Enhanced Artificial Intelligence Methods for Liver Steatosis Assessment Using Machine Learning and Color Image Processing: Liver Color Project.

Background: The use of livers with significant steatosis is associated with worse transplantation outcomes. Brain death donor liver acceptance is mostly based on subjective surgeon assessment of liver appearance, since steatotic livers acquire a yellowish tone. The aim of this study was to develop a rapid, robust, accurate, and cost-effective method to assess liver steatosis.

An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor-induced liver injury.

Background: There are few data on corticosteroids (CS)-sparing strategies for checkpoint inhibitor (ICI)-induced liver injury (ChILI).

Aim: We aimed to assess the performance of a 2-step algorithm for severe ChILI, based on ICI temporary discontinuation (step-1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step-2).

Methods: Prospective study that included all subjects with grade 3/4 ChILI.

Optimization of Statin-Loaded Delivery Nanoparticles for Treating Chronic Liver Diseases by Targeting Liver Sinusoidal Endothelial Cells.

In this study, we developed functionalized polymeric micelles (FPMs) loaded with simvastatin (FPM-Sim) as a drug delivery system to target liver sinusoidal endothelial cells (LSECs) for preserving liver function in chronic liver disease (CLD). Polymeric micelles (PMs) were functionalized by coupling peptide ligands of LSEC membrane receptors CD32b, CD36 and ITGB3. Functionalization was confirmed via spectroscopy and electron microscopy.

ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation, Regardless of HBV Genotype.

Background And Aims: Hepatitis B virus (HBV) biomarkers have been used for a better categorization of patients, even though the lack of simple algorithms and the impact of genotypes limit their application. Our aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers (ICs) in a single-point evaluation and to design a predictive model for their identification.

Methods: This retrospective-prospective study included 343 consecutive HBeAg-negative individuals.

Risk of infections in patients with NAFLD and Type 2 Diabetes under treatment with SGLT2 inhibitors and relationship with liver outcomes: A retrospective case-control study.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries, with its incidence growing parallel to the epidemics of obesity and type 2 diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are becoming a cornerstone in the management of cardiovascular health and some studies suggest the potential role in NAFLD. However, patients under treatment with SGLT2i are at risk of developing genitourinary fungal infections (GFIs).

Ultra Deep Sequencing of Circulating Cell-Free DNA as a Potential Tool for Hepatocellular Carcinoma Management.

Background: Cell-free DNA (cfDNA) concentrations have been described to be inversely correlated with prognosis in cancer. Mutations in HCC-associated driver genes in cfDNA have been reported, but their relation with patient's outcome has not been described. Our aim was to elucidate whether mutations found in cfDNA could be representative from those present in HCC tissue, providing the rationale to use the cfDNA to monitor HCC.

A Nine-Strain Bacterial Consortium Improves Portal Hypertension and Insulin Signaling and Delays NAFLD Progression In Vivo.

The gut microbiome has a recognized role in Non-alcoholic fatty liver disease (NAFLD) and associated comorbidities such as Type-2 diabetes and obesity. Stool transplantation has been shown to improve disease by restoring endothelial function and insulin signaling. However, more patient-friendly treatments are required.

Retreatment With Immune Checkpoint Inhibitors After a Severe Immune-Related Hepatitis: Results From a Prospective Multicenter Study.

Background & Aims: Liver injury related to immunotherapy is a relatively frequent immune-related adverse event that requires permanent discontinuation of immune checkpoint inhibitors (ICIs) in severe cases. We present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis.

Methods: We performed a prospective, multicenter, noninterventional study that included all consecutive patients with cancer and previous grade 3 or 4 immune-related hepatitis who were retreated with ICIs in 3 academic hospitals.

Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study.

Background: There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects.

Aim: To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.

Synergic effect of atorvastatin and ambrisentan on sinusoidal and hemodynamic alterations in a rat model of NASH.

In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model.

ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity.

ARMCX3 is encoded by a member of the Armcx gene family and is known to be involved in nervous system development and function. We found that ARMCX3 is markedly upregulated in mouse liver in response to high lipid availability, and that hepatic ARMCX3 is upregulated in patients with NAFLD and hepatocellular carcinoma (HCC). Mice were subjected to ARMCX3 invalidation (inducible ARMCX3 knockout) and then exposed to a high-fat diet and diethylnitrosamine-induced hepatocarcinogenesis.

Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC).

Clear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients.

Steatosis as main determinant of portal hypertension through a restriction of hepatic sinusoidal area in a dietary rat nash model.

Background & Aims: Portal hypertension (PH) can be present in pre-cirrhotic stages, even in absence of fibrosis in non-alcoholic steatohepatitis (NASH) patients. Liver endothelial dysfunction (ED) has been shown as responsible for this effect in short-term dietary animal models. We evaluated the persistence of PH and underlying mechanisms in a long-term rat model of NASH.

Secondary syphilis with liver involvement in a liver transplant recipient.

Syphilis is capable of compromising almost any organ; however, syphilitic hepatitis is a rare manifestation that has been described most often in HIV-infected patients. Herein, we present a 33-year-old male liver transplant recipient who presented with progressive liver dysfunction characterized by mild ALT elevation and rising cholestasis, malaise, skin rash, and alopecia. Skin biopsy was characteristic of secondary syphilis, confirmed by both skin and liver biopsy-positive immunohistochemical staining for Treponema pallidum.

Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype.

Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial-mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase (PPIase) activity of cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here we demonstrate that in cultured TECs, CypA silencing triggers loss of epithelial features and enhances transforming growth factor β (TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail.

Restoration of liver sinusoidal cell phenotypes by statins improves portal hypertension and histology in rats with NASH.

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disorder in developed countries, with the associated clinical complications driven by portal hypertension (PH). PH may precede fibrosis development, probably due to endothelial dysfunction at early stages of the disease. Our aim was to characterize liver sinusoidal endothelial cell (LSEC) dedifferentiation/capillarization and its contribution to PH in NASH, together with assessing statins capability to revert endothelial function improving early NASH stages.

Is the involvement of the hepatic artery lymph node a poor prognostic factor in pancreatic adenocarcinoma?

Introduction: The aim of this study is to analyze the impact of hepatic artery lymph node (HALN) involvement on the survival of patients undergoing pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA).

Methods: A single-center retrospective study analyzing patients who underwent PD for PA. Patients were included if, during PD, the HALN was submitted for pathologic evaluation.

Sclerosing Cholangitis Related to IgG4: Not Always a Curable Entity.

IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis.

Thrombotic thrombocytopenic purpura relapse induced by acute hepatitis E transmitted by cryosupernatant plasma and successfully controlled with ribavirin.

Background: Hepatitis E virus (HEV) can be transmitted by transfusion of any type of blood component, but there are few data on the potential risk of transmitting this virus and the associated complications. We provide evidence that HEV can be transmitted by cryosupernatant plasma, and that HEV infection can act as a trigger for thrombotic thrombocytopenic purpura (TTP).

Study Design And Methods: A patient with a history of TTP treated with plasmapheresis 2 months previously developed jaundice and a TTP exacerbation with purpura, thrombocytopenia, schistocytes, and undetectable ADAMTS-13 activity.

Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis.

Unlabelled: Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal microbiota (IM) have been scarcely studied. Our aim was to investigate the role of the IM in the mechanisms leading to PH in early NASH.

Restrictive allograft syndrome and idiopathic pleuroparenchymal fibroelastosis: do they really have the same histology?

Aims: Restrictive allograft syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation, with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis.

Clinical Implications of Focal Intimal Disruption in Patients With Type B Intramural Hematoma.

Background: Focal intimal disruption (FID) has been described in >20% of type B intramural hematomas (IMH), with unclear prognosis and management.

Objectives: This study aimed to evaluate the short- and long-term evolution of medically treated patients with type B IMH with and without FID.

Methods: There were 107 consecutive patients with acute type B IMH were included prospectively in a multicenter protocol of clinical and imaging follow-up.