The Receptor Interacting Protein Kinases in the Liver
Semin Liver Dis 2018; 38: 073-086 DOI: 10.1055/s-0038-1629924The receptor interacting serine/threonine kinase1 and 3 (RIPK1, RIPK3) are regulators of cell death and survival. RIPK1 kinase activity is required for necroptosis and apoptosis, while its scaffolding function is necessary for survival. Although both proteins can mediate apoptosis, RIPK1 and RIPK3 are most well-known for their role in the execution of necroptosis via the mixed lineage domain like pseudokinase. Necroptosis is a caspase-independent regulated cell death program which was first described in cultured cells with unknown physiologic relevance in the liv...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Dara, Lily Tags: Review Article Source Type: research
Targeting Hepatitis D
Semin Liver Dis 2018; 38: 066-072 DOI: 10.1055/s-0037-1621711New therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into cells through the inhibition of the sodium taurocholate cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation of the large HD antigen, required for virion assembly; (3) the presumed reduction by the nuclei...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Rizzetto, Mario Tags: Review Article Source Type: research
Mucosal-Associated Invariant T Cells in Chronic Inflammatory Liver Disease
Semin Liver Dis 2018; 38: 060-065 DOI: 10.1055/s-0037-1621709The broadening field of microbiome research has led to a substantial reappraisal of the gut–liver axis and its role in chronic liver disease. The liver is a central immunologic organ that is continuously exposed to food and microbial-derived antigens from the gastrointestinal tract. Mucosal-associated invariant T (MAIT) cells are enriched in the human liver and can be activated by inflammatory cytokines and microbial antigens. In chronic inflammatory liver disease, MAIT cells are depleted suggesting an impaired MAIT cell-dependent protection against bacterial i...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Bolte, Fabian J. Rehermann, Barbara Tags: Review Article Source Type: research
Fibrolamellar Carcinoma: Recent Advances and Unresolved Questions on the Molecular Mechanisms
Semin Liver Dis 2018; 38: 051-059 DOI: 10.1055/s-0037-1621710Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that affects adolescents and young adults without underlying liver disease. Surgery remains the mainstay of therapy; however, most patients are either not surgical candidates or suffer from recurrence. There is no approved systemic therapy and the overall survival remains poor. Historically classified as a subtype of hepatocellular carcinoma (HCC), FLC has a unique clinical, histological, and molecular presentation. At the genomic level, FLC contains a single 400kB deletion in chr...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Lalazar, Gadi Simon, Sanford M. Tags: Review Article Source Type: research
Genetic and Epigenetic Heterogeneity in Normal Liver Homeostasis and Its Implications for Liver Disease and Hepatocellular Cancer
Semin Liver Dis 2018; 38: 041-050 DOI: 10.1055/s-0037-1621712Hepatocellular carcinoma (HCC) is the most prevalent primary tumor of the liver, and is steadily becoming one of the most lethal cancers worldwide. Liver resection, which is the recommended procedure for early localized HCC, results in frequent recurrence (50–70%), while the standard of care for late-stage HCC, multikinase inhibitors, only improves survival by a few months. The lack of success for these treatment modalities is attributable, at least in part, to marked phenotypic heterogeneity within the tumor. Intratumoral heterogeneity (ITH) has emerged as a d...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Hlady, Ryan A. Robertson, Keith D. Tags: Review Article Source Type: research
Hepatic Damage by Natural Remedies
Semin Liver Dis 2018; 38: 021-040 DOI: 10.1055/s-0038-1623518The rising burden of herbal and dietary supplement hepatotoxicity (HILI) is a growing concern in Western countries. The estimated incidence of HILI in well-designed prospective studies ranges from less than 1 to 3 individuals per 100,000 inhabitants/year. Herbal hepatotoxicity has a particular signature encompassing female predominance, hepatocellular type of damage with markedly elevated transaminases on presentation, more common unintentional rechallenge, and a greater risk of death/liver transplantation. Herbal hepatotoxicity recognition is particularly challe...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Andrade, Raul J. Medina-Caliz, Inmaculada Gonzalez-Jimenez, Andres Garcia-Cortes, Miren Lucena, M. Isabel Tags: Review Article Source Type: research
Can Elastography Differentiate Isolated Fatty Liver from Nonalcoholic Steatohepatitis?
Semin Liver Dis 2018; 38: 014-020 DOI: 10.1055/s-0037-1618587Ultrasound and magnetic resonance (MR)-based elastography have demonstrated excellent performance for noninvasive staging of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD); however, their ability to differentiate isolated fatty liver from nonalcoholic steatohepatitis (NASH) is unclear. In this review, the authors provide background on elastography and review the ability of elastography to discriminate between isolated steatosis and NASH. Studies with available data on the diagnosis of NASH histology are limited to vibration-controlled transien...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Ajmera, Veeral Loomba, Rohit Tags: Review Article Source Type: research
Nonalcoholic Fatty Liver Disease in Children
Semin Liver Dis 2018; 38: 001-013 DOI: 10.1055/s-0038-1627456Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children who present with particular risk factors including obesity, sedentary lifestyle, and/or a predisposing genetic background. The worldwide prevalence of NAFLD in children is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. To date, the etiopathogenesis of primary NAFLD in children is unknown. Understanding the pathogenetic...
Source: Seminars in Liver Disease - February 22, 2018 Category: Gastroenterology Authors: Mann, Jake P. Valenti, Luca Scorletti, Eleonora Byrne, Christopher D. Nobili, Valerio Tags: Review Article Source Type: research
Systematic Review and Meta-Analysis: Prevalence of Small Intestinal Bacterial Overgrowth in Chronic Liver Disease
Semin Liver Dis 2017; 37: 388-400 DOI: 10.1055/s-0037-1608832The authors conducted a meta-analysis of the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with chronic liver disease (CLD) and controls. Using the search terms “small intestinal bacterial overgrowth (SIBO)” and “chronic liver disease (CLD)” or “cirrhosis,” 19 case-control studies were identified. Utilizing breath tests, the prevalence of SIBO in CLD was 35.80% (95% CI, 32.60–39.10) compared with 8.0% (95% CI, 5.70–11.00) in controls. Using culture techniques, the prevalence was 68.31% (95% CI, 59.62–76.00) in CLD patien...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Shah, Ayesha Shanahan, Erin Macdonald, Graeme A. Fletcher, Linda Ghasemi, Pegah Morrison, Mark Jones, Mike Holtmann, Gerald Tags: Review Article Source Type: research
Liver Sinusoidal Endothelial Cell: An Update
Semin Liver Dis 2017; 37: 377-387 DOI: 10.1055/s-0037-1617455This update focuses on two main topics. First, recent developments in our understanding of liver sinusoidal endothelial cell (LSEC) function will be reviewed, specifically elimination of blood-borne waste, immunological function of LSECs, interaction of LSECs with liver metastases, LSECs and liver regeneration, and LSECs and hepatic fibrosis. Second, given the current emphasis on rigor and transparency in biomedical research, the update discusses the need for standardization of methods to demonstrate identity and purity of isolated LSECs, pitfalls in methods that...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: DeLeve, Laurie D. Maretti-Mira, Ana C. Tags: Review Article Source Type: research
Multifunctional YY1 in Liver Diseases
Semin Liver Dis 2017; 37: 363-376 DOI: 10.1055/s-0037-1607451The transcription factor Yin Yang 1 (YY1) is a multifunctional protein that can activate or repress gene expression, depending on the cellular context. While YY1 is ubiquitously expressed and highly conserved between species, its role varies among the diverse cell types and includes proliferation, differentiation, and apoptosis. Upregulated YY1 expression is found in pathogenic conditions, such as human hepatocellular carcinoma and hepatitis B virus infection, and its roles in the molecular pathogenic mechanisms in liver (i.e., fibrosis, carcinogenesis, viral-ind...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Zhang, Mengjie Zhang, Yi Yang, Shuang Zhou, Jian Gao, Weiwu Yang, Xia Yang, Di Tian, Zhiqiang Wu, Yuzhang Ni, Bing Tags: Review Article Source Type: research
Salvage Therapies for Autoimmune Hepatitis: A Critical Review
Semin Liver Dis 2017; 37: 343-362 DOI: 10.1055/s-0037-1607453Several salvage therapies have been identified for autoimmune hepatitis refractory or recalcitrant to conventional therapy; however, the optimal salvage strategy remains unclear. High-dose prednisolone is currently recommended as the front-line salvage therapy, with alternative immunosuppressive therapies reserved for continuing treatment failure. Of the second-line therapies, the calcineurin inhibitors, cyclosporine and tacrolimus, and mycophenolate mofetil are preferred and have the most accrued clinical data. However, none of these have undergone rigorous clin...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Roberts, Stuart K. Kemp, William Tags: Review Article Source Type: research
Clinical Trial Design for Alcoholic Hepatitis
Semin Liver Dis 2017; 37: 332-342 DOI: 10.1055/s-0037-1608788Alcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months, treatment options are limited and ineffective. Recent advances on the understanding of the pathomechanisms of AH have identified numerous potential targets for new therapeutic interventions. Many of those targets are currently under preclinical testing and/or in human clinical trials for nonalcoholic steatohepatitis. Thus, the field of AH should be ready to launch new efforts and targeted clinical trial...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Szabo, Gyongyi Tags: Review Article Source Type: research
The Microbiome in Primary Sclerosing Cholangitis: Current Evidence and Potential Concepts
Semin Liver Dis 2017; 37: 314-331 DOI: 10.1055/s-0037-1608801The close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease has inspired hypothetical models in which gut bacteria or bacterial products are key players in PSC pathogenesis. Several studies using high-throughput sequencing technology to characterize the gut microbiota in PSC have been published over the past years. They all report reduced diversity and significant shifts in the overall composition of the gut microbiota. However, it remains unclear as to whether the observed changes are primary or secondary to PSC development...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Hov, Johannes R. Karlsen, Tom H. Tags: Review Article Source Type: research
Timing, Management, and Outcomes of Liver Transplantation in Primary Sclerosing Cholangitis
Semin Liver Dis 2017; 37: 305-313 DOI: 10.1055/s-0037-1608655Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease that often progresses to secondary biliary cirrhosis and end-stage liver disease. Short of liver transplantation (LT), there is no effective treatment for PSC. PSC accounts for approximately 5% of total adult LTs in the US and is currently the fifth most common indication for LT. Patient and graft survival for PSC is among the highest for all indications for LT. The main factors that impact outcomes after LT for PSC include biliary strictures, rejection, and recurrence of...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Martin, Eric F. Levy, Cynthia Tags: Review Article Source Type: research
