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 downs...
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 Hg; the threshold ...
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
