The Matrisome, Inflammation, and Liver Disease
Semin Liver Dis DOI: 10.1055/s-0039-3402516Chronic fatty liver disease is common worldwide. This disease is a spectrum of disease states, ranging from simple steatosis (fat accumulation) to inflammation, and eventually to fibrosis and cirrhosis if untreated. The fibrotic stage of chronic liver disease is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins (collagens) that ultimately impairs the function of the organ. The role of the ECM in early stages of chronic liver disease is less well-understood, but recent research has demonstrated that several changes in the hepatic ECM in prefibrot...
Source: Seminars in Liver Disease - January 7, 2020 Category: Gastroenterology Authors: Dolin, Christine E. Arteel, Gavin E. Tags: Review Article Source Type: research

Aging and the Biological Response to Liver Injury
Semin Liver Dis DOI: 10.1055/s-0039-3402033Interest in understanding the aging process has recently risen in the scientific community. Aging, commonly defined as the functional decline in the function of organs and tissues, is indeed the major risk factor for the development of many chronic diseases, such as cardiovascular diseases, pathologies of nervous system, or cancer. To date, the influence of aging in the pathophysiology of liver and biliary diseases is not fully understood. Although liver cells have a high regenerative capacity, hepatocytes and cholangiocytes undergo extensive molecular changes in response to aging...
Source: Seminars in Liver Disease - December 30, 2019 Category: Gastroenterology Authors: Pinto, Claudio Ninfole, Elisabetta Gaggiano, Laura Benedetti, Antonio Marzioni, Marco Maroni, Luca Tags: Review Article Source Type: research

A Review on the Update of Combined Hepatocellular Cholangiocarcinoma
Semin Liver Dis DOI: 10.1055/s-0039-3402515Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation. This unique neoplasm is gaining increasing recognition due to the intriguing pathology, tumor biology, and clinical behavior. It also poses challenges in diagnosis, treatment, and research, largely because of its histological and phenotypic diversity that lead to confusion in terminology and classification. There have been efforts attempting to unify the terminology of this neoplasm recently. Advances in investigation in ...
Source: Seminars in Liver Disease - December 30, 2019 Category: Gastroenterology Authors: Komuta, Mina Yeh, Matthew M. Tags: Review Article Source Type: research

NS5A-P32 Deletion in Hepatitis C Genotype 1b Infection is the Most Refractory Treatment-Mediated Amino Acid Change Exhibiting Resistance to all NS5A Inhibitors
Semin Liver Dis DOI: 10.1055/s-0039-3402001NS5A-P32 deletion (P32del) is a resistance-associated amino acid change that has recently gained popularity in direct-acting antiviral treatment for chronic hepatitis C. Although not yet detected in naive patients, it appears in 5 to 10% of hepatitis C genotype 1b patients who fail to respond to daclatasvir/asunaprevir and sofosbuvir/ledipasvir treatments. In contrast to signature resistance-associated substitutions, such as substitutions at the NS5A-L31 and NS5A-Y93 positions, it shows complete resistance to all NS5A inhibitors in replicon and cell culture. Studies of humanized l...
Source: Seminars in Liver Disease - December 13, 2019 Category: Gastroenterology Authors: Hikita, Hayato Takehara, Tetsuo Tags: Review Article Source Type: research

Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma
Semin Liver Dis DOI: 10.1055/s-0039-3399534Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed ...
Source: Seminars in Liver Disease - December 6, 2019 Category: Gastroenterology Authors: Lim, Chun Jye Chew, Valerie Tags: Review Article Source Type: research

Role of Biomarkers in Guiding Cure of Viral Hepatitis B
Semin Liver Dis DOI: 10.1055/s-0039-3401031Chronic hepatitis B (CHB) virus infection is a global public health threat affecting approximately 257 million individuals worldwide. Hepatitis B surface antigen (HBsAg) loss has been the classic endpoint to define functional cure and decrease the large pool of individuals with CHB. Current treatments with nucleos(t)ide analogues persistently suppress hepatitis B virus (HBV) deoxyribonucleic acid in most CHB patients, but rarely achieve functional cure. New viral biomarkers, such as quantitative HBsAg, hepatitis B core-related antigen, and HBV ribonucleic acid, and combinations of...
Source: Seminars in Liver Disease - December 5, 2019 Category: Gastroenterology Authors: Buti, Maria Riveiro-Barciela, Mar Rodr íguez-Frías, Francisco Tabernero, David Esteban, Rafael Tags: Review Article Source Type: research

Emerging Role of Palliative Care in Patients with Advanced Liver Disease
Semin Liver Dis DOI: 10.1055/s-0039-3400259Advanced liver disease is increasing in mortality and morbidity worldwide, as a result of growing alcohol consumption, obesity, and viral hepatitis infection. Alongside efforts to reduce these factors, it is clear that we must identify the considerable palliative care needs of these patients in order to improve quality of life and reduce symptom burden. Our review focuses on the current state of palliative and end-of-life care for patients with advanced liver disease, the significant associated symptom burden in this disease group, identified level of involvement and potential ben...
Source: Seminars in Liver Disease - November 15, 2019 Category: Gastroenterology Authors: Jordan, Roberta I. Tandon, Puneeta Tags: Review Article Source Type: research

Epidemiology of Liver Cancer in Africa: Current and Future Trends
We present a narrative review of HCC in Africa, discussing present and future trends. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease)
Source: Seminars in Liver Disease - November 14, 2019 Category: Gastroenterology Authors: Okeke, Edith Davwar, Pantong Mark Roberts, Lewis Sartorius, Kurt Spearman, Wendy Malu, Abraham Duguru, Mary Tags: Review Article Source Type: research

Neutrophil Extracellular Traps and Liver Disease
Semin Liver Dis DOI: 10.1055/s-0039-3399562Neutrophil extracellular traps, or NETs, are heterogenous, filamentous structures which consist of extracellular DNA, granular proteins, and histones. NETs are extruded by a neutrophil in response to various stimuli. Although NETs were initially implicated in immune defense, subsequent studies have implicated NETs in a spectrum of disease processes, including autoimmune disease, thrombosis, and cancer. NETs also contribute to the pathogenesis of several common liver diseases, including alcohol-associated liver disease and portal hypertension. Although there is much interest in the...
Source: Seminars in Liver Disease - November 14, 2019 Category: Gastroenterology Authors: Hilscher, Moira B. Shah, Vijay H. Tags: Review Article Source Type: research

Early Liver Transplantation in Acute Alcoholic Hepatitis
Semin Liver Dis DOI: 10.1055/s-0039-3399560Alcohol-related liver disease (ALD) is currently the leading indication for liver transplantation in the United States. Among patients with ALD, those with acute alcoholic hepatitis who do not respond to medical treatment have a 6-month mortality of 70% without transplantation. Despite the high mortality, the majority of patients will not be eligible for transplant, given that most centers follow the 6-month abstinence rule. A handful of centers in Europe and the United States perform early liver transplantation (
Source: Seminars in Liver Disease - November 11, 2019 Category: Gastroenterology Authors: Haugen, Christine E. Cameron, Andrew M. Tags: Review Article Source Type: research

Epidemiology of Liver Cancer in Latin America: Current and Future Trends
Semin Liver Dis DOI: 10.1055/s-0039-3399561Over 38,000 cases of hepatocellular carcinoma (HCC) are estimated to occur in Latin America annually. The region is characterized by sociocultural heterogeneity and economic disparities, which impose barriers in addressing this major health issue. A significant proportion of patients are still diagnosed in the later stages of the disease, although efforts to implement effective screening programs have been reported by referral centers. While viral hepatitis remains the predominant etiology of liver disease among HCC cases in Latin America, a high prevalence of fatty liver disease ...
Source: Seminars in Liver Disease - November 11, 2019 Category: Gastroenterology Authors: Carrilho, Flair Jose Paranagu á-Vezozzo, Denise Cerqueira Chagas, Aline Lopes Alencar, Regiane Saraiva de Souza Melo da Fonseca, Leonardo Gomes Tags: Review Article Source Type: research

Mechanotransduction in Liver Diseases
Semin Liver Dis DOI: 10.1055/s-0039-3399502Chronic liver diseases, such as fibrosis and cancer, lead to a rigid or stiff liver because of perpetual activation of hepatic stellate cells or portal fibroblasts into matrix-producing myofibroblasts. Mechanical forces, as determined by the mechanical properties of extracellular matrix or pressure of circulating blood flow/shear stress, are sensed by mechanoreceptors at the plasma membrane and transmitted into a cell to impact cell function. This process is termed as mechanotransduction. This review includes basic knowledge regarding how external forces are sensed, amplified, and...
Source: Seminars in Liver Disease - November 4, 2019 Category: Gastroenterology Authors: Kang, Ningling Tags: Review Article Source Type: research

Cholemic Nephropathy Reloaded
Semin Liver Dis DOI: 10.1055/s-0039-1698826Acute kidney injury (AKI) is a dreaded complication in patients with liver disease and jaundice, since it is associated with significant morbidity and mortality. Cholemic nephropathy (CN) is thought to represent a widely underestimated important cause of AKI in advanced liver diseases with jaundice. The umbrella term CN describes impaired renal function along with histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed primarily toward distal nephron segments. In cholestasis, biliary constituents may be excreted via the kidn...
Source: Seminars in Liver Disease - October 18, 2019 Category: Gastroenterology Authors: Fickert, Peter Rosenkranz, Alexander R. Tags: Review Article Source Type: research

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review
Semin Liver Dis DOI: 10.1055/s-0039-1697617Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptib...
Source: Seminars in Liver Disease - September 19, 2019 Category: Gastroenterology Authors: Lleo, Ana Leung, Patrick S.C. Hirschfield, Gideon M. Gershwin, Eric M. Tags: Review Article Source Type: research

Peculiarities of Cirrhosis due to Nonalcoholic Steatohepatitis (NASH)
Semin Liver Dis DOI: 10.1055/s-0039-1697616The prevalence of cirrhosis due to nonalcoholic steatohepatitis (NASH) has increased 2.5-fold in the United States in the last decade. These patients pose new challenges to hepatologists given their older age and higher frequency of coexisting metabolic diseases such as obesity and diabetes compared with other etiologies of liver disease. Patients with NASH cirrhosis are at higher risk for renal and cardiovascular disease, and the presence of these extrahepatic comorbidities has a significant impact on outcomes and survival. This review outlines how NASH cirrhosis differs from oth...
Source: Seminars in Liver Disease - September 19, 2019 Category: Gastroenterology Authors: El-Sherif, Omar Armstrong, M.J. Tags: Review Article Source Type: research

Management of Lifestyle Factors in Individuals with Cirrhosis: A Pragmatic Review
Semin Liver Dis DOI: 10.1055/s-0039-1696639Lifestyle-related factors are major determinants/modifiers of prognosis in patients with cirrhosis. Accumulating evidence indicates that malnutrition, obesity, sedentary lifestyle, alcohol and smoking habits, and likely poor oral hygiene can increase the risk of progression of the disease, and some of them are linked to higher risk of hepatocellular carcinoma. Importantly, lifestyle-related factors can be largely corrected, and as such they represent an attractive approach to be added to etiological and pharmacological therapy in patients with cirrhosis. Nonetheless, lifestyle is ...
Source: Seminars in Liver Disease - August 30, 2019 Category: Gastroenterology Authors: Tandon, Puneeta Berzigotti, Annalisa Tags: Review Article Source Type: research

Assessment and Management of Infection in Alcoholic Hepatitis
Semin Liver Dis DOI: 10.1055/s-0039-1693402Severe alcoholic hepatitis (SAH) is a condition characterized by jaundice and liver failure that develops after heavy and prolonged alcohol consumption. Infection frequently complicates the natural history of the disease and is independently associated with mortality. Objective recognition and recording of infection are therefore essential in the evaluation of therapeutic interventions and for antibiotic stewardship. This review will evaluate infections that complicate SAH at admission and beyond. Factors that associate with the development of infection will be identified and clin...
Source: Seminars in Liver Disease - August 1, 2019 Category: Gastroenterology Authors: Vergis, Nikhil Atkinson, Stephen R. Thursz, Mark R. Tags: Review Article Source Type: research

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 22, 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 19, 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 17, 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 ...
Source: Seminars in Liver Disease - July 17, 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 4, 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 relev...
Source: Seminars in Liver Disease - July 2, 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 2, 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 26, 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...
Source: Seminars in Liver Disease - June 26, 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, ...
Source: Seminars in Liver Disease - June 26, 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 21, 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 21, 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 21, 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 17, 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 17, 2019 Category: Gastroenterology Authors: Lillemoe, Heather A. Brudvik, Kristoffer W. Vauthey, Jean-Nicolas Tags: Review Article Source Type: research

Assessment of Serious Acute and Chronic Idiosyncratic Drug-Induced Liver Injury in Clinical Practice
Semin Liver Dis DOI: 10.1055/s-0039-1685519Drug-induced liver injury (DILI) is the leading cause of acute liver failure (ALF) in developed countries. The extremely variable phenotype of DILI, both in presentation and in severity, is one of the distinctive characteristics of the disease and one of the major challenges that hepatologists face when assessing hepatotoxicity cases. A new Hy's law that more accurately predicts the risk of ALF related to DILI has been proposed and validated. Other prognostic scoring algorithms for the early identification of DILI patients who may go on to develop ALF have been developed as it is ...
Source: Seminars in Liver Disease - May 2, 2019 Category: Gastroenterology Authors: Bessone, Fernando Robles-Diaz, Mercedes Hernandez, Nelia Medina-Caliz, Inmaculada Lucena, M. Isabel Andrade, Raul J. Tags: Review Article Source Type: research

Magnetic Resonance Imaging in Primary Sclerosing Cholangitis —Current State and Future Directions
Semin Liver Dis DOI: 10.1055/s-0039-1687853Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and fibrosis leading to bile duct strictures, cirrhosis, and carries an increased risk of hepatobiliary malignancies. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is the imaging modality of choice in PSC. As an evolving technology, MRI has other potential applications in the care and study of those patients with PSC. In this review, the authors aim to provide a technical overview on MRI/MRCP and related technologies, summariz...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Zenouzi, Roman Welle, Christopher L. Venkatesh, Sudhakar K. Schramm, Christoph Eaton, John E. Tags: Review Article Source Type: research

Lipid Droplet Formation and Lipophagy in Fatty Liver Disease
Semin Liver Dis DOI: 10.1055/s-0039-1685524Lipid droplets (LDs) are key sites of neutral lipid storage that can be found in all cells. Metabolic imbalances between the synthesis and degradation of LDs can result in the accumulation of significant amounts of lipid deposition, a characteristic feature of hepatocytes in patients with fatty liver disease, a leading indication for liver transplant in the United States. In this review, the authors highlight new literature related to the synthesis and autophagic catabolism of LDs, discussing key proteins and machinery involved in these processes. They also discuss recent findings...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Schulze, Ryan J. McNiven, Mark A. Tags: Review Article Source Type: research

Retreatment of Hepatitis C Virus-Infected Patients with Direct-Acting Antiviral Failures
This article discusses virological failure rates with the successive waves of HCV combination regimens, the reasons for failure, the role of HCV resistance, and current retreatment options. The triple combination of sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks is the first-line retreatment strategy in patients previously exposed to DAAs. Difficult-to-retreat patients may benefit from the combination of sofosbuvir plus glecaprevir/pibrentasvir and/or the addition of ribavirin and/or longer retreatment duration. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals:...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Pawlotsky, Jean-Michel Tags: Review Article Source Type: research

Mutational Processes in Hepatocellular Carcinoma: The Story of Aristolochic Acid
Semin Liver Dis DOI: 10.1055/s-0039-1685516Each hepatocellular carcinoma displays dozens of mutations in driver and passenger genes. The analysis of the types of substitutions and their trinucleotide context defines mutational signatures that recapitulate the endogenous and exogenous mutational processes operative in tumor cells. Aristolochic acid is present in plants from the genus Aristolochia and causes chronic nephropathy. Moreover, aristolochic acid has genotoxic properties responsible for the occurrence of urothelial carcinoma. Metabolites of aristolochic acid form DNA adducts on adenine residues leading to a specifi...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Nault, Jean-Charles Letouz é, Eric Tags: Review Article Source Type: research

Immunosuppressive Drug Levels in Liver Transplant Recipients: Impact in Decision Making
Semin Liver Dis DOI: 10.1055/s-0039-1688443To prevent rejection, liver transplant providers largely base their management decisions on their clinical impression and pharmacokinetics. Clinical impression relies on assessing graft function, liver enzymes, and biopsy. High immunosuppressive drug levels, although minimizing rejection, are related to significant side effects such as nephrotoxicity and metabolic syndrome, contributing to long-term morbidity and mortality. Similarly, levels that are lower than necessary can decrease the rate of side effects with a potential toll on rejection and graft survival. Herein, the author...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Kourkoumpetis, Themistoklis Levitsky, Josh Tags: Review Article Source Type: research

Macrophages as Key Players during Adipose Tissue –Liver Crosstalk in Nonalcoholic Fatty Liver Disease
Semin Liver Dis DOI: 10.1055/s-0039-1687851Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that could lead to serious health problems including liver failure, cancer, or death. The term NAFLD includes a spectrum of disease states with histological features ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A key aspect within this research field is the identification of pathogenic factors that trigger inflammation, thus fueling the transition from nonalcoholic fatty liver to NASH. These inflammatory triggers may originate from within the liv...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Korf, Hannelie Boesch, Markus Meelberghs, Lore van der Merwe, Schalk Tags: Review Article Source Type: research

Long-Term Impact of Direct-Acting Antiviral Agent Therapy in HCV Cirrhosis: Critical Review
Semin Liver Dis DOI: 10.1055/s-0039-1685538More than 70 million people are chronically infected with hepatitis C virus (HCV) worldwide. Chronic hepatitis C is associated with progressive liver fibrosis, which can result in cirrhosis, liver failure, and hepatocellular carcinoma (HCC). HCV-related liver disease has been the most common indication for liver transplantation in the past decade. The development of direct-acting antiviral agents (DAAs) that are simple, well-tolerated, and highly effective means that most people living with hepatitis C can now be cured, leading the World Health Organization to set targets for redu...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Fehily, Sasha R. Papaluca, Tim Thompson, Alexander J. Tags: Review Article Source Type: research

Clinical Trials in PBC Going Forward
Semin Liver Dis DOI: 10.1055/s-0039-1687852New treatments for primary biliary cholangitis (PBC) are progressively emerging, including first and second generations of farnesoid X receptor and peroxisome proliferator-activated receptors agonists. Even though ursodeoxycholic acid monotherapy remains the standard of care treatment for PBC, these additional therapeutic options, already or soon to be available, lead us to revise our priorities and strategies with respect to future clinical trials. The present article is a personal view of where we currently stand in this field and where and how we should be going to achieve new ...
Source: Seminars in Liver Disease - April 30, 2019 Category: Gastroenterology Authors: Corpechot, Christophe Tags: Review Article Source Type: research

Erratum: Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases
Semin Liver Dis DOI: 10.1055/s-0039-1688409 Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Full text (Source: Seminars in Liver Disease)
Source: Seminars in Liver Disease - April 16, 2019 Category: Gastroenterology Authors: Patten, Daniel A. Shepherd, Emma L. Weston, Christopher Shetty, Shishir Tags: Erratum Source Type: research

Direct-Acting Oral Anticoagulants (DOACs) in Cirrhosis and Cirrhosis-Associated Portal Vein Thrombosis
This article reviews the current Food and Drug Administration-approved DOACs, hepatic metabolism of DOACs, pharmacokinetics of DOACs in patients with cirrhosis, safety of DOACs (including bleeding, hepatotoxicity, and pregnancy), current treatment guidelines for PVT in cirrhosis, and studies evaluating the use of DOACs in cirrhosis and for the treatment of PVT in cirrhosis. The potential use of DOACs for PVT primary prophylaxis in at-risk patients with cirrhosis and the possible antifibrotic effects of DOACs are also discussed. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJ...
Source: Seminars in Liver Disease - April 12, 2019 Category: Gastroenterology Authors: Weinberg, Ethan M. Palecki, Julia Reddy, K. Rajender Tags: Review Article Source Type: research

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications
Semin Liver Dis DOI: 10.1055/s-0039-1678728Occult hepatitis B infection (OBI) is a status of undetectable serum hepatitis B surface antigen (HBsAg) yet detectable serum and/or intrahepatic hepatitis B virus (HBV) DNA. Mutations in the preS1, preS2, and S regions of the HBsAg gene may result in undetectable HBsAg. OBI may either result from a self-limiting acute hepatitis, or in patients with chronic hepatitis B who achieved HBsAg seroclearance, which refers to the loss of detectability of serum HBsAg with or without antibody to HBsAg (anti-HBs) in chronic hepatitis B (CHB) patients. HBsAg seroclearance contributes to a sig...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Yip, Terry Cheuk-Fung Wong, Grace Lai-Hung Tags: Review Article Source Type: research

Genetics of Nonalcoholic Fatty Liver Disease: From Pathogenesis to Therapeutics
Semin Liver Dis DOI: 10.1055/s-0039-1679920Here, the authors review the remarkable genetic discoveries that have illuminated the biology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The authors integrate genes associated with NAFLD and NASH into regulatory pathways to elucidate the disease pathogenesis. They review the evidence for molecular mediators of chronic liver damage, which suggests that convergent pathophenotypes, including inflammation and fibrosis, share common genetic modifiers. They further demonstrate that genes involved in the genetic susceptibility of NAFLD and NASH p...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Sookoian, Silvia Pirola, Carlos J. Tags: Review Article Source Type: research

Balloon Tamponade and Esophageal Stenting for Esophageal Variceal Bleeding in Cirrhosis: A Systematic Review and Meta-analysis
Semin Liver Dis DOI: 10.1055/s-0039-1678726Failure to control variceal bleeding with current recommendations occurs in 10 to 20% of cases. This systematic review and meta-analysis analyzes the experience, results, and complications of “bridge” therapies for failure to control acute variceal bleeding: balloon tamponade and esophageal stents. The main outcomes assessed were failure to control bleeding and mortality in the short-term and medium-term follow-up, and adverse events. Balloon tamponade studies had a pooled rate of short-term failure to control bleeding of 35.5%, and adverse events in over 20% of cases;...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Rodrigues, Susana G. C árdenas, Andrés Escorsell, Àngels Bosch, Jaime Tags: Review Article Source Type: research

Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases
Semin Liver Dis DOI: 10.1055/s-0039-1678727Immune dysregulation and accumulation of leukocytes is a hallmark of adult chronic liver diseases. Progressive hepatic inflammation can lead to fibrosis and cirrhosis with a high risk of liver failure or hepatocellular cancer (HCC). Recent advances have been made in the treatment of liver disease including the development of highly effective antiviral therapy for hepatitis C and the potential of immunotherapy for HCC. Despite this, the majority of other chronic liver diseases including alcoholic liver disease, fatty liver disease, and cholestatic diseases do not respond to convent...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Patten, Daniel A. Shepherd, Emma L. Weston, Christopher J. Shetty, Shishir Tags: Review Article Source Type: research

Endoplasmic Reticulum Stress in Metabolic Liver Diseases and Hepatic Fibrosis
Semin Liver Dis DOI: 10.1055/s-0039-1681032Endoplasmic reticulum (ER) stress is a major contributor to liver disease and hepatic fibrosis, but the role it plays varies depending on the cause and progression of the disease. Furthermore, ER stress plays a distinct role in hepatocytes versus hepatic stellate cells (HSCs), which adds to the complexity of understanding ER stress and its downstream signaling through the unfolded protein response (UPR) in liver disease. Here, the authors focus on the current literature of ER stress in nonalcoholic and alcoholic fatty liver diseases, how ER stress impacts hepatocyte injury, and th...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Maiers, Jessica L. Malhi, Harmeet Tags: Review Article Source Type: research

Prevention of Hepatocellular Carcinoma by Statins: Clinical Evidence and Plausible Mechanisms
Semin Liver Dis DOI: 10.1055/s-0039-1679956Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used to treat hypercholesterolemia for primary and secondary prevention of cardiovascular disease. Statins inhibit HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and modulate the downstream signaling of the mevalonate pathway. In addition to the primary effect, the antitumor effect of statins can be associated with mevalonate pathway-mediated and nonmevalonate pathway-mediated mechanisms, which improve endothelial function and lead to proapoptotic, antiproliferative, a...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Kim, Gyuri Kang, Eun Seok Tags: Review Article Source Type: research

Liver Cancer Gene Discovery Using Gene Targeting, Sleeping Beauty, and CRISPR/Cas9
Semin Liver Dis DOI: 10.1055/s-0039-1678725Hepatocellular carcinoma (HCC) is a devastating and prevalent cancer with limited treatment options. Technological advances have enabled genetic screens to be employed in HCC model systems to characterize genes regulating tumor initiation and growth. Relative to traditional methods for studying cancer biology, such as candidate gene approaches or expression analysis, genetic screens have several advantages: they are unbiased, with no a priori selection; can directly annotate gene function; and can uncover gene–gene interactions. In HCC, three main types of screens have been ...
Source: Seminars in Liver Disease - March 25, 2019 Category: Gastroenterology Authors: Kieckhaefer, Julia E. Maina, Flavio Wells, Rebecca G. Wangensteen, Kirk J. Tags: Review Article Source Type: research