Overdiagnosis: An Understudied Issue in Hepatocellular Carcinoma Surveillance
Semin Liver Dis 2017; 37: 296-304 DOI: 10.1055/s-0037-1608775Overdiagnosis, the detection of clinically insignificant disease that would not otherwise impact the patient's lifespan, is a phenomenon that has been described in several solid tumors, such as prostate, breast, thyroid, and lung cancers. Population-based efforts to reduce hepatocellular carcinoma (HCC) mortality in cirrhosis patients by screening and early detection may result in the overdiagnosis of HCC. One of the harms of overdiagnosis is subsequent overtreatment, which can result in increased costs, as well as physical side effects, psychological harms, and ...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Rich, Nicole E. Parikh, Neehar D. Singal, Amit G. Tags: Review Article Source Type: research
HCC Risk Scores: Useful or Not?
Semin Liver Dis 2017; 37: 287-295 DOI: 10.1055/s-0037-1607452The advent and efficacy of surveillance for hepatocellular carcinoma (HCC) has necessitated the refinement of assessing who is at risk for this cancer. Initially, risk was assessed for all individuals with hepatitis B and all those with cirrhosis. However, the majority of these individuals do not develop HCC so that providing surveillance for all is a waste of resources. There are now many different scores that have been developed that allow better identification of who is at risk and who is not. Specific models have been developed for hepatitis B before and on t...
Source: Seminars in Liver Disease - December 22, 2017 Category: Gastroenterology Authors: Sherman, Morris Tags: Review Article Source Type: research
Is Propensity Score Analysis a Valid Surrogate of Randomization for the Avoidance of Allocation Bias?
Semin Liver Dis 2017; 37: 275-286 DOI: 10.1055/s-0037-1606213Randomized clinical trials are the gold standard when experimental designs are feasible. Randomization allows the handling of allocation bias for known and unknown confounders. Specific tools such as blocking, stratification, and dynamic allocation provide additional guarantees to simple randomization. When an experimental design is not feasible, the propensity score (PS) has been shown to produce greater benefit than traditional methods (i.e., restriction, stratification, matching and adjusting). There appears to be a hierarchy in terms of the effectiveness of b...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Torres, Ferran R íos, José Saez-Pe ñataro, Joaquín Pontes, Caridad Tags: Review Article Source Type: research
Functional Imaging and Assessment of Antitumor Activity in Systemic Therapy for Hepatocellular Carcinoma
Semin Liver Dis 2017; 37: 259-274 DOI: 10.1055/s-0037-1606254Increasing use of novel systemic treatment options in the management of patients with advanced hepatocellular carcinoma (HCC) such as antiangiogenic and molecular-targeted therapies, poses unique challenges for effective treatment monitoring and efficacy assessment. The traditional morphological criteria such as response evaluation criteria in solid tumor (RECIST) rely on changes in tumor size to determine treatment efficacy. However, these criteria based on tumor morphology may not be suitable to monitor response to newer targeted therapies as early functional c...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Kambadakone, Avinash Baliyan, Vinit Zhu, Andrew X. Tags: Review Article Source Type: research
Quantitative Imaging in Diffuse Liver Diseases
Semin Liver Dis 2017; 37: 243-258 DOI: 10.1055/s-0037-1603651Cross-sectional imaging methods and more specifically ultrasonography and magnetic resonance imaging (MRI), have increasing roles in the quantitative evaluation of diffuse liver diseases. Particularly, ultrasound elastography is becoming the standard first-line examination for diagnosing severe liver fibrosis. Quantitative ultrasonography also brings information for staging portal hypertension in compensated cirrhosis and for grading liver steatosis. Quantitative MRI offers a multiparametric approach to assess the severity of liver steatosis, iron overload, fibro...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Van Beers, Bernard E. Garteiser, Philippe Leporq, Benjamin Rautou, Pierre-Emmanuel Valla, Dominique Tags: Review Article Source Type: research
Challenges to a Cure for HBV Infection
Semin Liver Dis 2017; 37: 231-242 DOI: 10.1055/s-0037-1606212Current first-choice treatments for chronic hepatitis B are able to efficiently induce viral suppression in the majority of patients, but life-long therapy is needed to maintain infection under control due to their inability to eliminate the virus from infected hepatocytes. The residual viral replication and antigen production in most patients under treatment substantially contributes to the residual risk of hepatocarcinogenesis. New therapeutic approaches are needed to overcome hepatitis B virus persistence in the infected cells, or at least to control its trans...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Testoni, Barbara Levrero, Massimo Zoulim, Fabien Tags: Review Article Source Type: research
Epigenetics in Liver Fibrosis
Semin Liver Dis 2017; 37: 219-230 DOI: 10.1055/s-0037-1605371Liver fibrosis is a common consequence of chronic liver injury and is a key determinant of liver-associated morbidity and mortality. Identification of new mechanisms of fibrosis, including disease-specific molecular drivers, remains relevant to reveal novel biomarkers and therapeutic targets. Recently, greater accessibility to more advanced molecular methods that can assess changes in epigenetic regulation has stimulated more research investigating the epigenetic landscape of liver fibrosis. Such studies have revealed changes in DNA methylation, histone acetylati...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Massey, Veronica Cabezas, Joaquin Bataller, Ramon Tags: Review Article Source Type: research
Learning the Roles of the Hepatic Adaptive Immune System in Hepatocellular Carcinoma —Nature's Guide for Successful Cancer Immunotherapy
Semin Liver Dis 2017; 37: 210-218 DOI: 10.1055/s-0037-1606255The different roles of the adaptive immune system in cancer are beginning to unfold. The dramatic responses to immune check point drugs in some tumors generated an accelerated need for understanding the complex set of interactions between tumor and immune cells. In view of the major pathophysiological role of immune cells in hepatocellular carcinoma, it is not surprising that malignant hepatocytes interact extensively with adaptive immune cells, resulting in both protumor immunopathology and antitumor protective immunity. Identifying potential responders to drugs...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Heikenw älder, Mathias Pikarsky, Eli Tags: Review Article Source Type: research
Natural Killer Cells in Liver Disease
Semin Liver Dis 2017; 37: 198-209 DOI: 10.1055/s-0037-1603946Natural killer (NK) cells comprise one of the most abundant immune cell populations in human liver and the nature and functions of these cells have been a focus of recent interest. Here, we consider the possible roles of NK cells in diverse liver diseases, concentrating on data from patient studies. NK cells can be protective, killing virally infected and cancerous cells in the liver and limiting fibrosis by eliminating hepatic stellate cells. However, they can also be deleterious, contributing to pathology in viral hepatitis by killing hepatocytes and downregula...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Male, Victoria Stegmann, Kerstin A. Easom, Nicholas J. Maini, Mala K. Tags: Review Article Source Type: research
Macrophages in Nonalcoholic Fatty Liver Disease: A Role Model of Pathogenic Immunometabolism
Semin Liver Dis 2017; 37: 189-197 DOI: 10.1055/s-0037-1604480Nonalcoholic fatty liver disease (NAFLD) and its progressive inflammatory form, nonalcoholic steatohepatitis (NASH), are leading causes of liver cirrhosis and hepatocellular carcinoma. Metabolism and inflammation are intimately interrelated in NAFLD/NASH, as expressed by the term immunometabolism. Hepatic macrophages mediate inflammatory responses during metabolic disorders and can stimulate or dismantle liver fibrosis. Their functional diversity is partly explained by heterogeneous macrophage subsets: tissue-resident Kupffer cells and monocyte-derived macrophage...
Source: Seminars in Liver Disease - August 28, 2017 Category: Gastroenterology Authors: Krenkel, Oliver Tacke, Frank Tags: Review Article Source Type: research
Disorders in Hepatic Copper Secretion: Wilson's Disease and Pleomorphic Syndromes
Semin Liver Dis 2017; 37: 175-188 DOI: 10.1055/s-0037-1602764Wilson's disease (WD) is a rare disease the prevalence of which is higher than previously thought. Caused by genetic variations that target the copper (Cu) transporting P-ATPase Atp7b and disrupt the elimination of Cu by the liver, Atp7b truncations are associated with early severe liver disease and missense mutations with the late presentation of neurologic disorders. The asymptomatic initiation and false unimportance of initial symptoms often delays the crucial early diagnosis and a treatment that is lifesaving. The occasional acute liver failure persistently t...
Source: Seminars in Liver Disease - May 31, 2017 Category: Gastroenterology Authors: Lalioti, Vasiliki Tsubota, Akihito Sandoval, Ignacio V. Tags: Review Article Source Type: research
Epigenetics in the Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Semin Liver Dis 2017; 37: 159-174 DOI: 10.1055/s-0037-1603324Epigenomics, the study of modifications to genetic material that do not alter the underlying DNA sequence, is generating increasing interest as a means to help clarify disease pathogenesis and outcomes. Although genome-wide association studies have identified several potential candidate genes that may be implicated in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), it is estimated that these genes explain less than 20% of the heritability of these diseases. Thus, to date, the origins of “missing heritability” for PBC and PSC remain...
Source: Seminars in Liver Disease - May 31, 2017 Category: Gastroenterology Authors: Cheung, Angela C. LaRusso, Nicholas F. Gores, Gregory J. Lazaridis, Konstantinos N. Tags: Review Article Source Type: research
Emerging Concepts and Human Trials in Alpha-1-Antitrypsin Deficiency Liver Disease
Semin Liver Dis 2017; 37: 152-158 DOI: 10.1055/s-0037-1602586In α-1-antitrypsin (AAT) deficiency, individuals homozygous for the AAT mutant Z gene synthesize large quantities of mutant Z protein in the liver, which folds improperly during biogenesis and is retained within the hepatocytes rather than appropriated secreted. This accumulation of mutant Z protein triggers an intracellular injury cascade causing cell death in the population of hepatocytes with the largest accumulations of Z protein. Hepatocellular proliferation, hepatic fibrosis, and hepatocellular cancer in some individuals can be the result. New insights fro...
Source: Seminars in Liver Disease - May 31, 2017 Category: Gastroenterology Authors: Teckman, Jeffrey H. Tags: Review Article Source Type: research
Update on the Mechanisms of Liver Regeneration
Semin Liver Dis 2017; 37: 141-151 DOI: 10.1055/s-0037-1601351Liver possesses many critical functions such as synthesis, detoxification, and metabolism. It continually receives nutrient-rich blood from gut, which incidentally is also toxin-rich. That may be why liver is uniquely bestowed with a capacity to regenerate. A commonly studied procedure to understand the cellular and molecular basis of liver regeneration is that of surgical resection. Removal of two-thirds of the liver in rodents or patients instigates alterations in hepatic homeostasis, which are sensed by the deficient organ to drive the restoration process. Alt...
Source: Seminars in Liver Disease - May 31, 2017 Category: Gastroenterology Authors: Preziosi, Morgan E. Monga, Satdarshan P. Tags: Review Article Source Type: research
The Human Gut Microbiome in Liver Diseases
Semin Liver Dis 2017; 37: 128-140 DOI: 10.1055/s-0037-1602763Recent advances in culture-independent laboratory techniques and bioinformatics have contributed to enriched characterizations of the gut microbiota and microbiome in chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, primary biliary cholangitis, and cirrhosis. In this review, the authors focus on studies characterizing and modulating the gut microbiota and microbiome in humans. The majority of studies that characterized microbiota involved a small number of patients using 16S ribosomal RNA ge...
Source: Seminars in Liver Disease - May 31, 2017 Category: Gastroenterology Authors: Davis, Brian C. Bajaj, Jasmohan S. Tags: Review Article Source Type: research
