Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease.

Objective: Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death.

Design: We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients.

Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia.

Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) are able to reduce liver injury and promote regeneration.

Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease.

Background & Aims: Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain.

Methods: The most common NSS (NFS, FIB-4, BARD, APRI) and the Hepamet fibrosis score (HFS) were assessed in 1,173 European patients with NAFLD from tertiary centres. Performance for fibrosis risk stratification and for the prediction of long-term hepatic/extrahepatic events, hepatocarcinoma (HCC) and overall mortality were evaluated in terms of AUC and Harrell's c-index.

Cooperative Role of Thrombopoietin and Vascular Endothelial Growth Factor-A in the Progression of Liver Cirrhosis to Hepatocellular Carcinoma.

Primary thrombopoietic mediator thrombopoietin (THPO) is mainly produced by the liver; it may act as a growth factor for hepatic progenitors. Principal angiogenesis inducer vascular endothelial growth factor-A (VEGF-A) is critical for the complex vascular network within the liver architecture. As a cross-regulatory loop between THPO and VEGF-A has been demonstrated in the hematopoietic system, the two growth factors were hypothesized to cooperatively contribute to the progression from liver cirrhosis (LC) to hepatocellular carcinoma (HCC).

Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: time for reappraisal of BMI-driven approach?

Objective: The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD.

Design: The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) View Article and Find Full Text PDF

Evaluation of Graft Fibrosis, Inflammation, and Donor-specific Antibodies at Protocol Liver Biopsies in Pediatric Liver Transplant Patients: A Single-center Experience.

Background: The impact of graft fibrosis and inflammation on the natural history of pediatric liver transplants is still debated. Our objectives were to evaluate the evolution of posttransplant fibrosis and inflammation over time at protocol liver biopsies (PLBs), risk factors for fibrosis, presence of donor-specific antibodies (DSAs), and/or their correlation with graft and recipient factors.

Methods: A single-center, retrospective (2000-2019) cross-sectional study on pediatric liver transplant recipients who had at least 1 PLB, followed by a longitudinal evaluation in those who had at least 2 PLBs, was conducted.

Presence of Serum Antinuclear Antibodies Does Not Impact Long-Term Outcomes in Nonalcoholic Fatty Liver Disease.

Introduction: We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD).

Methods: ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months.

Not only Alagille syndrome. Syndromic paucity of interlobular bile ducts secondary to HNF1β deficiency: a case report and literature review.

Background: paucity of interlobular bile ducts is an important observation at liver biopsy in the diagnostic work-up of neonatal cholestasis. To date, other than in the Alagille syndrome, syndromic paucity of interlobular bile ducts has been documented in four cholestatic neonates with HFN1β mutations. A syndromic phenotype, known as renal cysts and diabetes syndrome (RCAD), has been identified.

Long-Term Outcome of Veno-Occlusive Disease After Liver Transplant: A Retrospective Single-Center Experience.

Objectives: Veno-occlusive disease after liver transplant has been sporadically reported, and significant uncertainty exists concerning the best treatment and the long-term outcomes. Here, we reviewed our experience to evaluate clinical presentation, treatment, and the long-term outcomes of these patients.

Materials And Methods: Between 2000 and 2015, 2165 patients underwent liver transplant at our center.

Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

Background: The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV).

Successful Sequential Liver and Hematopoietic Stem Cell Transplantation in a Child With CD40 Ligand Deficiency and Cryptosporidium-Induced Liver Cirrhosis.

Background: Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency.

Transient elastography for non-invasive evaluation of post-transplant liver graft fibrosis in children.

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage.

Late-Onset Hepatic Veno-Occlusive Disease after Allografting: Report of Two Cases with Atypical Clinical Features Successfully Treated with Defibrotide.

Hepatic Veno-Occlusive Disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT who developed late onset VOD with atypical clinical features. The two patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor.

Hypoxia-inducible factor 2α drives nonalcoholic fatty liver progression by triggering hepatocyte release of histidine-rich glycoprotein.

Unlabelled: Mechanisms underlying progression of nonalcoholic fatty liver disease (NAFLD) are still incompletely characterized. Hypoxia and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of chronic liver diseases, but the actual role of HIF-2α in the evolution of NAFLD has never been investigated in detail. In this study, we show that HIF-2α is selectively overexpressed in the cytosol and the nuclei of hepatocytes in a very high percentage (>90%) of liver biopsies from a cohort of NAFLD patients at different stages of the disease evolution.

SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells.

SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-β1, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis.

The macrophage activation marker sCD163 is associated with morphological disease stages in patients with non-alcoholic fatty liver disease.

Background & Aims: Macrophage activation plays a key pathogenic role in experimental non-alcoholic fatty liver disease (NAFLD) and contributes to the progression of steatohepatitis (NASH) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s)CD163, a specific macrophage activation marker, hypothesizing that sCD163 would be associated with the patients' morphological disease grade. Furthermore, we investigated an association between sCD163 and the apoptosis marker cytokeratin-18 (CK-18) to explore a link between macrophage activation and apoptosis.

Prevalence and prognostic value of hepatic histological alterations in patients with Crohn's disease.

Unlabelled: Variable degrees of liver histological changes in patients with Crohn's disease (CD) have been reported.

Objective: To evaluate the liver histological alterations and their prognostic significance in patients affected by CD without abnormalities of liver biochemical parameters and ultrasound features.

Material And Methods: A prospective, single-blind study, including 35 consecutive patients with CD that underwent bowel resection with a contemporary performance of liver biopsy from 1992 to 2003.

Liver resection for hepatocellular carcinoma in patients with metabolic syndrome: A multicenter matched analysis with HCV-related HCC.

Background & Aims: The incidence of metabolic syndrome-related hepatocellular carcinoma (MS-HCC) is increasing worldwide. High resection risks are anticipated because of underlying steatohepatitis, but long-term results are unknown. To clarify the outcomes following liver resection in patients with MS-HCC and to compare the outcomes of MS-HCC to HCV-related HCC (HCV-HCC).

Hypoxia up-regulates SERPINB3 through HIF-2α in human liver cancer cells.

SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial-to-mesenchymal transition (EMT) and increased invasiveness in liver cancer cells. This study has investigated whether SERPINB3 expression is regulated by hypoxia-related mechanisms in liver cancer cells.

The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma.

Objective: The extracellular signal-regulated kinase 5 (ERK5 or BMK1) is involved in tumour development. The ERK5 gene may be amplified in hepatocellular carcinoma (HCC), but its biological role has not been clarified. In this study, we explored the role of ERK5 expression and activity in HCC in vitro and in vivo.

Multiparametric Gd-EOB-DTPA magnetic resonance in diagnosis of HCC: dynamic study, hepatobiliary phase, and diffusion-weighted imaging compared to histology after orthotopic liver transplantation.

Purpose: To evaluate Gd-EOB-DTPA-enhanced magnetic resonance (MR) performance during dynamic (DYN) phases, hepatobiliary (HB) phase and diffusion-weighted imaging (DWI) compared with pathological findings in patients undergoing orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with different conditions, such as stage of chronic liver disease, histological grading, nodule size, and occurrence of previous treatments.

Methods: Retrospective analysis of 64 nodules reported as HCC at pathological analysis on 28 explanted livers, examined about 3 months before OLT using a 1.5 T device and 16 channels array after intravenous GD-EOB-DTPA injection.

Liver transplantation for "mass-forming" sclerosing cholangitis after laparoscopic cholecystectomy.

Introduction: Chronic biliary obstruction consequence of a bile duct injury may require liver transplantation (LT) in case of secondary biliary cirrhosis, intractable pruritus or reiterate episodes of cholangitis. "Mass-forming" sclerosing cholangitis leading to secondary portal vein thrombosis and pre-sinusoidal portal hypertension has not been reported so far.

Presentation Of Case: We present the case of a patient who underwent laparoscopic cholecystectomy for Mirizzi syndrome.