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Clinical and Molecular Hepatology Feb 2023"Metabolic dysfunction-associated fatty liver disease (MAFLD)" is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation.... (Review)
Review
"Metabolic dysfunction-associated fatty liver disease (MAFLD)" is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Metabolic Diseases
PubMed: 36443926
DOI: 10.3350/cmh.2022.0367 -
Nature Reviews. Gastroenterology &... Oct 2019Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C,... (Review)
Review
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.
Topics: Carcinoma, Hepatocellular; Global Health; Humans; Liver Neoplasms; Risk Factors
PubMed: 31439937
DOI: 10.1038/s41575-019-0186-y -
Molecular Aspects of Medicine Dec 2021The liver is a highly dynamic metabolic organ that plays critical roles in plasma protein synthesis, gluconeogenesis and glycogen storage, cholesterol metabolism and... (Review)
Review
The liver is a highly dynamic metabolic organ that plays critical roles in plasma protein synthesis, gluconeogenesis and glycogen storage, cholesterol metabolism and bile acid synthesis as well as drug/xenobiotic metabolism and detoxification. Research from the past decades indicate that autophagy, the cellular catabolic process mediated by lysosomes, plays an important role in maintaining cellular and metabolic homeostasis in the liver. Hepatic autophagy fluctuates with hormonal cues and the availability of nutrients that respond to fed and fasting states as well as circadian activities. Dysfunction of autophagy in liver parenchymal and non-parenchymal cells can lead to various liver diseases including non-alcoholic fatty liver diseases, alcohol associated liver disease, drug-induced liver injury, cholestasis, viral hepatitis and hepatocellular carcinoma. Therefore, targeting autophagy may be a potential strategy for treating these various liver diseases. In this review, we will discuss the current progress on the understanding of autophagy in liver physiology. We will also discuss several forms of selective autophagy in the liver and the molecular signaling pathways in regulating autophagy of different cell types and their implications in various liver diseases.
Topics: Autophagy; Humans; Lipid Metabolism; Liver; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 34120768
DOI: 10.1016/j.mam.2021.100973 -
Advances in Clinical and Experimental... Apr 2018Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a... (Review)
Review
Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.
Topics: Critical Illness; Humans; Intensive Care Units; Liver; Liver Failure; Sepsis; Shock, Septic
PubMed: 29558045
DOI: 10.17219/acem/68363 -
Annual Review of Pathology Jan 2023Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related... (Review)
Review
Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis of ALD. We also summarize current understanding of innate immune responses, liver sinusoidal endothelial cell dysfunction and hepatic stellate cell activation, and gut-liver and adipose-liver cross talk in response to ethanol. In addition,we describe the current potential therapeutic targets and clinical trials aimed at alleviating hepatocyte injury, reducing inflammatory responses, and targeting gut microbiota, for the treatment of ALD.
Topics: Humans; Liver Diseases, Alcoholic; Liver; Ethanol; Hepatocytes; Fibrosis
PubMed: 36270295
DOI: 10.1146/annurev-pathmechdis-031521-030435 -
Gastroenterology Sep 2020Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial,... (Review)
Review
Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora.
Topics: Animals; Bacterial Translocation; Disease Models, Animal; Dysbiosis; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Liver; Liver Diseases; Permeability
PubMed: 32569766
DOI: 10.1053/j.gastro.2020.04.077 -
The Korean Journal of Gastroenterology... Apr 2020Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. During sepsis, the liver has essential roles, such as... (Review)
Review
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. During sepsis, the liver has essential roles, such as immune defense and metabolic adaptation to inflammation. In addition, it is a target for sepsis-related injury, including hypoxic hepatitis, cholestasis, drug-induced liver injury, and secondary sclerosing cholangitis in critically ill patients. In particular, the mortality rate due to sepsis is four times higher in patients with cirrhosis, warranting a high index of suspicion for infection, appropriate diagnosis, and prompt antimicrobial treatment. The most recent definition of sepsis (Sepsis-3) no longer uses systemic inflammatory response syndrome (SIRS) and is based on the signs of organ dysfunction, which can be assessed by the Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores. The qSOFA score can be applied at the bedside before any tests and is believed to be suggestive of sepsis when at least two of the following criteria are met: altered consciousness, respiratory rate ≥22/min, and systolic blood pressure ≤100 mmHg. While the qSOFA score performs well in the general population, its role in cirrhotic patients is unclear. This paper briefly reviews the current knowledge of the pathogenesis, definition of sepsis, and sepsis-related liver dysfunction. Furthermore, this review summarizes the clinical applicability of Sepsis-3 in cirrhotic patients.
Topics: Cholangitis, Sclerosing; Cholestasis; Cytokines; Humans; Liver; Liver Cirrhosis; Liver Diseases; Sepsis
PubMed: 32326684
DOI: 10.4166/kjg.2020.75.4.182 -
Molecules (Basel, Switzerland) Jan 2017Silymarin is the extract of , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver... (Review)
Review
Silymarin is the extract of , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Chronic Disease; Humans; Liver Diseases; Silybin; Silymarin
PubMed: 28125040
DOI: 10.3390/molecules22020191 -
Cells Sep 2019Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and... (Review)
Review
Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.
Topics: Animals; Hepatectomy; Humans; Inflammasomes; Inflammation; Inflammation Mediators; Liver; Liver Diseases; Liver Transplantation; Postoperative Complications; Reperfusion Injury
PubMed: 31547621
DOI: 10.3390/cells8101131 -
The Journal of Clinical Investigation Feb 2024Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple... (Review)
Review
Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple steatosis, steatohepatitis, cirrhosis, and superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field of ALD over the last 20 years, the pathogenesis of ALD remains obscure, and there are currently no FDA-approved drugs for the treatment of ALD. In this Review, we discuss new insights into the pathogenesis and therapeutic targets of ALD, utilizing the study of multiomics and other cutting-edge approaches. The potential translation of these studies into clinical practice and therapy is deliberated. We also discuss preclinical models of ALD, interplay of ALD and metabolic dysfunction, alcohol-associated liver cancer, the heterogeneity of ALD, and some potential translational research prospects for ALD.
Topics: Humans; Liver Diseases, Alcoholic; Ethanol; Fatty Liver; Liver Cirrhosis; Carcinoma, Hepatocellular; Liver Neoplasms; Liver
PubMed: 38299591
DOI: 10.1172/JCI176345