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Annals of the Academy of Medicine,... Nov 2023Non-alcoholic fatty liver disease (NAFLD) is known to be associated with metabolic syndrome of which diabetes is an important component. Although diabetes is a known...
INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) is known to be associated with metabolic syndrome of which diabetes is an important component. Although diabetes is a known risk factor for dementia, studies on the association between NAFLD and dementia still produce conflicting results. This study aimed to determine whether NAFLD would be a risk factor for the development of dementia in an elderly population.
METHOD
This study included 107,369 subjects aged ≥60 years in the Korean National Health Insurance Service-Senior cohort, entered in 2009 and followed up until 2015. NAFLD was diagnosed by calculating fatty liver index (FLI). Subjects were screened for dementia at baseline using a Korean Dementia Screening Questionnaire, and dementia was diagnosed using ICD-10 codes. Controls were randomly selected at a ratio of 1:5 from individuals who were at risk of becoming the case subjects at the time of selection.
RESULTS
From 107,369 subjects, 65,690 stroke- and dementia-free subjects without chronic hepatitis B or C or excessive alcohol drinking were selected for evaluation. Having NAFLD, determined by FLI, was associated with increased risk of dementia development (adjusted odds ratio [AOR] 1.493; 95% confidence interval [CI] 1.214-1.836). The increased risk of dementia in NAFLD subjects was independent of type 2 diabetes (AOR 1.421; 95% CI 1.013-1.994, in subjects with diabetes: AOR 1.540; 95% CI 1.179- 2.010, in subjects without diabetes).
CONCLUSION
In this population-based nested case-control study, having NAFLD increased the risk of dementia in elderly individuals, independent of accompanying diabetes.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Republic of Korea; Case-Control Studies; Dementia; Aged; Male; Female; Risk Factors; Middle Aged; Aged, 80 and over
PubMed: 38920146
DOI: 10.47102/annals-acadmedsg.202379 -
International Journal of Pharmaceutics Jun 2024Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of... (Review)
Review
Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of cirrhosis and hepatocellular carcinoma (HCC). This insidious condition stems from diverse factors such as obesity, genetic conditions, alcohol abuse, viral infections, autoimmune diseases, and toxic accumulation, manifesting as chronic liver diseases (CLDs) such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), viral hepatitis, drug-induced liver injury, and autoimmune hepatitis. Late detection of CLDs necessitates effective treatments to inhibit and potentially reverse disease progression. However, current therapies exhibit limitations in consistency and safety. A potential breakthrough lies in nanoparticle-based drug delivery strategies, offering targeted delivery to specific liver cell types, such as hepatocytes, Kupffer cells, and hepatic stellate cells. This review explores molecular targets for CLD treatment, ongoing clinical trials, recent advances in nanoparticle-based drug delivery, and the future outlook of this research field. Early intervention is crucial for chronic liver disease. Having a comprehensive understanding of current treatments, molecular biomarkers and novel nanoparticle-based drug delivery strategies can have enormous potential in guiding future strategies for the prevention and treatment of CLDs.
PubMed: 38917958
DOI: 10.1016/j.ijpharm.2024.124381 -
Cureus May 2024Legionnaires' disease is an atypical pneumonia caused by species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols....
Legionnaires' disease is an atypical pneumonia caused by species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols. Patients commonly present with fever, chills, and cough. However, in immunosuppressed patients or severe cases, the disease can lead to multiorgan failure. In recent years, the incidence of Legionnaires' disease has drastically increased and unfortunately is commonly underdiagnosed. Gold-standard diagnosis is made through sputum cultures; however, urine antigen remains the most common test used for diagnosis. Goal-directed care includes antibiotics and supportive care. This case highlights a rare and unique presentation of Legionnaires' disease presenting with an elevated 2:1 aspartate aminotransferase to alanine transaminase pattern, typically seen with alcoholic hepatitis.
PubMed: 38910759
DOI: 10.7759/cureus.60856 -
Journal of Zhejiang University.... Jun 2024Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated... (Review)
Review
Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated response element (ISRE) on the target gene and displays crucial roles in the interferon-induced signals and pathways. IRF-1, as an important medium, has all of the advantages of full cell cycle regulation, cell death signaling transduction, and reinforcing immune surveillance, which are well documented. Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases, including but not limited to inhibiting the replication of the hepatitis virus (A/B/C/E), alleviating the progression of liver fibrosis, and aggravating hepatic ischemia-reperfusion injury (HIRI). The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients, which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer; additionally, the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease (AFLD/NAFLD), cholangiocarcinoma suppression, and uncommon traits in other liver diseases that had previously received little attention. Intriguingly, several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal. In this paper, we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.
Topics: Interferon Regulatory Factor-1; Humans; Liver Diseases; Animals; Liver Neoplasms; Signal Transduction; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Reperfusion Injury; Cholangiocarcinoma
PubMed: 38910492
DOI: 10.1631/jzus.B2300159 -
Hepatology Communications Jul 2024The recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with the obesity epidemic in the United States. However, current mouse models do not...
BACKGROUND
The recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with the obesity epidemic in the United States. However, current mouse models do not fully replicate the combined insults of obesity, metabolic dysfunction-associated steatohepatitis, and alcohol. The aim of this study was to develop a new mouse model that recapitulates the robust inflammatory and fibrotic phenotype characteristic of human MetALD.
METHODS
Eight- to 10-week-old male C57BL/6 mice were fed chow or high fat-cholesterol-sugar diet (metabolic dysfunction-associated steatohepatitis diet) and in each group, some received alcohol in drinking water (ad libitum) and weekly alcohol binges (EtOH) for 3 months. The liver was assessed for features of AH.
RESULTS
MetALD mice displayed increased liver damage indicated by highly elevated ALT and bilirubin levels compared to all other groups. Liver steatosis was significantly greater in the MetALD mice compared to all other experimental groups. The inflammatory phenotype of MetALD was also recapitulated, including increased IL-6 and IL-1β protein levels as well as increased CD68+ macrophages and Ly6G+ neutrophils in the liver. Sirius red staining and expression of collagen 1, alpha-smooth muscle actin indicated advanced fibrosis in the livers of MetALD mice. In addition, indicators of epithelial-to-mesenchymal transition markers were increased in MetALD mice compared to all other groups. Furthermore, we found increased ductular reaction, dysregulated hedgehog signaling, and decreased liver synthetic functions, consistent with severe AH.
CONCLUSIONS
Alcohol administration in mice combined with metabolic dysfunction-associated steatohepatitis diet recapitulates key characteristics of human AH including liver damage, steatosis, robust systemic inflammation, and liver immune cell infiltration. This model results in advanced liver fibrosis, ductular reaction, decreased synthetic function, and hepatocyte dedifferentiation, suggesting a robust model of MetALD in mice.
Topics: Animals; Male; Mice; Disease Models, Animal; Mice, Inbred C57BL; Hepatitis, Alcoholic; Diet, High-Fat; Liver; Ethanol
PubMed: 38896082
DOI: 10.1097/HC9.0000000000000450 -
Clinical Science (London, England :... Jun 2024
PubMed: 38895778
DOI: 10.1042/CS-2010-0387_COR -
Biomedicine & Pharmacotherapy =... Jun 2024Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO)... (Review)
Review
Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease.
PubMed: 38878635
DOI: 10.1016/j.biopha.2024.116898 -
Annals of Hepato-biliary-pancreatic... Jun 2024Hepatic compartment syndrome (HCS) is a rare but life-threatening entity that consists of a decreased portal flow due to intraparenchymal hypertension secondary to... (Review)
Review
Hepatic compartment syndrome (HCS) is a rare but life-threatening entity that consists of a decreased portal flow due to intraparenchymal hypertension secondary to subcapsular liver hematoma. Lethal liver failure can be observed. We report three cases, and review the literature. A 54-year-old male was admitted for extensive hepatic subcapsular hematoma after blunt abdominal trauma. Initially, he underwent embolization of the hepatic artery's right branch, after which he presented clinical deterioration, major cytolysis (310 times the upper limit of normal [ULN]), and liver failure with a prothrombin time (PT) at 31.0%. A 56-year-old male underwent liver transplantation for acute alcoholic hepatitis. On postoperative day 2, he presented a hemorrhagic shock associated with deterioration of liver function (cytolysis 21 ULN, PT 39.0%) due to extensive hepatic subcapsular hematoma. A 59-year-old male presented a hepatic subcapsular hematoma five days after a cholecystectomy, revealed by abdominal pain with liver dysfunction (cytolysis 10 ULN, PT 63.0%). All patients ultimately underwent urgent surgery for liver capsule excision, hematoma evacuation, and liver packing, if needed. The international literature was screened for this entity. These three patients' outcomes were favorable, and all were alive at postoperative day 90. The literature review found 15 reported cases. HCS can occur after any direct or indirect liver trauma. Surgical decompression is the main treatment, and there is probably no place for arterial embolization, which may increase the risk of liver necrosis. A 13.3% mortality rate is reported. HCS is a rare complication of subcapsular liver hematoma that compresses the liver parenchyma, and leads to liver failure. Urgent surgical decompression is needed.
PubMed: 38867651
DOI: 10.14701/ahbps.24-040 -
Life Sciences Jun 2024The role of mast cells, traditionally recognized for their involvement in immediate hypersensitivity reactions, has garnered significant attention in liver diseases.... (Review)
Review
The role of mast cells, traditionally recognized for their involvement in immediate hypersensitivity reactions, has garnered significant attention in liver diseases. Studies have indicated a notable increase in mast cell counts following hepatic injury, underscoring their potential contribution to liver disorder pathogenesis. Predominantly situated in connective tissue that envelops the hepatic veins, bile ducts, and arteries, mast cells are central to both initiating and perpetuating liver disorders. Additionally, they are crucial for maintaining gastrointestinal barrier function. The gut-liver axis emphasizes the complex, two-way communication between the gut microbiome and the liver. Past research has implicated gut microbiota and their metabolites in the progression of hepatic disorders. This review sheds light on how mast cells are activated in various liver conditions such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, hepatic fibrogenesis, and hepatocellular carcinoma. It also briefly explores the connection between the gut microbiome and mast cell activation in these hepatic conditions.
PubMed: 38866220
DOI: 10.1016/j.lfs.2024.122818 -
Indian Journal of Gastroenterology :... Jun 2024Low-volume plasma exchange (PLEX) and low-dose steroid improve survival in severe alcoholic hepatitis. We aimed to compare one-year survival of very severe alcoholic...
BACKGROUND
Low-volume plasma exchange (PLEX) and low-dose steroid improve survival in severe alcoholic hepatitis. We aimed to compare one-year survival of very severe alcoholic hepatitis (VSAH) patients treated with centrifugal PLEX (cPLEX), membrane PLEX (mPLEX) or standard medical treatment (SMT).
METHODS
We retrospectively analyzed survival in consecutive VSAH patients treated at our department from November 2017 to September 2021. PLEX patients received low-volume PLEX along with low-dose steroid (tab. prednisolone 10 mg or 20 mg daily). To adjust for baseline differences between the three treatment (cPLEX, mPLEX or SMT) groups, propensity score (PS) matching was done. Acute-on-chronic liver failure (ACLF) was defined as per European Association for the Study of the Liver (EASL). The primary study outcome was one-year transplant-free survival of PS-matched VSAH patients treated with cPLEX compared to SMT.
RESULTS
Of 101 PLEX-eligible VSAH patients, 30 patients were treated with cPLEX, 21 with mPLEX and 50 with SMT. On comparing 30 PS-matched patients each in the cPLEX group vs. the SMT group, transplant-free survival in the cPLEX group was 86.7% at one month, 70% at three months and 52.4% at one year and in the SMT group was 33.3% at one month, 23.3% at three months and 16.7% at one year with hazard ratio (HR [95% CI]) in favor of the cPLEX group (0.29 [0.15-0.56], p < 0.001). Total 21 patients each (PS-matched) in cPLEX and mPLEX groups were compared and one-year survival was better with cPLEX (0.33 [0.16-0.69], p = 0.001). The sub-group analysis of VSAH (PS-matched cohort) patients with ACLF also showed better survival with cPLEX compared to SMT (0.38 [0.17-0.83], p = 0.003) and compared to mPLEX (0.43 [0.17-0.95], p = 0.03).
CONCLUSION
Better one-year transplant-free survival was noted among PS-matched VSAH patients treated with cPLEX (and low-dose steroid) compared to SMT (without steroid).
PubMed: 38848002
DOI: 10.1007/s12664-024-01569-3