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 17, 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 9, 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 9, 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 4, 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 26, 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 28, 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 18, 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 18, 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 18, 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 11, 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 11, 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 11, 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 11, 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 11, 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 11, 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 2, 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 11, 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 27, 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 19, 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 18, 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 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