Hyperferritinemia in Nonalcoholic Fatty Liver Disease: Iron Accumulation or Inflammation?
Semin Liver Dis DOI: 10.1055/s-0039-1693114Hyperferritinemia, observed in inflammation, iron overload as well as in combination of both, is found in ∼30% of nonalcoholic fatty liver disease (NAFLD) patients. The authors summarized the evidence regarding the potential cause of hyperferritinemia in NAFLD, as this may affect the indicated therapy. A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, and the Cochrane library. In the majority of NAFLD patients, hyperferritinemia is due to inflammation without hepatic iron overload. In a smaller group, a dysmetabolic iron overload syndrome (DIOS) is found, ...
Source: Seminars in Liver Disease - July 21, 2019 Category: Gastroenterology Authors: Moris, Wenke Verhaegh, Pauline Jonkers, Daisy Deursen, Cees van Koek, Ger Tags: Review Article Source Type: research
Noncoding RNA in Liver Regeneration —From Molecular Mechanisms to Clinical Implications
Semin Liver Dis DOI: 10.1055/s-0039-1693513The unique ability of the adult liver to regenerate after injury is the basis for efficient surgical resection and liver transplantation and provides solutions for the treatment of liver cancer and acute liver failure. Current success in surgical treatments could be enhanced by directed regulation of liver regeneration. A number of small molecules and growth factors have been tested in mice models to improve liver regeneration. Noncoding ribonucleic acids (ncRNA) are less studied regulators of various cellular processes. Here, the authors carefully review ncRNA involved in liver r...
Source: Seminars in Liver Disease - July 18, 2019 Category: Gastroenterology Authors: Sergeeva, Olga Sviridov, Evgeny Zatsepin, Timofei Tags: Review Article Source Type: research
Effects of Antibiotic Therapy in Primary Sclerosing Cholangitis with and without Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Semin Liver Dis DOI: 10.1055/s-0039-1688501The authors conducted a systematic review and meta-analysis to assess the effect of antibiotic therapy in primary sclerosing cholangitis (PSC). Effect of antibiotic therapy on Mayo PSC Risk Score (MRS), serum alkaline phosphatase (ALP), total serum bilirubin (TSB), and adverse events (AEs) rates were calculated and expressed as standardized difference of means or proportions. Five studies including 124 PSC patients who received antibiotics were included. Overall, antibiotic treatment was associated with a statistically significant reduction in ALP, MRS, and TSB by 33.2, 36.1, and ...
Source: Seminars in Liver Disease - July 16, 2019 Category: Gastroenterology Authors: Shah, Ayesha Crawford, Darrel Burger, Daniel Martin, Neal Walker, Marjorie Talley, Nicholas J. Tallis, Caroline Jones, Michael Stuart, Katherine Keely, Simon Lewindon, Peter Macdonald, Graeme A. Morrison, Mark Holtmann, Gerald J. Tags: Review Article Source Type: research
Vascular Targets for the Treatment of Portal Hypertension
Semin Liver Dis DOI: 10.1055/s-0039-1693115Portal hypertension is the main driver for severe complications in patients with liver cirrhosis. With improved understanding of molecular pathways that promote hepatic vascular remodeling, vasoconstriction, and sinusoidal capillarization potential vascular targets for the treatment of portal hypertension have been identified. Inhibition of vascular endothelial and platelet-derived growth factors–driven angiogenesis has been shown to reduce portal pressure and decrease hepatic inflammation. Angiopoietin/Tie signaling represents additional promising vascular targets in liver dise...
Source: Seminars in Liver Disease - July 16, 2019 Category: Gastroenterology Authors: Brusilovskaya, Ksenia K önigshofer, Philipp Schwabl, Philipp Reiberger, Thomas Tags: Review Article Source Type: research
Portal Hypertensive Biliopathy in Adult Patients: Findings and Interventional Radiologic Treatment —A Single-Center Experience
Semin Liver Dis DOI: 10.1055/s-0039-1693514The aim of this study was to evaluate the morphologic appearance, the clinical scenario, and the outcomes of patients with portal hypertensive biliopathy (PHB), particularly in the symptomatic subgroup treated with interventional radiology (IR) procedures. The outcome of 20 patients with PHB were retrospectively reviewed over a 5-year period. In all cases, the extrahepatic portal vein occlusion (EHPVO) and the compensatory cavernomatosis was the cause of PHB. Eight out of 20 patients had severe symptoms (jaundice and bleeding). Five out of these eight patients were successfully tr...
Source: Seminars in Liver Disease - July 3, 2019 Category: Gastroenterology Authors: Cappelli, Alberta Modestino, Francesco Mosconi, Cristina De Benedittis, Caterina Bruno, Antonio Papadopoulos, Dimitris Vitale, Giovanni Cucchetti, Alessandro Berardi, Sonia Morelli, Maria Cristina Golfieri, Rita Tags: Review Article Source Type: research
Hepatitis B Virus –Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms
Semin Liver Dis DOI: 10.1055/s-0039-1685518Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide. While current therapeutic approaches can efficiently control viral infection, efficient curative antivirals are absent. The understanding of virus–hepatocyte interactions and sensing of viral infection is an important prerequisite for the development of novel antiviral therapies for cure. Hepatocyte intrinsic innate immunity provides a rapid first line of defense to combat viral infection through the upregulation of antiviral and inflammatory genes. However, the functional relevance...
Source: Seminars in Liver Disease - July 1, 2019 Category: Gastroenterology Authors: Thomas, Emmanuel Baumert, Thomas F. Tags: Review Article Source Type: research
Heterogeneity of Hepatocellular Carcinoma on Imaging
Semin Liver Dis DOI: 10.1055/s-0039-1693512Tumor heterogeneity in hepatocellular carcinomas (HCC) occurs at different levels. On conventional imaging modalities, the spectrum of tumor heterogeneity is evident in the dynamic enhancement pattern, where the characteristic wash-in and wash-out is present in only 60% of small HCCs. In larger HCCs, heterogeneity within the tumor, known as the mosaic pattern, can reflect the presence of different grades of HCC differentiation. The advent of functional imaging techniques has not improved the diagnostic sensitivity of imaging techniques for the diagnosis of HCC. However, the combin...
Source: Seminars in Liver Disease - July 1, 2019 Category: Gastroenterology Authors: Rimola, Jordi Tags: Review Article Source Type: research
Macrophages as a Cell-Based Therapy for Liver Disease
Semin Liver Dis DOI: 10.1055/s-0039-1688502Liver failure arising from acute and chronic liver disease is an unmet clinical need that urgently requires novel therapeutic options in addition to orthotopic liver transplantation. Cell therapies offer new strategies to recover liver function through the reconstitution of healthy parenchyma and resolution of tissue pathology. Macrophages are professional phagocytes that comprise a key part of the innate immune system providing an important defense mechanism against invading pathogens. Macrophages are an inherently diverse cell type with respect to ontogeny, tissue distribution, ...
Source: Seminars in Liver Disease - June 25, 2019 Category: Gastroenterology Authors: Starkey Lewis, Philip J. Moroni, Francesca Forbes, Stuart J. Tags: Review Article Source Type: research
A Critical Review of MELD as a Reliable Tool for Transplant Prioritization
Semin Liver Dis DOI: 10.1055/s-0039-1688750In a context of global organ shortage, the Model for End-Stage Liver Disease (MELD) score seems to be a fair prioritization tool, with a paradigm: “sickest first.” Since its introduction in the United States in 2002, it has been rapidly adopted by transplant centers and organ sharing agencies around the world. The MELD score showed its effectiveness with a 12% reduction in waiting list mortality in the United States. Its success is linked to its simplicity, the use of basic variables (serum creatinine, serum bilirubin, and international normalized ratio [INR]), and its ability...
Source: Seminars in Liver Disease - June 25, 2019 Category: Gastroenterology Authors: Sacleux, Sophie-Caroline Samuel, Didier Tags: Review Article Source Type: research
Competing Endogenous RNAs in Hepatocellular Carcinoma —The Pinnacle of Rivalry
Semin Liver Dis DOI: 10.1055/s-0039-1688442The role of noncoding transcripts in gene expression is nowadays acknowledged to keep various diseases at bay—despite being referred to as “junk” DNA several years ago. Believed to be at the heart of multiple regulatory pathways, microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) involved in posttranscriptional gene regulation. Recently, the discovery of ncRNAs that compete for shared miRNA pools has dimmed the light on the solo performance of miRNAs in genomic regulation. Indeed, several studies describe RNAs such as long noncoding RNAs, mRNAs, circular RNAs, pseudogenes,...
Source: Seminars in Liver Disease - June 25, 2019 Category: Gastroenterology Authors: Afify, Abdelrahman Yousry Ibrahim, Salma Abdulmaqsoud Aldamsisi, Mennah Hisham Zaghloul, Mai Saad El-Ekiaby, Nada Abdelaziz, Ahmed Ihab Tags: Review Article Source Type: research
Circulating Tumor DNA and Hepatocellular Carcinoma
Semin Liver Dis DOI: 10.1055/s-0039-1688503There is a clear and unmet need for biomarkers in hepatocellular carcinoma (HCC). Circulating cell free deoxyribonucleic acid (cfDNA) is a fragmented DNA subtype, found in the blood circulation. Circulating tumor DNA (ctDNA) is the fraction of total cfDNA, which originates from the primary tumor or metastases in patients with cancer. Earlier studies reported that quantitative measurement cfDNA has diagnostic and prognostic role for HCC. More recently, improvement in next-generation sequencing technology and better understanding of genetic or epigenetic alteration of HCC have allow...
Source: Seminars in Liver Disease - June 20, 2019 Category: Gastroenterology Authors: Yang, Ju Dong Liu, Minetta C. Kisiel, John B. Tags: Review Article Source Type: research
The Contribution of B Cells in Autoimmune Liver Diseases
Semin Liver Dis DOI: 10.1055/s-0039-1688751Autoreactive B cells can promote autoimmunity through antigen presentation to autoreactive T cells, production of autoantibodies, generation of cytokines promoting T cell activation and differentiation, and inhibition of regulatory T cells and B cells. Here, the authors highlight studies pertaining to B cell mechanisms associated with disease pathogenesis and outcomes in autoimmune hepatitis and the immune-mediated cholangiopathies (primary biliary cholangitis, primary sclerosing cholangitis, and biliary atresia). The vast majority of investigations focus on autoantibodies and fut...
Source: Seminars in Liver Disease - June 20, 2019 Category: Gastroenterology Authors: Taylor, Sarah A. Assis, David N. Mack, Cara L. Tags: Review Article Source Type: research
Contributions of Fibroblasts, Extracellular Matrix, Stiffness, and Mechanosensing to Hepatocarcinogenesis
Semin Liver Dis DOI: 10.1055/s-0039-1685539Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. A unique feature of liver cancer is its close association with liver fibrosis. About 90% of HCCs develop in advanced liver fibrosis or cirrhosis, suggesting an important role for the fibrotic microenvironment in driving HCC development. Here, the authors will discuss functional contributions of liver fibrosis to the development of HCC, focusing on mechanisms through which fibrosis may promote HCC development such as hepatic stellate cell-derived extracellular matrix, growth factors, and cytoki...
Source: Seminars in Liver Disease - June 20, 2019 Category: Gastroenterology Authors: Filliol, Aveline Schwabe, Robert F. Tags: Review Article Source Type: research
Novel Drivers of the Inflammatory Response in Liver Injury and Fibrosis
Semin Liver Dis DOI: 10.1055/s-0039-1685515Hepatocyte demise as well as signals released by stressed hepatocytes have been now recognized as important triggers of liver inflammation. While traditional concepts classically viewed hepatocyte cell death to occur by either a nonlytic, noninflammatory form (apoptosis), or lytic, proinflammatory nonregulated cell death (necrosis), recent studies have provided evidence for additional mechanisms that can contribute to both acute and chronic liver damage. Two novel forms of cell death, pyroptosis and necroptosis, are of particular importance as they are highly regulated and intrins...
Source: Seminars in Liver Disease - May 16, 2019 Category: Gastroenterology Authors: Wree, Alexander Holtmann, Theresa Maria Inzaugarat, Maria Eugenia Feldstein, Ariel E. Tags: Review Article Source Type: research
Treatment Options for Metastatic Gastrointestinal Stromal Tumors to the Liver: A Review
Semin Liver Dis DOI: 10.1055/s-0039-1685517Up to half of patients with a gastrointestinal stromal tumor (GIST) will present with metastatic disease, most commonly involving the liver. Prior to the introduction of tyrosine kinase inhibitors, treatment options were limited for patients with metastatic GIST to the liver resulting in dismal survival rates. However, with the advent of effective systemic chemotherapy and continued advancements in both surgical and local adjunctive therapy options, significant improvements in survival have been achieved. In this review, the authors characterize the evolution of the treatment appr...
Source: Seminars in Liver Disease - May 16, 2019 Category: Gastroenterology Authors: Lillemoe, Heather A. Brudvik, Kristoffer W. Vauthey, Jean-Nicolas Tags: Review Article Source Type: research
