Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19.

Background & Aims: The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19.

The Neglected Role of Bile Duct Epithelial Cells in NASH.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and affects 25% of the population in Western countries. NAFLD is the hepatic manifestation of the metabolic syndrome, linked to insulin resistance, which is the common pathogenetic mechanism. In approximately 40% of NAFLD patients, steatosis is associated with necro-inflammation and fibrosis, resulting in nonalcoholic steatohepatitis (NASH), a severe condition that may progress to cirrhosis and liver cancer.

NFkappaB, cytokines, TLR 3 and 7 expression in human end-stage HCV and alcoholic liver disease.

Background/aims: Conflicting observations exist concerning the role of nuclear factor kappa B (NFjB) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll-like receptors (TLRs) expressions in conjunction with NFkappaB activation in non-active end-stage human ALD compared with normal livers and hepatitis C virus (HCV) related end-stage disease.

Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression.

The transcription factor Oct4 is well defined as a key regulator of embryonic stem (ES) cell pluripotency. In recent years, the role of Oct4 has purportedly extended to the self renewal and maintenance of multipotency in adult stem cell (ASC) populations. This profile has arisen mainly from reports utilising reverse transcription-polymerase chain reaction (RT-PCR) based methodologies and has since come under scrutiny following the discovery that many developmental genes have multiple pseudogenes associated with them.

Deficient Stat3 DNA-binding is associated with high Pias3 expression and a positive anti-apoptotic balance in human end-stage alcoholic and hepatitis C cirrhosis.

Background/aims: In vitro and animal data suggest that alcohol and hepatitis C virus (HCV) proteins might interfere with Stat3 signaling, a potential regulator of liver cell apoptosis and proliferation.

Methods: We assessed Stat3 expression, activity and the apoptotic-proliferation balance in end-stage HCV and alcoholic liver disease (ALD) in man. Explanted livers of HCV and ALD patients were compared to normal and primary biliary cirrhosis (PBC) livers.

A novel cell-surface marker found on human embryonic hepatoblasts and a subpopulation of hepatic biliary epithelial cells.

The nature of the cells that contribute to the repopulation of the liver after hepatic necrosis or cirrhosis remains uncertain, in part because we lack specific markers to facilitate identification and prospective isolation of progenitor cells. The monoclonal antibody GCTM-5 reacts with a minority subpopulation of cells in spontaneously differentiating cultures of pluripotent human embryonal carcinoma or embryonic stem cells. The epitope recognized by GCTM-5 is found on a 50-kDa protein present on the surface of these cells.

The role of Notch receptor expression in bile duct development and disease.

Mutations in the Jagged1 gene, a ligand for the Notch signalling pathway, have been implicated in the pathogenesis of Alagille syndrome (AGS), resulting in bile duct paucity. Recently, a mouse model for AGS suggested that abnormalities of the Notch2 receptor, as well as of Jagged1, may be present. Expression patterns of Notch receptors have not been described in the developing human liver or in paediatric liver.

Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers.

The work of liver stem cell biologists, largely carried out in rodent models, has now started to manifest in human investigations and applications. We can now recognize complex regenerative processes in tissue specimens that had only been suspected for decades, but we also struggle to describe what we see in human tissues in a way that takes into account the findings from the animal investigations, using a language derived from species not, in fact, so much like our own. This international group of liver pathologists and hepatologists, most of whom are actively engaged in both clinical work and scientific research, seeks to arrive at a consensus on nomenclature for normal human livers and human reactive lesions that can facilitate more rapid advancement of our field.

Human liver-derived stem cells.

The search for human oval cells or bi-potential stem cells in the human liver is the subject of intensive investigation. Fetal hepatocytes (hepatoblasts) have some proliferative and bipotential capacity, but access to sufficient numbers of cells remains limiting. Candidate stem cells in the adult normal and diseased human liver have been identified using markers such as OV6, CD34, c-kit and NCAM.

Tissue engineering of human biliary epithelial cells on polyglycolic acid/polycaprolactone scaffolds maintains long-term phenotypic stability.

The biliary tree is the target of damage in a number of important liver diseases. Although human biliary epithelial cells (hBECs) can be maintained in vitro for up to 8 weeks, using double-collagen gels, which offer a substantial improvement compared with conventional tissue culture plastic, such gels are unstable and, being only semisolid, they do not lend themselves readily to routine analysis. In this study we have investigated the behavior of primary hBECs on polyglycolic acid (PGA) fiber mesh scaffolds.

Expression and DNA-binding activity of signal transducer and activator of transcription 3 in alcoholic cirrhosis compared to normal liver and primary biliary cirrhosis in humans.

In rats, activation of the cytokine-inducible transcription factor signal transducer and activator of transcription 3 (Stat3) is impaired in the liver after ethanol administration. The aim was to examine Stat3 expression, localization, and activity in alcoholic liver disease (ALD) in humans. Explanted livers of ALD patients were compared to normal and primary biliary cirrhosis livers.

Progenitor cells of the biliary epithelial cell lineage.

Stem-like cells have been identified in liver that are able to differentiate in vivo and in culture to biliary epithelial cells (BEC), hepatocytes and oval cells. The growth factors/cytokines and signal pathways required for the differentiation processes are beginning to be evaluated. There is increasing evidence to suggest that these stem-like cells may originate from both the bone marrow population or from a precursor remnant from liver embryogenesis, as they share many of the same markers (CD34, c-kit, CD45).

Altered Notch ligand expression in human liver disease: further evidence for a role of the Notch signaling pathway in hepatic neovascularization and biliary ductular defects.

The Jagged and Delta family of transmembrane proteins are ligands for Notch receptors, which control the proliferation and/or differentiation of many cell lineages. Expression and localization of these ligands in the adult human liver has not been fully elucidated, nor whether dysregulation of these proteins contributes to liver disease processes. We have examined expression of the five known Notch ligands in human liver.

A bioartificial liver--state of the art.

End-stage liver disease is treated by liver transplantation, but donor organ shortages remain a serious problem. This has prompted the design of bioartificial liver devices to "bridge" patients until they either recover or receive a liver transplant. In these devices, patient plasma is circulated extracorporeally through a bioreactor that houses liver cells (hepatocytes) sandwiched between artificial plates or capillaries.