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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 -
Journal of Hepatology Jul 2020The exclusion of other chronic liver diseases including "excess" alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated... (Review)
Review
The exclusion of other chronic liver diseases including "excess" alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, "positive criteria" to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward.
Topics: Causality; Consensus; Diabetes Mellitus, Type 2; Disease Progression; Fatty Liver; Humans; Liver Cirrhosis; Metabolic Diseases; Obesity; Terminology as Topic
PubMed: 32278004
DOI: 10.1016/j.jhep.2020.03.039 -
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 -
Cell May 2021Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Its more advanced subtype, nonalcoholic steatohepatitis (NASH), connotes... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Its more advanced subtype, nonalcoholic steatohepatitis (NASH), connotes progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. Here we provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of NAFLD, the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in NASH.
Topics: Carcinoma, Hepatocellular; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 33989548
DOI: 10.1016/j.cell.2021.04.015 -
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 -
Cellular & Molecular Immunology Jan 2021The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ... (Review)
Review
The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota. The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens. Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases. Of immense importance is the step from high-throughput sequencing (correlation) to mechanistic studies (causality) and therapeutic intervention. Here, we review the gut microbiota, liver immunology, and the interaction between the gut and liver. In addition, the impairment in the gut-liver axis found in various liver diseases is reviewed here, with an emphasis on alcohol-associated liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and autoimmune liver disease (AILD). On the basis of growing evidence from these preclinical studies, we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.
Topics: Animals; Gastrointestinal Microbiome; Humans; Liver; Liver Diseases
PubMed: 33318628
DOI: 10.1038/s41423-020-00592-6 -
Cells Mar 2020The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is... (Review)
Review
The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver's physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.
Topics: Animals; Humans; Liver; Liver Diseases; Mitochondria; Mitophagy; Receptors, Cell Surface; Signal Transduction
PubMed: 32244304
DOI: 10.3390/cells9040837 -
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 -
Current Gastroenterology Reports Sep 2020Non-cirrhotic portal hypertension (NCPH) includes a heterogeneous group of conditions. The aim of this paper is to make an overview on the denominations, diagnostical... (Review)
Review
PURPOSE OF THE REVIEW
Non-cirrhotic portal hypertension (NCPH) includes a heterogeneous group of conditions. The aim of this paper is to make an overview on the denominations, diagnostical features and management of porto-sinusoidal vascular disease (PSVD) and chronic portal vein thrombosis (PVT) being the main causes of NCPH in the Western world.
RECENT FINDINGS
The management of NCPH consists in the treatment of associated diseases and of portal hypertension (PH). PH due to PSVD or PVT is managed similarly to PH due to cirrhosis. TIPS placement and liver transplantation are considerable options in patients with refractory variceal bleeding/ascites and with progressive liver failure. Anticoagulation is a cornerstone both in the treatment of thrombosis in PSVD and in the prevention of thrombosis recurrence in patients with portal cavernoma. Physicians should be aware of the existence of PSVD and chronic PVT and actively search them in particular settings. To now, the management of portal hypertension-related complications in NCPH is the same of those of cirrhosis. Large cooperative studies on the natural history of NCPH are necessary to better define its management.
Topics: Chronic Disease; Disease Progression; Humans; Hypertension, Portal; Liver; Liver Cirrhosis; Liver Diseases; Portal Vein; Vascular Diseases
PubMed: 32940785
DOI: 10.1007/s11894-020-00792-0 -
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