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Acta Pharmaceutica Sinica. B Mar 2024Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated... (Review)
Review
Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases. However, current treatment options are limited, highlighting the urgent need for the development of new therapies. As a reversible regulatory mechanism, epigenetic modification is implicated in many biological processes, including liver fibrosis. Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases, although the current evidence is still controversial. This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications, including DNA methylation, histone modification, and RNA modification, in liver fibrotic diseases. The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted. Finally, available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed. In summary, elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.
PubMed: 38486982
DOI: 10.1016/j.apsb.2023.10.023 -
Journal of Family Medicine and Primary... Jan 2024Globally, liver diseases accounts for 4% of all deaths. Annually, over 2 million deaths occur due to preventable causes of chronic liver diseases and liver cancer like... (Review)
Review
Globally, liver diseases accounts for 4% of all deaths. Annually, over 2 million deaths occur due to preventable causes of chronic liver diseases and liver cancer like fatty liver diseases (alcoholic or non alcoholic) and viral hepatitis B and C. The burden of chronic liver diseases are increasing, and the epidemiology and demographics of people affected by these diseases are changing. Policy changes, vaccination, screening, lifestyle changes and public health awareness is the key to curb down liver disaeses. To achieve the ultimate goal of reducing mortality and linkage to care for those who need specialized care for liver disease, it is vital to have dedicated preventive hepatology clinics in sync with existing liver or gastroenterology clinics at tertary care level.
PubMed: 38482317
DOI: 10.4103/jfmpc.jfmpc_1536_23 -
Cureus Feb 2024Alcoholic hepatitis (AH) is a clinicopathologic illness caused by excessive alcohol abuse and is a precursor of cirrhosis. The leukemoid reaction (LR) is characterized...
Alcoholic hepatitis (AH) is a clinicopathologic illness caused by excessive alcohol abuse and is a precursor of cirrhosis. The leukemoid reaction (LR) is characterized by a strikingly raised granulocyte count of 40,000-50,000 cells/mm. The LR usually suggests an acute inflammatory reaction. It is usually mistaken for chronic myeloid leukemia. The initial phase of leukocytosis occurs due to the releasing of cells from the bone marrow with more immature cells, causing a left upper shift in the ratio of immature to mature neutrophils and macrophages. The LR is usually seen in cases of leukemia but is rare to present in alcohol hepatitis. Excessive alcohol use causes AH in persons with or without underlying chronic liver disease. In severe AH, leukemoid responses have been associated with very poor prognosis and short-term mortality. We describe a case of a 35-year-old male with severe AH with an LR.
PubMed: 38481914
DOI: 10.7759/cureus.54039 -
Redox Biology May 2024Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver...
Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23. Animals were fed with an alcohol-containing liquid diet alone or in combination with ERRγ inverse agonist. FGF23 is mainly expressed in hepatocytes in the human liver, and it is upregulated in ALD patients. In mice, chronic alcohol feeding leads to liver damage and induced FGF23 in liver, but not in other organs. FGF23 is transcriptionally regulated by ERRγ in response to alcohol-mediated activation of the CB1R. Alcohol induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost in ERRγ-LKO mice, and an inverse agonist mediated inhibition of ERRγ transactivation significantly improved alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23 dependent. In line, FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress. We recognized CBIR-ERRγ-FGF23 axis in facilitating ALD pathology through hepatic CYP2E1 induction. Thus, we propose FGF23 as a potential therapeutic target to treat ALD.
Topics: Animals; Humans; Mice; Cytochrome P-450 CYP2E1; Drug Inverse Agonism; Ethanol; Hepatocytes; Liver; Liver Diseases, Alcoholic; Oxidative Stress
PubMed: 38479224
DOI: 10.1016/j.redox.2024.103107 -
Biomedicine & Pharmacotherapy =... Apr 2024Metabolic dysfunction-associated steatotic liver disease(MASLD), formerly known as non-alcoholic fatty liver disease(NAFLD), has become a major cause of chronic liver... (Review)
Review
Metabolic dysfunction-associated steatotic liver disease(MASLD), formerly known as non-alcoholic fatty liver disease(NAFLD), has become a major cause of chronic liver disease and a significant risk factor for hepatocellular carcinoma, which poses a huge burden on global public health and economy. MASLD includes steatotic liver disease, steatohepatitis, and cirrhosis, and the latter two cause great harm to human health and life, even complicated with liver cancer. Immunologic mechanism plays a major role in promoting its development into hepatitis and cirrhosis. Now more and more evidences show that T cells play an important role in the progression of MASLD. In this review, we discuss the double roles of T cells in MASLD from the perspective of T cell response pathways, as well as new evidences regarding the possible application of immunomodulatory therapy in MASH.
Topics: Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Immunomodulation; Immunity
PubMed: 38479177
DOI: 10.1016/j.biopha.2024.116333 -
Nutrients Feb 2024Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis,... (Review)
Review
Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice. In this review, we highlight the results of the most recent evidence on this controversial topic, in order to understand the effect of mild alcohol use in this category of individuals. The quantification of alcohol intake, the composition of the tested populations, and the discrepancy between different works in relation to the outcomes represent important limitations emerging from the scientific literature. In patients with NAFLD, a beneficial effect is demonstrated only in a few works. Even if there is limited evidence in patients affected by chronic viral hepatitis, a clear deleterious effect of drinking in determining disease progression in a dose-dependent manner emerges. Poor data are available about more uncommon pathologies such as hemochromatosis. Overall, based on available data, it is not possible to establish a safe threshold for alcohol intake in patients with liver disease.
Topics: Humans; Disease Progression; Non-alcoholic Fatty Liver Disease; Ethanol; Alcohol Drinking
PubMed: 38474740
DOI: 10.3390/nu16050613 -
Diagnostics (Basel, Switzerland) Feb 2024Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of... (Review)
Review
Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.
PubMed: 38472961
DOI: 10.3390/diagnostics14050490 -
United European Gastroenterology Journal Mar 2024Alcohol-related liver disease (ALD) represents the most common indication for liver transplantation (LT) worldwide. Outcomes of LT for ALD are comparable with those of... (Review)
Review
Alcohol-related liver disease (ALD) represents the most common indication for liver transplantation (LT) worldwide. Outcomes of LT for ALD are comparable with those of LT for other etiologies; however, ALD is still considered a controversial indication for LT, mainly because it is considered a self-inflicted disease with a high risk of return to alcohol use after LT. Pre-LT evaluation criteria have changed over time, with a progressive re-evaluation of the required pre-transplant duration of abstinence. Despite the fact that some transplant programs still require 6 months of abstinence in order to consider a patient suitable for LT, there is increasing evidence that a pre-transplant abstinence period of <6 months can be considered for well-selected patients. Early LT for severe alcohol-related hepatitis that has not responded to medical therapy has been shown to be an effective therapeutic option with high survival benefit when performed within strict and well-recognized criteria. However, high variability in LT access exists for these patients due to the presence of social and medical stigma. A psycho-social assessment, together with an evaluation by an addiction specialist, should be mandatory in patients with ALD who are potential candidates for LT in order to assess the risk of post-transplant return to alcohol use and to ensure good long-term outcomes. Finally, before LT, attention should be paid to the presence of other potential comorbidities (i.e., cardiovascular and neurological diseases), which could represent a potential contraindication to LT. Similarly, after LT, patients should be adequately monitored for the development of cardiovascular events and screened for "de novo" tumors, although standardized protocols for this monitoring do not exist at this time.
Topics: Humans; Liver Transplantation; Liver Diseases, Alcoholic; Alcohol Abstinence; Recurrence; Alcohol Drinking; Hepatitis, Alcoholic
PubMed: 38456339
DOI: 10.1002/ueg2.12548 -
Heliyon Mar 2024Lately, liver diseases were categorized as one of the most prevalent health problems globally as it causes a severe threat to mankind all over the world due to the wide... (Review)
Review
Lately, liver diseases were categorized as one of the most prevalent health problems globally as it causes a severe threat to mankind all over the world due to the wide range of occurrence. There are multiple factors causing hepatic disorders, such as alcohol, virus, poisons, adverse effects of drugs, poor diet, inherited conditions and obesity. Liver diseases have various types including alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, liver cancer, hepatocellular carcinoma, liver fibrosis and hepatic inflammation. Therefore, it is imperative to find effective and efficacious agents in managing liver diseases. , an endophytic fungus and containing many bioactive compounds, could be served as a forked medication for enormous number and types of maladies. It was characterized by producing biochemical compounds which had rare pharmacological properties as it may be found in a limit number of other medicinal plants. The majority of the past researches related to recited the fungal negative field either on the pathogenic effects of the fungus on economical crops or on the fungal chemical components to know how to resist it. The present review will highlight on the bright side of and introduce the functional activities of its chemical compounds for treating its target diseases. The key point of illustrated studies in this article is displaying wide range of detected bioactive compounds isolated from and in other illustrated studies it was elucidated the therapeutical and pharmacological potency of these biologically active compounds (isolated from medicinal plants sources) against different types of liver diseases including non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and others. It was demonstrated that contains unique types of isoflavones, flavonoids, phenols and another active chemical compounds, and these compounds showed recently a fabulous clinical contribution in the therapy of liver injury diseases, which opens new and unprecedented way for evaluating the maintaining efficacy of bioactive compounds in dealing with hepatic complications and its remedy impacting on liver diseases and injured hepatocytes through recommending implement a practical study.
PubMed: 38455549
DOI: 10.1016/j.heliyon.2024.e26562 -
Hepatology Communications Mar 2024Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain the...
BACKGROUND
Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain the mainstay of drug therapy. However, ~40% of patients do not respond to this treatment, and the mechanisms underlying the altered response to corticosteroids are not understood. The current study aimed to identify changes in hepatic protein expression associated with responsiveness to corticosteroids and prognosis in patients with AH.
METHODS
Patients with AH were enrolled based on the National Institute on Alcohol Abuse and Alcoholism inclusion criteria for acute AH and further confirmed by a diagnostic liver biopsy. Proteomic analysis was conducted on liver samples acquired from patients with AH grouped as nonresponders (AH-NR, n = 7) and responders (AH-R, n = 14) to corticosteroids, and nonalcohol-associated liver disease controls (n = 10). The definition of responders was based on the clinical prognostic model, the Lille Score, where a score < 0.45 classified patients as AH-R and a score > 0.45 as AH-NR. Primary outcomes used to assess steroid response were Lille Score (eg, improved liver function) and survival at 24 weeks.
RESULTS
Reduced levels of the glucocorticoid receptor and its transcriptional co-activator, glucocorticoid modulatory element-binding protein 2, were observed in the hepatic proteome of AH-NR versus AH-R. The corticosteroid metabolizing enzyme, 11-beta-hydroxysteroid dehydrogenase 1, was increased in AH-NR versus AH-R along with elevated mitochondrial DNA repair enzymes, while several proteins of the heat shock pathway were reduced. Analysis of differentially expressed proteins in AH-NR who survived 24 weeks relative to AH-NR nonsurvivors revealed several protein expression changes, including increased levels of acute phase proteins, elevated coagulation factors, and reduced mast cell markers.
CONCLUSIONS
This study identified hepatic proteomic changes that may predict responsiveness to corticosteroids and mortality in patients with AH.
Topics: Humans; Heat-Shock Proteins; Glucocorticoids; Proteomics; Steroids; Hepatitis, Alcoholic; Liver Diseases, Alcoholic
PubMed: 38437061
DOI: 10.1097/HC9.0000000000000393