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Stem Cells (Dayton, Ohio) Aug 2023The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for... (Review)
Review
The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant strides have been made in exploring their biological activity. Clinical application of MSC has shifted the paradigm from using their regenerative potential to one which harnesses their immunomodulatory properties. Reassuringly, MSCs have been extensively investigated for over 30 years with encouraging efficacy and safety data from translational and early phase clinical studies, but questions remain about their utility. Therefore, in this review, we examine the translational and clinical studies using MSCs in various liver diseases and their impact on dampening immune-mediated liver damage. Our key observations include progress made thus far with use of MSCs for clinical use, inconsistency in the literature to allow meaningful comparison between different studies and need for standardized protocols for MSC manufacture and administration. In addition, the emerging role of MSC-derived extracellular vesicles as an alternative to MSC has been reviewed. We have also highlighted some of the remaining clinical challenges that should be addressed before MSC can progress to be considered as therapy for patients with liver disease.
Topics: Humans; Liver Diseases; Liver Transplantation; Cell- and Tissue-Based Therapy; Immunomodulation; Mesenchymal Stem Cells; Extracellular Vesicles; Mesenchymal Stem Cell Transplantation
PubMed: 37052348
DOI: 10.1093/stmcls/sxad029 -
Journal of Medical Systems Jul 2023Medical image analysis plays a pivotal role in the evaluation of diseases, including screening, surveillance, diagnosis, and prognosis. Liver is one of the major organs... (Review)
Review
Medical image analysis plays a pivotal role in the evaluation of diseases, including screening, surveillance, diagnosis, and prognosis. Liver is one of the major organs responsible for key functions of metabolism, protein and hormone synthesis, detoxification, and waste excretion. Patients with advanced liver disease and Hepatocellular Carcinoma (HCC) are often asymptomatic in the early stages; however delays in diagnosis and treatment can lead to increased rates of decompensated liver diseases, late-stage HCC, morbidity and mortality. Ultrasound (US) is commonly used imaging modality for diagnosis of chronic liver diseases that includes fibrosis, cirrhosis and portal hypertension. In this paper, we first provide an overview of various diagnostic methods for stages of liver diseases and discuss the role of Computer-Aided Diagnosis (CAD) systems in diagnosing liver diseases. Second, we review the utility of machine learning and deep learning approaches as diagnostic tools. Finally, we present the limitations of existing studies and outline future directions to further improve diagnostic accuracy, as well as reduce cost and subjectivity, while also improving workflow for the clinicians.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Cirrhosis; Diagnosis, Computer-Assisted
PubMed: 37432493
DOI: 10.1007/s10916-023-01968-7 -
Nature Communications Dec 2023Hepatic steatosis is the result of imbalanced nutrient delivery and metabolism in the liver and is the first hallmark of Metabolic dysfunction-associated steatotic liver...
Hepatic steatosis is the result of imbalanced nutrient delivery and metabolism in the liver and is the first hallmark of Metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is the most common chronic liver disease and involves the accumulation of excess lipids in hepatocytes, inflammation, and cancer. Mitochondria play central roles in liver metabolism yet the specific mitochondrial functions causally linked to MASLD remain unclear. Here, we identify Mitochondrial Fission Process 1 protein (MTFP1) as a key regulator of mitochondrial and metabolic activity in the liver. Deletion of Mtfp1 in hepatocytes is physiologically benign in mice yet leads to the upregulation of oxidative phosphorylation (OXPHOS) activity and mitochondrial respiration, independently of mitochondrial biogenesis. Consequently, liver-specific knockout mice are protected against high fat diet-induced steatosis and metabolic dysregulation. Additionally, Mtfp1 deletion inhibits mitochondrial permeability transition pore opening in hepatocytes, conferring protection against apoptotic liver damage in vivo and ex vivo. Our work uncovers additional functions of MTFP1 in the liver, positioning this gene as an unexpected regulator of OXPHOS and a therapeutic candidate for MASLD.
Topics: Animals; Mice; Fatty Liver; Liver; Liver Diseases; Mice, Knockout; Mitochondria; Mitochondria, Liver
PubMed: 38123539
DOI: 10.1038/s41467-023-44143-9 -
World Journal of Gastroenterology Mar 2024Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine... (Review)
Review
Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.
Topics: Humans; Blood Glucose Self-Monitoring; Sarcopenia; Blood Glucose; Liver Cirrhosis; Endocrine System; Diabetes Mellitus; Insulin; Hypoglycemia
PubMed: 38577191
DOI: 10.3748/wjg.v30.i9.1073 -
Ugeskrift For Laeger May 2024This review investigates that, in 2023, fatty liver disease underwent a name change to "steatotic liver disease" (SLD). SLD now includes metabolic dysfunction-associated... (Review)
Review
This review investigates that, in 2023, fatty liver disease underwent a name change to "steatotic liver disease" (SLD). SLD now includes metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), and metabolic and alcohol-related liver disease (MetALD). The renaming aims to better incorporate alcohol intake and metabolic risk factors into disease classification and to diminish the stigma associated with the previous nomenclature. Early identification of the patient's aetiology is important for the prognosis which can be improved by interventions against the causative risk factors.
Topics: Humans; Terminology as Topic; Risk Factors; Fatty Liver; Fatty Liver, Alcoholic; Alcohol Drinking; Non-alcoholic Fatty Liver Disease; Liver Diseases, Alcoholic
PubMed: 38808766
DOI: 10.61409/V12230778 -
Clinical and Molecular Hepatology Jul 2023Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with... (Review)
Review
Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.
Topics: Humans; Organoids; Liver Diseases; Cell Differentiation
PubMed: 36880210
DOI: 10.3350/cmh.2022.0428 -
Current Hypertension Reports Aug 2023Metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver that occurs in the majority of patients in combination with metabolic... (Review)
Review
PURPOSE OF REVIEW
Metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver that occurs in the majority of patients in combination with metabolic dysfunction in the form of overweight or obesity. In this review, we highlight the cardiovascular complications in MAFLD patients as well as some potential mechanisms linking MAFLD to the development of cardiovascular disease and highlight potential therapeutic approaches to treating cardiovascular diseases in patients with MAFLD.
RECENT FINDINGS
MAFLD is associated with an increased risk of cardiovascular diseases (CVD), including hypertension, atherosclerosis, cardiomyopathies, and chronic kidney disease. While clinical data have demonstrated the link between MAFLD and the increased risk of CVD development, the mechanisms responsible for this increased risk remain unknown. MAFLD can contribute to CVD through several mechanisms including its association with obesity and diabetes, increased levels of inflammation, and oxidative stress, as well as alterations in hepatic metabolites and hepatokines. Therapies to potentially treat MAFLD-induced include statins and lipid-lowering drugs, glucose-lowering agents, antihypertensive drugs, and antioxidant therapy.
Topics: Humans; Cardiovascular Diseases; Hypertension; Oxidative Stress; Obesity; Liver Diseases; Non-alcoholic Fatty Liver Disease
PubMed: 37191842
DOI: 10.1007/s11906-023-01242-8 -
International Immunopharmacology Aug 2023COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries,... (Review)
Review
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Pandemics; Post-Acute COVID-19 Syndrome; Liver Diseases
PubMed: 37315370
DOI: 10.1016/j.intimp.2023.110439 -
Frontiers in Immunology 2024Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic steatohepatitis (NASH). It is characterized by... (Review)
Review
Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic steatohepatitis (NASH). It is characterized by inflammation and injury of the liver in the presence of cardiometabolic risk factors and may eventually result in the development of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Several pathogenic mechanisms are involved in the transition from MASH to HCC, encompassing metabolic injury, inflammation, immune dysregulation and fibrosis. In this context, Gas6 (Growth Arrest-Specific 6) and TAM (Tyro3, Axl, and MerTK) receptors may play important roles. The Gas6/TAM family is involved in the modulation of inflammation, lipid metabolism, fibrosis, tumor progression and metastasis, processes which play an important role in the pathophysiology of acute and chronic liver diseases. In this review, we discuss MASH-associated HCC and the potential involvement of the Gas6/TAM system in disease development and progression. In addition, since therapeutic strategies for MASH and HCC are limited, we also speculate regarding possible future treatments involving the targeting of Gas6 or TAM receptors.
Topics: Humans; Carcinoma, Hepatocellular; Proto-Oncogene Proteins; Liver Neoplasms; Inflammation; Fibrosis; Fatty Liver
PubMed: 38298195
DOI: 10.3389/fimmu.2024.1332818 -
Annals of Hepatology 2023Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, the disease has not received sufficient... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, the disease has not received sufficient attention compared to the associated diseases such as diabetes mellitus and obesity. In 2020 it was proposed to rename NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in order to recognize the metabolic risk factors and the complex pathophysiological mechanisms associated with its development. Furthermore, along with the implementation of the proposed diagnostic criteria, the aim is to address the whole clinical spectrum of the disease, regardless of BMI and the presence of other hepatic comorbidities. As would it be expected with such a paradigm shift, differing viewpoints have emerged regarding the benefits and disadvantages of renaming fatty liver disease. The following review aims to describe the way to the MAFLD from a historical, pathophysiological and clinical perspective in order to highlight why MAFLD is the approach to follow.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 37468095
DOI: 10.1016/j.aohep.2023.101138