Manuel Romero-Gómez, Juan Pablo Arab, Claudia P Oliveira, María Hernández, Marco Arrese, Helena Cortez-Pinto, Ramón Bataller
Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i...
April 4, 2024: Seminars in Liver Disease
Naoto Fujiwara, Genki Kimura, Hayato Nakagawa
The application of spatial transcriptomic technologies has significantly expanded our biological understanding. Hepatic intricate cellular heterogeneity and the pivotal role of zonation in maintaining hepatic function underscore how these technologies can unravel the complex spatial and cellular dynamics within both healthy and diseased livers. The article provides a comprehensive overview of the technical innovations and bioinformatics strategies that underpin spatial transcriptome analysis. Further, through recent discoveries in liver biology and pathology, enabled by these advanced methodologies, the review illustrates novel cell types, cell-cell interactions, and cellular reprograms in healthy and injured livers, as well as tumor microenvironment associated with patient prognosis and response to immune checkpoint inhibitors...
April 4, 2024: Seminars in Liver Disease
Clémence M Canivet, Jérôme Boursier, Rohit Loomba
In June 2023, under the patronage of the American Association for Study of Liver Disease, the European Association for Study of the Liver, and the Asociación Latinoamericana para el Estudio del Hígado with the involvement of 236 participants from around the world, a new nomenclature and definition for nonalcoholic fatty liver disease (NAFLD) has been proposed. Metabolic dysfunction-associated steatotic liver disease (MASLD) was defined as presence of hepatic steatosis and at least one of the cardiometabolic risk factors with alcohol intake less than 140 g/wk for women and 210 g/wk for men and no other causes of steatosis...
March 26, 2024: Seminars in Liver Disease
Takahiro Kodama, Tetsuo Takehara
This review examines the latest epidemiological and molecular pathogenic findings of metabolic-associated hepatocellular carcinoma (HCC). Its increasing prevalence is a significant concern and reflects the growing burden of obesity and metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. Metabolic-associated HCC has unique molecular abnormality and distinctive gene expression patterns implicating aberrations in bile acid, fatty acid metabolism, oxidative stress, and proinflammatory pathways...
March 18, 2024: Seminars in Liver Disease
Marialena Mouzaki, Jessica G Woo, Senad Divanovic
Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is common and can be seen as early as in utero . A growing body of literature suggests that gestational and early life exposures modify the risk of MASLD development in children. These include maternal risk factors, such as poor cardiometabolic health (e.g., obesity, gestational diabetes, rapid weight gain during pregnancy, and MASLD), as well as periconceptional dietary exposures, degree of physical activity, intestinal microbiome, and smoking...
February 29, 2024: Seminars in Liver Disease
Anna Tutusaus, Albert Morales, Pablo Garcia de Frutos, Montserrat Mari
TAM (TYRO3, AXL and MERTK) protein tyrosine kinase membrane receptors and their vitamin K-dependent ligands GAS6 and Protein S (PROS) are well-known players in tumor biology and autoimmune diseases. In contrast, TAM regulation of fibrogenesis and the inflammation mechanisms underlying metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis and, ultimately, liver cancer has recently been revealed. GAS6 and PROS binding to phosphatidylserine exposed in outer membranes of apoptotic cells links TAMs, particularly MERTK, with hepatocellular damage...
February 23, 2024: Seminars in Liver Disease
Mohamed El-Kassas, Abeer Awad, Mohamed Elbadry, Juan Pablo Arab
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is increasing globally, creating a growing public health concern. However, this disease is often not diagnosed, and accurate data on its epidemiology are limited in many geographical regions, making it challenging to provide proper care and implement effective national plans. To combat the increasing disease burden, screening and diagnosis must reach a significant number of high-risk subjects...
February 21, 2024: Seminars in Liver Disease
Fernando Bessone, Geraldine L Hillotte, Natalia Ahumada, Fernanda Jaureguizahar, Anabela C Medeot, Marcelo G Roma
Drug-induced liver injury (DILI) is an adverse reaction to medications and other xenobiotics that leads to liver dysfunction. Based on differential clinical patterns of injury, DILI is classified into hepatocellular, cholestatic, and mixed types; although hepatocellular DILI is associated with inflammation, necrosis, and apoptosis, cholestatic DILI is associated with bile plugs and bile duct paucity. Ursodeoxycholic acid (UDCA) has been empirically used as a supportive drug mainly in cholestatic DILI, but both curative and prophylactic beneficial effects have been observed for hepatocellular DILI as well, according to preliminary clinical studies...
February 20, 2024: Seminars in Liver Disease
Hao Liu, Vrishketan Sethi, Xingjie Li, Yao Xiao, Abhinav Humar
Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes...
February 12, 2024: Seminars in Liver Disease
Katrine Tholstrup Bech, Katrine Prier Lindvig, Maja Thiele, Laurent Castera
More than one-third of the adult world population has steatotic liver disease (SLD), with a few percent of individuals developing cirrhosis after decades of silent liver fibrosis accumulation. Lack of systematic early detection causes most patients to be diagnosed late, after decompensation, when treatment has limited effect and survival is poor. Unfortunately, no isolated screening test in primary care can sufficiently predict advanced fibrosis from SLD. Recent efforts, therefore, combine several parameters into screening algorithms, to increase diagnostic accuracy...
January 23, 2024: Seminars in Liver Disease
MohammadMahdi Saeidinejad, Ahmed Elshabrawi, Supachaya Sriphoosanaphan, Fausto Andreola, Gautam Mehta, Banwari Agarwal, Rajiv Jalan
Acute-on-chronic liver failure (ACLF), a clinical syndrome that can develop at any stage in the progression of cirrhotic liver disease, is characterized by an acute decompensation in liver function with associated multiorgan failure and high short-term mortality. Current evidence points to ACLF being reversible, particularly in those at the lower end of the severity spectrum. However, there are no specific treatments for ACLF, and overall outcomes remain poor. Expedited liver transplantation as a treatment option is limited by organ shortage and a lack of priority allocation for this indication...
November 2023: Seminars in Liver Disease
Cathrin L C Gudd, Roosey Sheth, Mark R Thursz, Evangelos Triantafyllou, Lucia A Possamai
In recent years cancer treatment has been revolutionized by the development and wide application of checkpoint inhibitor (CPI) drugs, which are a form of immunotherapy. CPI treatment is associated with immune-related adverse events, off-target tissue destructive inflammatory complications, which may affect a range of organs, with liver inflammation (hepatitis) being one of the more commonly noted events. This is a novel form of drug-induced liver injury and a rapidly evolving field, as our understanding of both the basic immunopathology of CPI hepatitis (CPI-H) and optimal clinical management, races to catch up with the increasing application of this form of immunotherapy in clinical practice...
November 2023: Seminars in Liver Disease
Oluwashanu Balogun, Kari Nejak-Bowen
The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess porphyrins, and porphyria-associated hepatic dysfunction ranges from minor abnormalities to liver failure. In this review, the first of a three-part series, we describe the defects commonly found in each of the eight enzymes involved in heme biosynthesis...
November 2023: Seminars in Liver Disease
Sierra R Wilson, Andrew W Duncan
The liver's unique chromosomal variations, including polyploidy and aneuploidy, influence hepatocyte identity and function. Among the most well-studied mammalian polyploid cells, hepatocytes exhibit a dynamic interplay between diploid and polyploid states. The ploidy state is dynamic as hepatocytes move through the "ploidy conveyor," undergoing ploidy reversal and re-polyploidization during proliferation. Both diploid and polyploid hepatocytes actively contribute to proliferation, with diploids demonstrating an enhanced proliferative capacity...
November 2023: Seminars in Liver Disease
Fátima Manzano-Núñez, Lara Prates Tiago Aguilar, Christine Sempoux, Frédéric P Lemaigre
Biliary tract cancer is a devastating malignancy of the bile ducts and gallbladder with a dismal prognosis. The study of precancerous lesions has received considerable attention and led to a histopathological classification which, in some respects, remains an evolving field. Consequently, increasing efforts have been devoted to characterizing the molecular pathogenesis of the precursor lesions, with the aim of better understanding the mechanisms of tumor progression, and with the ultimate goal of meeting the challenges of early diagnosis and treatment...
November 2023: Seminars in Liver Disease
Xinpu Han, Qianhui Sun, Manman Xu, Guanghui Zhu, Ruike Gao, Baoyi Ni, Jie Li
Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively utilized, substantial hurdles have arisen for clinicians. These include countering ICIs resistance and ensuring precise efficacy assessments of these drugs, especially in the context of hepatocellular carcinoma (HCC). This review attempts to offer a holistic overview of the latest insights into the ICIs resistance mechanisms in HCC, the molecular underpinnings, and immune response...
November 2023: Seminars in Liver Disease
Rajesh Kumar Dutta, JiHye Jun, Kuo Du, Anna Mae Diehl
The purpose of this review is to summarize current knowledge about the role of the Hedgehog signaling pathway in liver homeostasis and disease. Hedgehog is a morphogenic signaling pathway that is active in development. In most healthy tissues, pathway activity is restricted to stem cell and/or stromal cell compartments, where it enables stem cell self-renewal and tissue homeostasis. Aberrant over-activation of Hedgehog signaling occurs in many cancers, including hepatocellular and cholangio- carcinoma. The pathway is also activated transiently in stromal cells of injured tissues and orchestrates normal wound healing responses, including inflammation, vascular remodeling and fibrogenesis...
October 6, 2023: Seminars in Liver Disease
Joseph Dempsey, George Ioannou, Rotonya Carr
The steatotic diseases of non-alcoholic fatty liver disease, alcohol-associated liver disease and chronic Hepatitis C account for the majority of liver disease prevalence, morbidity and mortality worldwide. While these diseases have distinct pathogenic and clinical features, dysregulated lipid droplet (LD) organelle biology represents a convergence of pathogenesis in all three. With increasing understanding of hepatocyte LD biology, we now understand the roles of LD proteins involved in these diseases but also how genetics modulate LD biology to either exacerbate or protect against the phenotypes associated with steatotic liver diseases...
October 5, 2023: Seminars in Liver Disease
Kshitij Deshmukh, Udayan Apte
Exposure to hepatotoxic chemicals is involved in liver disease-related morbidity and mortality worldwide. The liver responds to damage by triggering compensatory hepatic regeneration. Physical agent or chemical-induced liver damage disrupts hepatocyte proteostasis, including endoplasmic reticulum (ER) homeostasis. Post-liver injury ER experiences a homeostatic imbalance, followed by active ER stress response signaling. Activated ER stress response causes selective upregulation of stress response genes and downregulation of many hepatocyte genes...
August 18, 2023: Seminars in Liver Disease
Dominick J Hellen, Saul J Karpen
No abstract text is available yet for this article.
August 2023: Seminars in Liver Disease
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