 1166 MAFLD European individuals, 2) the relation between NTS variant and circulating pro-NTS and 3) the hepatic NTS expression by RNAseq transcriptomic analysis in 125 bariatric patients.

Liver involvement in Gaucher disease: A practical review for the hepatologist and the gastroenterologist.

Gaucher disease (GD), a rare lysosomal storage disorder caused by deficient glucocerebrosidase activity and consequent accumulation of glycosphingolipids in the mononuclear phagocyte system, may progress to disabling and potentially life-threatening complications when left undiagnosed and untreated. Unfortunately, because of non-specific signs and symptoms and lack of awareness, patients with type 1 GD, the most common non-neuropathic variant, frequently experience diagnostic delays. Since splenomegaly and thrombocytopenia are the dominant clinical features in many GD patients leading to first medical contact, the hepatologist and the gastroenterologist need to be aware of this condition.

Dysmetabolic Hyperferritinemia and Dysmetabolic Iron Overload Syndrome (DIOS): Two Related Conditions or Different Entities?

Hyperferritinemia is observed in one-third of patients with non-alcoholic fatty liver disease (NAFLD) and Metabolic Syndrome (MetS). The condition characterized by increased body iron stores associated with components of MetS has been defined as Dysmetabolic Iron Overload Syndrome (DIOS). DIOS represents the most frequent iron overload condition, since it is observed in 15% of patients with MetS and in half of those with NAFLD and its clinical presentation overlaps almost completely with that of dysmetabolic hyperferritinemia (DH).

Combined use of Genetic Polymorphisms and Elastographic Techniques in NAFLD: Fact or Fiction?

Non-alcoholic fatty liver disease (NAFLD) includes liver diseases ranging from simple steatosis to progressive forms characterized by high rates of complications and mortality, namely fibrosis, cirrhosis and hepatocellular carcinoma. Identification of patients with simple steatosis who will evolve to a more severe liver disease would allow better management of risk factors. Liver biopsy is the gold standard for the staging of NAFLD, however given its invasiveness it is not widely applicable.

Impact of natural neuromedin-B receptor variants on iron metabolism.

Iron overload heritability remains partly unexplained. By performing whole exome sequencing in three patients with a clinical phenotype of hemochromatosis not accounted by known genetic risk factors, we identified in all patients rare variants predicted to alter activity of Neuromedin-B receptor (NMBR). Coding NMBR mutations were enriched in 129 patients with hereditary hemochromatosis or iron overload phenotype, as compared to ethnically matched controls, including 100 local healthy blood donors and 1000Genomes project participants (15.

Liver fibrosis by FibroScan independently of established cardiovascular risk parameters associates with macrovascular and microvascular complications in patients with type 2 diabetes.

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.

High prevalence of early atherosclerotic and cardiac damage in patients undergoing liver transplantation: Preliminary results.

Liver transplanted patients are at high risk of metabolic syndrome and its complications. We aimed to prospectively evaluate the early onset of cardiovascular alterations in patients submitted to the transplant waiting list. From January 2014 to January 2016, 54 out of 79 patients on the waiting list with decompensated cirrhosis or hepatocellular-carcinoma received the transplant, 50 were followed for 24 months, 2 died post-surgery and 2 were lost to follow-up.

Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis.

Background & Aims: Patients with chronic HCV infection besides hepatitis often present cardiovascular damage, the pathogenesis of which is not defined. In chronic liver diseases, including NAFLD and cirrhosis, a procoagulant imbalance, potentially responsible for atherosclerosis has been reported. We aimed at evaluating whether a procoagulant imbalance is present also in non-cirrhotic patients with HCV infection and whether the procoagulant imbalance correlates with cardiovascular damage.

Brain involvement in non-alcoholic fatty liver disease (NAFLD): A systematic review.

Non-alcoholic fatty liver disease (NAFLD) is associated with high cardiovascular morbidity and mortality which usually is considered to be related to cardiac involvement, while scarce attention is addressed to brain damage. Viceversa NAFLD is associated with asymptomatic brain lesions, alterations in cerebral perfusion and activity, cognitive impairment and brain aging and with increased risk and severity of both ischemic and haemorrhagic stroke. Besides known metabolic risk factors, NAFLD is characterized by a pro inflammatory state, which contributes to atherosclerosis and microglia activation, endothelial dysfunction, pro-coagulant state and platelets activation, which in turn promote both micro and macrovascular damage eventually responsible for clinical and subclinical cerebrovascular alterations.

gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients.

Dyslipidemia and altered iron metabolism are typical features of nonalcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 () gene variation has been associated with circulating lipids and liver damage during iron overload. The aim of this study was to examine the impact of the rs236918 variant on NAFLD-related traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS).

Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n = 181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000 G.

Prevalence and Risk Factors of Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Without Steatohepatitis.

Background & Aims: In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis.

Evaluation of three "beyond Baveno VI" criteria to safely spare endoscopies in compensated advanced chronic liver disease.

Background: Liver stiffness measurement (LSM) <20 kPa and platelet count >150,000/mm exclude varices needing treatment (VNT) in viral compensated advanced chronic liver disease (cACLD), saving-up to 20-25% endoscopies (Baveno VI criteria). Refinements of such criteria to further reduce endoscopies and an approach without LSM (Platelet 150/MELD 6) were later proposed.

Aims: To assess LSM 25/platelet 125, LSM 25/platelet 110 (Expanded-Baveno VI) and Platelet 150/MELD 6 accuracy versus Baveno VI criteria, and the impact of platelet count variability on criteria accuracy in all-etiologies cACLD.

miRNA Signature in NAFLD: A Turning Point for a Non-Invasive Diagnosis.

Nonalcoholic fatty liver disease (NAFLD) defines a wide pathological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may predispose to liver cirrhosis and hepatocellular carcinoma. It represents the leading cause of hepatic damage worldwide. Diagnosis of NASH still requires liver biopsy but due to the high prevalence of NAFLD, this procedure, which is invasive, is not practicable for mass screening.

FibroScan Identifies Patients With Nonalcoholic Fatty Liver Disease and Cardiovascular Damage.

Patients with nonalcoholic fatty liver disease (NAFLD), particularly in the presence of nonalcoholic steatohepatitis or fibrosis, are at high cardiac and cerebrovascular risk..