Novel Mechanisms for Resolution of Liver Inflammation: Therapeutic Implications
Semin Liver Dis DOI: 10.1055/s-0041-1723031Traditional concepts have classically viewed resolution of inflammation as a passive process yet insight into the pathways by which inflammation is resolved has challenged this idea. Resolution has been revealed as a highly dynamic and active event that is essential to counteract the dysregulated inflammatory response that drives diverse disease states. Abrogation of the hepatic inflammatory response through the stimulation of proresolving mechanisms represents a new paradigm in the setting of chronic inflammatory-driven liver diseases. Elucidation of the role of different cells o...
Source: Seminars in Liver Disease - March 24, 2021 Category: Gastroenterology Authors: Kaufmann, Benedikt Reca, Agustina Kim, Andrea D. Feldstein, Ariel E. Tags: Review Article Source Type: research

Assessing Toxicity in Drug Trials in Liver Disease
Semin Liver Dis DOI: 10.1055/s-0041-1723030Since the early trials in viral hepatitis, more and more new drugs are being tested for use in various liver diseases. Since drug hepatotoxicity is a major cause of drugs under investigation not making it to market, the assessment of drug-induced liver injury in clinical trials of new drugs is crucial. This review will focus on the systems that are used to assess drug-induced liver injury in clinical trials and will discuss how some of these criteria are inappropriate or inaccurate in this function together with suggestions for improvement. [...] Thieme Medical Publishers, Inc. 33...
Source: Seminars in Liver Disease - March 8, 2021 Category: Gastroenterology Authors: Sherman, Morris Tags: Review Article Source Type: research

Gut –Liver Axis in Nonalcoholic Fatty Liver Disease: the Impact of the Metagenome, End Products, and the Epithelial and Vascular Barriers
Semin Liver Dis DOI: 10.1055/s-0041-1723752Nonalcoholic fatty liver disease (NAFLD) is a systemic, dynamic, heterogeneous, and multiaxis entity, the pathogenesis of which is still uncertain. The gut–liver axis is regulated and stabilized by a complex network encompassing a metabolic, immune, and neuroendocrine cross-talk between the gut, the microbiota, and the liver. Changes in the gut–liver axis affect the metabolism of lipids and carbohydrates in the hepatocytes, and they impact the balance of inflammatory mediators and cause metabolic deregulation, promoting NAFLD and its progression to nonalcoholic steatoh...
Source: Seminars in Liver Disease - March 8, 2021 Category: Gastroenterology Authors: Gil-G ómez, Antonio Brescia, Paola Rescigno, Maria Romero-G ómez, Manuel Tags: Review Article Source Type: research

Organoids for the Study of Liver Cancer
Semin Liver Dis DOI: 10.1055/s-0040-1719176Liver cancer is the second most lethal malignancy worldwide. Cell lines and murine models are the most common tools for modeling human liver carcinogenesis. Most recently, organoids with a three-dimensional structure derived from primary tissues or cells have been applied to liver cancer research. Organoids can be generated from induced pluripotent stem cells, embryonic or adult, healthy or diseased tissues. In particular, liver organoids have been widely employed in mechanistic studies aimed at delineating the molecular pathways responsible for hepatocarcinogenesis. The introduct...
Source: Seminars in Liver Disease - February 9, 2021 Category: Gastroenterology Authors: Wang, Haichuan Calvisi, Diego F. Chen, Xin Tags: Review Article Source Type: research

Management of Portal Vein Thrombosis in Cirrhosis
Semin Liver Dis DOI: 10.1055/s-0040-1722260While portal vein thrombosis (PVT) is a frequently encountered complication in the cirrhosis population, its management can be challenging for even the most experienced clinicians. Multiple factors must be considered with regards to management, including the degree of underlying portal hypertension and liver dysfunction, risks of therapies including anticoagulation and transjugular intrahepatic portosystemic shunt placement, and extent of the thrombosis. Interpreting the available literature to determine the best treatment strategy for any individual patient can be especially chal...
Source: Seminars in Liver Disease - February 9, 2021 Category: Gastroenterology Authors: Stotts, Matthew J. Wentworth, Brian J. Northup, Patrick G. Tags: Review Article Source Type: research

Insights into the Role of Granulocyte Colony-Stimulating Factor in Severe Alcoholic Hepatitis
Semin Liver Dis DOI: 10.1055/s-0040-1719177Alcohol use disorder is the predominant cause of chronic liver disease globally. The standard of care for the treatment of alcoholic hepatitis, corticosteroids, has been shown to provide a therapeutic response in ∼60% of carefully selected patients with a short-term survival benefit. The patients who do not respond to steroids, or are ineligible due to infections or very severe disease, have little options other than liver transplantation. There is, thus, a large unmet need for new therapeutic strategies for this large and sick group of patients. Granulocyte colony stimulating...
Source: Seminars in Liver Disease - February 9, 2021 Category: Gastroenterology Authors: Kedarisetty, Chandan Kumar Kumar, Anupam Sarin, Shiv Kumar Tags: Review Article Source Type: research

Cellular Senescence in Liver Disease and Regeneration
Semin Liver Dis DOI: 10.1055/s-0040-1722262Cellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanis...
Source: Seminars in Liver Disease - February 9, 2021 Category: Gastroenterology Authors: Ferreira-Gonzalez, Sofia Rodrigo-Torres, Daniel Gadd, Victoria L. Forbes, Stuart J. Tags: Review Article Source Type: research

Molecular Mechanisms of Hepatoblastoma
Semin Liver Dis DOI: 10.1055/s-0040-1722645Hepatoblastoma (HB) is the predominant primary liver tumor in children. While the prognosis is favorable when the tumor can be resected, the outcome is dismal for patients with progressed HB. Therefore, a better understanding of the molecular mechanisms responsible for HB is imperative for early detection and effective treatment. Sequencing analysis of human HB specimens unraveled the pivotal role of Wnt/β-catenin pathway activation in this disease. Nonetheless, β-catenin activation alone does not suffice to induce HB, implying the need for additional alterations. Pertur...
Source: Seminars in Liver Disease - January 20, 2021 Category: Gastroenterology Authors: Zhang, Yi Solinas, Antonio Cairo, Stefano Evert, Matthias Chen, Xin Calvisi, Diego F. Tags: Review Article Source Type: research

Intrahepatic Cholestasis of Pregnancy: Natural History and Current Management
Semin Liver Dis DOI: 10.1055/s-0040-1722264Intrahepatic cholestasis of pregnancy (ICP) is a common disorder in the second half of pregnancy characterized by pruritus and elevated serum bile acids (BAs) with spontaneous resolution after delivery. ICP carries a risk of adverse effects on the fetus which correlates with the degree of BA elevation. ICP occurs in genetically susceptible women as the reproductive hormones increase during pregnancy. Ursodeoxycholic acid is still considered the first-line treatment for ICP though it is of unproven benefit in preventing adverse effects on the fetus. Fetal complications, such as sti...
Source: Seminars in Liver Disease - January 20, 2021 Category: Gastroenterology Authors: Roediger, Rebecca Fleckenstein, Jaquelyn Tags: Review Article Source Type: research

The Key Role of Staging Definitions for Assessment of Downstaging for Hepatocellular Carcinoma
Semin Liver Dis DOI: 10.1055/s-0040-1716565The success of liver transplant (LT) for hepatocellular carcinoma (HCC) is dependent on accurate tumor staging using validated imaging criteria, and adherence to acceptable criteria based on tumor size and number. Other factors including α-fetoprotein (AFP) and response to local regional therapy (LRT) have now played a larger role in candidate selection. Tumor downstaging is defined as reduction in the size of viable tumors using LRT to meet acceptable criteria for LT, and serves as a selection tool for a subgroup of HCC with more favorable biology. The application of tumor ...
Source: Seminars in Liver Disease - January 14, 2021 Category: Gastroenterology Authors: Yao, Francis Y. Fidelman, Nicholas Mehta, Neil Tags: Review Article Source Type: research

New Developments in Microbiome in Alcohol-Associated and Nonalcoholic Fatty Liver Disease
Semin Liver Dis DOI: 10.1055/s-0040-1719174Alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the ...
Source: Seminars in Liver Disease - January 14, 2021 Category: Gastroenterology Authors: Hartmann, Phillipp Schnabl, Bernd Tags: Review Article Source Type: research

Wearables, Physical Activity, and Exercise Testing in Liver Disease
Semin Liver Dis DOI: 10.1055/s-0040-1716564Physical inactivity is a major cause of deterioration in all forms of advanced liver disease. It is especially important as a driver of the components of the metabolic syndrome, with nonalcoholic fatty liver disease rapidly becoming the dominant cause of liver-related death worldwide. Growing realization of the health benefits of moderate-to-vigorous physical activity has captured the interest of persons who desire to improve their health, including those at risk for chronic liver injury. They are increasingly adopting wearable activity trackers to measure the activity that they s...
Source: Seminars in Liver Disease - January 14, 2021 Category: Gastroenterology Authors: Dunn, Michael A. Kappus, Matthew R. Bloomer, Pamela M. Duarte-Rojo, Andres Josbeno, Deborah A. Jakicic, John M. Tags: Review Article Source Type: research

Deciphering Tumor Heterogeneity in Hepatocellular Carcinoma (HCC) —Multi-Omic and Singulomic Approaches
Semin Liver Dis DOI: 10.1055/s-0040-1722261Tumor heterogeneity, a key hallmark of hepatocellular carcinomas (HCCs), poses a significant challenge to developing effective therapies or predicting clinical outcomes in HCC. Recent advances in next-generation sequencing-based multi-omic and single cell analysis technologies have enabled us to develop high-resolution atlases of tumors and pull back the curtain on tumor heterogeneity. By combining multiregion targeting sampling strategies with deep sequencing of the genome, transcriptome, epigenome, and proteome, several studies have revealed novel mechanistic insights into tumor...
Source: Seminars in Liver Disease - January 14, 2021 Category: Gastroenterology Authors: Dhanasekaran, Renumathy Tags: Review Article Source Type: research

Role of Multidisciplinary Care in the Management of Hepatocellular Carcinoma
Semin Liver Dis DOI: 10.1055/s-0040-1719178Despite advances in treatment options for hepatocellular carcinoma (HCC), 5-year survival for HCC remains below 20%. This poor survival is multifactorial but is partly related to underuse of curative treatment in clinical practice. In light of growing treatment options, delivered by different types of providers, optimal management requires input from multiple specialties. A multidisciplinary approach has been evolving over the past couple of decades, bringing different specialists together to develop a therapeutic plan to treat and manage HCC, which significantly increases timely ...
Source: Seminars in Liver Disease - January 14, 2021 Category: Gastroenterology Authors: Byrd, Kia Alqahtani, Saleh Yopp, Adam C. Singal, Amit G. Tags: Review Article Source Type: research

Cell Therapy for Liver Disease: From Promise to Reality
Semin Liver Dis 2020; 40: 411-426 DOI: 10.1055/s-0040-1717096Over the last decade, there has been a considerable progress in the development of cell therapy products for the treatment of liver diseases. The quest to generate well-defined homogenous cell populations with defined mechanism(s) of action has enabled the progression from use of autologous bone marrow stem cells comprising of heterogeneous cell populations to allogeneic cell types such as monocyte-derived macrophages, regulatory T cells, mesenchymal stromal cells, macrophages, etc. There is growing evidence regarding the multiple molecular mechanisms pivotal to ...
Source: Seminars in Liver Disease - December 24, 2020 Category: Gastroenterology Authors: Khan, Sheeba Khan, Reenam S. Newsome, Philip N. Tags: Review Article Source Type: research

Differential Roles for Diploid and Polyploid Hepatocytes in Acute and Chronic Liver Injury
Semin Liver Dis DOI: 10.1055/s-0040-1719175Hepatocytes are the primary functional cells of the liver that perform essential roles in homeostasis, regeneration, and injury. Most mammalian somatic cells are diploid and contain pairs of each chromosome, but there are also polyploid cells containing additional sets of chromosomes. Hepatocytes are among the best described polyploid cells, with polyploids comprising more than 25 and 90% of the hepatocyte population in humans and mice, respectively. Cellular and molecular mechanisms that regulate hepatic polyploidy have been uncovered, and in recent years, diploid and polyploid h...
Source: Seminars in Liver Disease - December 14, 2020 Category: Gastroenterology Authors: Wilkinson, Patrick D. Duncan, Andrew W. Tags: Review Article Source Type: research

Aging and Chronic Liver Disease
Semin Liver Dis 2020; 40: 373-384 DOI: 10.1055/s-0040-1715446Aging increases the incidence of chronic liver disease (CLD), worsens its prognosis, and represents the predominant risk factor for its development at all different stages. The hepatic sinusoid, which is fundamental for maintaining liver homeostasis, is composed by hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic macrophages. During CLD progression, hepatic cells suffer deregulations in their phenotype, which ultimately lead to disease development. The effects of aging on the hepatic sinusoid phenotype and function are not well...
Source: Seminars in Liver Disease - November 20, 2020 Category: Gastroenterology Authors: Maeso-D íaz, Raquel Gracia-Sancho, Jordi Tags: Review Article Source Type: research

Evolution of Liver Transplant Selection Criteria and U.S. Allocation Policy for Patients with Hepatocellular Carcinoma
Semin Liver Dis DOI: 10.1055/s-0040-1709492Liver transplantation (LT) is an optimal treatment option for early-stage unresectable hepatocellular carcinoma (HCC) in patients with cirrhosis as it provides a treatment for underlying liver disease as well as a decreased incidence of recurrent cancer compared with alternative treatment strategies. A primary barrier to LT for HCC is the critical shortage of available liver allografts. The system of prioritization and access to deceased donor transplantation for patient with HCC in the United States has continued to evolve, while variable approaches including no additional priori...
Source: Seminars in Liver Disease - September 16, 2020 Category: Gastroenterology Authors: Heimbach, Julie K. Tags: Review Article Source Type: research

Histological Endpoints for Nonalcoholic Steatohepatitis Trials: Lights and Shadows
Semin Liver Dis DOI: 10.1055/s-0040-1709491Nonalcoholic steatohepatitis (NASH) with liver fibrosis is an increasingly important cause of liver-related morbidity and mortality. A diagnosis of NASH can only be made using liver biopsy. Liver histology also forms the endpoint for the expedited licensing strategies that have been approved by regulators to allow patients with NASH access to treatment before the impact of these on clinical outcomes is known. Validation of these histological surrogate endpoints is critical for the ongoing development of new therapies for NASH. The use of liver biopsy to define both trial entry and...
Source: Seminars in Liver Disease - September 8, 2020 Category: Gastroenterology Authors: Rowe, Ian A Tags: Review Article Source Type: research

The Role of Lymphatics in Cholestasis: A Comprehensive Review
Semin Liver Dis DOI: 10.1055/s-0040-1713675Cholestatic liver disease affects millions of people worldwide and stems from a plethora of causes such as immune dysfunction, genetics, cancerous growths, and lifestyle choices. While not considered a classical lymphatic organ, the liver plays a vital role in the lymph system producing up to half of the body's lymph per day. The lymphatic system is critical to the health of an organism with its networks of vessels that provide drainage for lymphatic fluid and routes for surveilling immune cells. Cholestasis results in an increase of inflammatory cytokines, growth factors, and inf...
Source: Seminars in Liver Disease - September 8, 2020 Category: Gastroenterology Authors: O'Brien, April Gasheva, Olga Alpini, Gianfranco Zawieja, David Gashev, Anatoliy Glaser, Shannon Tags: Review Article Source Type: research

Direct or Collateral Liver Damage in SARS-CoV-2 –Infected Patients
Semin Liver Dis 2020; 40: 321-330 DOI: 10.1055/s-0040-1715108Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the ...
Source: Seminars in Liver Disease - September 3, 2020 Category: Gastroenterology Authors: Lizardo-Thiebaud, Maria J. Cervantes-Alvarez, Eduardo Limon-de la Rosa, Nathaly Tejeda-Dominguez, Farid Palacios-Jimenez, Mildred M éndez-Guerrero, Osvely Delaye-Martinez, Marco Rodriguez-Alvarez, Fatima Romero-Morales, Beatriz Liu, Wei-Hui Huang, Christ Tags: Review Article Source Type: research

Alcohol Use Disorder and Hepatitis C Prevention and Care in People Who Inject Drugs: The State of Play
Semin Liver Dis DOI: 10.1055/s-0040-1716343Safe and effective treatment with direct-acting antivirals (DAAs) has ushered in an era in which hepatitis C virus (HCV) elimination, as set out by the World Health Organization, is possible. However, alcohol use disorder (AUD) has the potential to reduce the benefits of prevention interventions and reduce access to and continuity of HCV care in at-risk populations, such as people who inject drugs (PWID). We review the literature on the consequences of AUD on the effectiveness of HCV prevention and the cascade of care in PWID and provide recommendations for future research in the ...
Source: Seminars in Liver Disease - August 25, 2020 Category: Gastroenterology Authors: Marcellin, Fabienne Jaquet, Antoine Lazarus, Jeffrey V. Molina, Patricia Carrieri, Patrizia Tags: Review Article Source Type: research

Simplification of Care for Chronic Hepatitis C Virus Infection
Semin Liver Dis DOI: 10.1055/s-0040-1713657In 2016, the World Health Organization (WHO) set a target for eliminating viral hepatitis as a major public health threat by 2030. However, while today's highly effective and well-tolerated pangenotypic direct-acting antiviral regimens have maximized simplification of hepatitis C virus (HCV) treatment, there remain a plethora of barriers to HCV screening, diagnosis, and linkage to care. As of 2017, only 19% of the estimated 71 million individuals living with chronic HCV worldwide were diagnosed and in 2015 to 2016, only 21% of diagnosed individuals had accessed treatment. Simplifi...
Source: Seminars in Liver Disease - July 27, 2020 Category: Gastroenterology Authors: Pawlotsky, Jean-Michel Ramers, Christian B. Dillon, John F. Feld, Jordan J. Lazarus, Jeffrey V. Tags: Review Article Source Type: research

Noninvasive Diagnostics for Portal Hypertension: A Comprehensive Review
Semin Liver Dis DOI: 10.1055/s-0040-1708806Noninvasive diagnostics for portal hypertension include imaging and functional tests, as well as blood-based biomarkers, and capture different features of the portal hypertensive syndrome. Definitive conclusions regarding their clinical utility require assessment of their diagnostic value in specific clinical settings (i.e., diagnosing a particular hemodynamic condition within a well-defined target population). Several noninvasive methods are predictive of clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥ 10 mm&thin...
Source: Seminars in Liver Disease - June 17, 2020 Category: Gastroenterology Authors: Mandorfer, Mattias Hern ández-Gea, Virginia Garc ía-Pagán, Juan Carlos Reiberger, Thomas Tags: Review Article Source Type: research

Donation after Circulatory Death: Potential Mechanisms of Injury and Preventative Strategies
Semin Liver Dis DOI: 10.1055/s-0040-1709487Donation after circulatory death (DCD) donors represent a potential means to help address the disparity between the number of patients awaiting liver transplantation (LT) and the availability of donor livers. While initial enthusiasm for DCD LT was high in the early 2000s, early reports of high rates of biliary complications and inferior graft survival resulted in reluctance among many transplant centers to use DCD liver grafts. As with all innovations in transplant practice, there is undoubtedly a learning curve associated with the optimal utilization of liver grafts from DCD don...
Source: Seminars in Liver Disease - June 17, 2020 Category: Gastroenterology Authors: Croome, Kristopher P. Tags: Review Article Source Type: research

Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials
We describe the different perfusion protocols, pitfalls in MP study design, and provide future perspectives. Recent trials in liver MP have revealed unique challenges beyond those seen in most clinical studies. Randomized trials, correct trial design, and interpretation of data are essential to generate the data necessary to prove if MP will be the new gold standard method of liver preservation. [...] 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 - June 17, 2020 Category: Gastroenterology Authors: Bonaccorsi-Riani, E. Br üggenwirth, I.M.A. Buchwald, J.E. Iesari, S. Martins, P.N. Tags: Review Article Source Type: research

Short Telomeres: Cause and Consequence in Liver Disease
Semin Liver Dis DOI: 10.1055/s-0040-1713007Short telomere syndrome is a genetically inherited syndrome resulting in premature telomere shortening. This premature shortening of telomeres can result in hematologic, pulmonary, vascular, gastrointestinal, and hepatic manifestations of disease. Identifying patients with short telomere syndrome can be a clinical challenge due to the multitude of potential manifestations and lack of widely available diagnostic tests. In this review, we will highlight hepatic manifestations of short telomere syndrome with a focus on diagnosis, testing, and potential treatments. [...] Thieme Medica...
Source: Seminars in Liver Disease - June 10, 2020 Category: Gastroenterology Authors: Penrice, Daniel D Simonetto, Douglas A Tags: Review Article Source Type: research

The NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis
Semin Liver Dis DOI: 10.1055/s-0040-1708540Nonalcoholic steatohepatitis (NASH) and alcoholic hepatitis (ASH) are advanced forms of fatty liver diseases that are associated with a high morbidity and mortality worldwide. Patients with ASH or NASH are more susceptible to the progression of fibrosis and cirrhosis up to the development of hepatocellular carcinoma. Currently, there are limited medical therapies available. Accompanied by the asymptomatic disease progression, the demand for liver transplants is high. This review provides an overview about the growing evidence for a central role of NLR family pyrin domain containin...
Source: Seminars in Liver Disease - June 10, 2020 Category: Gastroenterology Authors: Knorr, Jana Wree, Alexander Tacke, Frank Feldstein, Ariel E. Tags: Review Article Source Type: research

Nonalcoholic Steatohepatitis Promoting Kinases
Semin Liver Dis DOI: 10.1055/s-0040-1713115Nonalcoholic hepatitis (NASH) is the progressive inflammatory form of nonalcoholic fatty liver disease. Although the mechanisms of hepatic inflammation in NASH remain incompletely understood, emerging literature implicates the proinflammatory environment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. Interestingly, numerous NASH-promoting kinases in hepatocytes, immune cells, and adipocytes are activated by the lipotoxic insult associated with obesity. In the current review, we discuss recent advances in NASH-promoting kinases as disease mediators and thera...
Source: Seminars in Liver Disease - June 10, 2020 Category: Gastroenterology Authors: Ibrahim, Samar H. Hirsova, Petra Malhi, Harmeet Gores, Gregory J. Tags: Review Article Source Type: research

Hepatobiliary Differentiation: Principles from Embryonic Liver Development
Semin Liver Dis DOI: 10.1055/s-0040-1709679Hepatocytes and biliary epithelial cells (BECs), the two endodermal cell types of the liver, originate from progenitor cells called hepatoblasts. Based principally on in vitro data, hepatoblasts are thought to be bipotent stem cells with the potential to produce both hepatocytes and BECs. However, robust in vivo evidence for this model has only recently emerged. We examine the molecular mechanisms that stimulate hepatoblast differentiation into hepatocytes or BECs. In the absence of extrinsic cues, the default fate of hepatoblasts is hepatocyte differentiation. Inductive cues from...
Source: Seminars in Liver Disease - June 10, 2020 Category: Gastroenterology Authors: Freeburg, Scott H. Goessling, Wolfram Tags: Review Article Source Type: research

Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination
Semin Liver Dis DOI: 10.1055/s-0040-1708812Hepatitis C is a global public health threat. The introduction of direct-acting antivirals (DAAs) brings the prospect of curing the 71 million people living with the disease, dramatically changing the landscape of hepatitis C. The World Health Organization developed a roadmap for the elimination and cure of hepatitis C by 2030 with a clear goal with measurable targets. However, there is a lack of a well-defined strategy to tackle the hepatitis C virus (HCV) problem in children and adolescents vis-à-vis the adult population. Hepatitis C in children and adolescents can be add...
Source: Seminars in Liver Disease - June 10, 2020 Category: Gastroenterology Authors: El-Sayed, Manal H. Indolfi, Giuseppe Tags: Review Article Source Type: research

Noninvasive Tests in the Assessment of NASH and NAFLD Fibrosis: Now and Into the Future
Semin Liver Dis DOI: 10.1055/s-0040-1713006Noninvasive serum and imaging methods offer accessible, accurate, and safe assessment of fibrosis severity in nonalcoholic fatty liver disease. In contrast, current serum and imaging methods for the prediction of nonalcoholic steatohepatitis are not sufficiently accurate for routine clinical use. Serum fibrosis markers that incorporate direct measures of fibrogenesis (for example, hyaluronic acid) or fibrinolysis are generally more accurate than biomarkers not incorporating direct measures of fibrogenesis. Elastography methods are more accurate than serum markers for fibrosis asse...
Source: Seminars in Liver Disease - June 10, 2020 Category: Gastroenterology Authors: Adams, Leon A. Chan, Wah-Kheong Tags: Review Article Source Type: research

Hepatic Stellate Cell –Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis
Semin Liver Dis DOI: 10.1055/s-0040-1708876Chronic liver injury due to viral hepatitis, alcohol abuse, and metabolic disorders is a worldwide health concern. Insufficient treatment of chronic liver injury leads to fibrosis, causing liver dysfunction and carcinogenesis. Most cases of hepatocellular carcinoma (HCC) develop in the fibrotic liver. Pathological features of liver fibrosis include extracellular matrix (ECM) accumulation, mesenchymal cell activation, immune deregulation, and angiogenesis, all of which contribute to the precancerous environment, supporting tumor development. Among liver cells, hepatic stellate cell...
Source: Seminars in Liver Disease - April 1, 2020 Category: Gastroenterology Authors: Matsuda, Michitaka Seki, Ekihiro Tags: Review Article Source Type: research

Liver Matrix in Benign and Malignant Biliary Tract Disease
Semin Liver Dis DOI: 10.1055/s-0040-1705109The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and ...
Source: Seminars in Liver Disease - March 10, 2020 Category: Gastroenterology Authors: Fabris, Luca Cadamuro, Massimiliano Cagnin, Silvia Strazzabosco, Mario Gores, Gregory J. Tags: Review Article Source Type: research

Postsustained Virological Response Management in Hepatitis C Patients
Semin Liver Dis DOI: 10.1055/s-0040-1702944The introduction of direct-acting antiviral agents (DAA) has revolutionized management and care of patients with chronic hepatitis C virus (HCV) infection, leading to cure rates higher than 90% in patients with advanced liver disease as well. Viral eradication has been associated with longer survival, reduced mortality from both hepatic and extrahepatic causes, improvement in liver function, and reduced incidence of HCV-related extrahepatic diseases. While patients with mild fibrosis can safely be discharged after achievement of a sustained virological response, patients with adva...
Source: Seminars in Liver Disease - February 26, 2020 Category: Gastroenterology Authors: Masetti, Chiara Lleo, Ana Colombo, Matteo Colombo, Massimo Aghemo, Alessio Tags: Review Article Source Type: research

Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice
Semin Liver Dis DOI: 10.1055/s-0040-1701444Advancement in both bioengineering and cell biology of the liver led to the establishment of the first-generation humanized liver chimeric mouse (HLCM) model in 2001. The HLCM system was initially developed to satisfy the necessity for a convenient and physiologically representative small animal model for studies of hepatitis B virus and hepatitis C virus infection. Over the last two decades, the HLCM system has substantially evolved in quality, production capacity, and utility, thereby growing its versatility beyond the study of viral hepatitis. Hence, it has been increasingly em...
Source: Seminars in Liver Disease - February 18, 2020 Category: Gastroenterology Authors: Sugahara, Go Ishida, Yuji Sun, Jeffrey Tateno, Chise Saito, Takeshi Tags: Review Article Source Type: research

Drinking and Obesity: Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Interactions
Semin Liver Dis DOI: 10.1055/s-0040-1701443Alcohol and obesity are the main risk factors for alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD), respectively, and they frequently coexist. There are considerable synergistic interaction effects between hazardous alcohol use and obesity-associated metabolic abnormalities in the development and progression of fatty liver disease. Intermittent binge-drinking has been shown to promote steatohepatitis from obesity-related steatosis, and binge-drinking is associated with progression to cirrhosis even when average alcohol intake is within the currently used criter...
Source: Seminars in Liver Disease - February 17, 2020 Category: Gastroenterology Authors: Åberg, Fredrik F ärkkilä, Martti Tags: Review Article Source Type: research

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 6, 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 29, 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 29, 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 12, 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 5, 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 4, 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 14, 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 13, 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 13, 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 10, 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 10, 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 3, 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 17, 2019 Category: Gastroenterology Authors: Fickert, Peter Rosenkranz, Alexander R. Tags: Review Article Source Type: research