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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 -
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 -
Medicine Jun 2024In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic... (Observational Study)
Observational Study
In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic steatohepatitis (NASH) and liver fibrosis. The observation and control groups comprised 133 patients with CHB complicated by NASH and 50 healthy patients from our hospital, respectively. Liver function indices, including alanine aminotransferase, glutamic aminotransferase, γ-glutamyltransferase, total bilirubin, total protein, and total cholesterol, were determined using an automatic biochemical analyzer. Hyaluronic acid, type III procollagen, type IV collagen, laminin, and CK18-M65 and M30 levels were detected using ELISA. Serum CK18-M65 and M30 levels in patients with CHB complicated by NASH were positively correlated with the liver fibrosis stage (P < .05). While serum CK18-M65 demonstrated a low diagnostic value for liver fibrosis in the S0-1 stage, it exhibited good diagnostic value for S2-3 stage liver fibrosis. Serum CK18-M30 displayed good diagnostic value for S0-1 and S2-3 hepatic fibrosis, particularly for S2-3 hepatic fibrosis. Elevated serum CK18-M65 and CK18-M30 levels in patients with CHB complicated with NASH suggest their potential utility in evaluating the progression of liver fibrosis in this population. In particular, CK18-M30 exhibits superior diagnostic efficiency.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Hepatitis B, Chronic; Male; Female; Keratin-18; Liver Cirrhosis; Adult; Middle Aged; Biomarkers; Peptide Fragments; Liver Function Tests; Case-Control Studies; Clinical Relevance
PubMed: 38847670
DOI: 10.1097/MD.0000000000038342 -
Indian Journal of Pathology &... Jun 2024Serum immunoglobulin G (IgG) level is elevated in autoimmune liver diseases (AILDs), especially autoimmune hepatitis (AIH). However, its utility is limited in current...
BACKGROUND
Serum immunoglobulin G (IgG) level is elevated in autoimmune liver diseases (AILDs), especially autoimmune hepatitis (AIH). However, its utility is limited in current practice as different criteria propose different cut-off values leading to considerable ambiguity.
MATERIALS AND METHODS
A cross-sectional study was conducted among patients with AILD who underwent a liver biopsy over a ten-year period. From 17644 liver biopsies, 630 patients were included and divided into three groups-AIH (455 patients), primary biliary cholangitis (PBC) (97 patients), and overlap (78 patients). Clinical and laboratory details were collected and histological findings were reviewed. Non-cirrhotic non-alcoholic steatohepatitis (NASH) cases were taken as the control group for IgG level comparison.
RESULTS
Among AIH patients, IgG values of >2 times the upper limit of normal (ULN) were associated with significant elevation of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, and necroinflammatory activity. IgG level of >1.1 times ULN lacks specificity in differentiating AIH from the control group. The receiver operating characteristic (ROC) curve demonstrates maximum sensitivity and specificity at a cut-off value of >1.3 times ULN.
CONCLUSION
Serum IgG cut-off value for diagnosing AIH, either in isolation or as a component of overlap syndrome, needs revision and uniformity. IgG value of >2 times ULN in AIH is associated with severe AIH. A new cut-off value of >1.3 times ULN is proposed.
PubMed: 38847214
DOI: 10.4103/ijpm.ijpm_865_23 -
Nature Communications Jun 2024Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing...
Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.
Topics: Non-alcoholic Fatty Liver Disease; Animals; Basic Helix-Loop-Helix Transcription Factors; Male; Macrophages; Humans; Mice; Mice, Knockout; Sphingosine; Liver; Mice, Inbred C57BL; Aryl Hydrocarbon Receptor Nuclear Translocator; Liver Cirrhosis; Disease Models, Animal
PubMed: 38834568
DOI: 10.1038/s41467-024-48954-2 -
Biomedicine & Pharmacotherapy =... Jul 2024Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases,... (Review)
Review
Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases, etc., and is closely related to the progression of liver disease. Currently, the mechanisms of liver fibrosis and its treatment are hot research topics in the field of liver disease remedy. Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential, which can ameliorate fibrosis through hepatic-directed differentiation, paracrine effects, and immunomodulation. However, the low inner-liver colonization rate, low survival rate, and short duration of intervention after stem cell transplantation have limited their wide clinical application. With the intensive research on liver fibrosis worldwide, it has been found that MSCs and MSCs-derived exosomes combined with drugs have shown better intervention efficiency than utilization of MSCs alone in many animal models of liver fibrosis. In this paper, we review the interventional effects and mechanisms of mesenchymal stem cells and their exosomes combined with drugs to alleviate hepatic fibrosis in vivo in animal models in recent years, which will provide new ideas to improve the efficacy of mesenchymal stem cells and their exosomes in treating hepatic fibrosis in the clinic.
Topics: Exosomes; Mesenchymal Stem Cells; Humans; Animals; Liver Cirrhosis; Mesenchymal Stem Cell Transplantation
PubMed: 38834005
DOI: 10.1016/j.biopha.2024.116848 -
European Journal of Gastroenterology &... Jul 2024Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components...
Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 million inhabitants) between 2009 and 2019 were collected from patients with AIH, PBC, PSC, or toxic liver disease at the time of diagnosis. MAFLD was diagnosed as macrovesicular steatosis ≥5% together with obesity, type-2 diabetes, or signs of metabolic dysregulation. Of 648 patients included, steatosis was observed in 15.6% (n = 101), of which 94.1% (n = 95) was due to MAFLD. Prevalence of coexisting MAFLD in the four liver diseases varied between 12.4 and 18.2% (P = 0.483). Fibrosis was more severe in MAFLD among patients with toxic liver disease (P = 0.01). Histopathological characteristics otherwise showed similar distribution among MAFLD and non-FLD controls. Alcohol consumption was higher in MAFLD group among patients with AIH or PBC (P < 0.05 for both). In AIH, smoking was more common in patients with coexisting MAFLD (P = 0.034). Prevalence of coexisting MAFLD in other primary liver diseases is lower than reported in general population. Histopathology of MAFLD patients did not clearly differ from non-FLD ones. Alcohol and smoking were associated with MAFLD in AIH.
Topics: Humans; Male; Female; Middle Aged; Hepatitis, Autoimmune; Prevalence; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Adult; Finland; Aged; Chemical and Drug Induced Liver Injury; Fatty Liver; Non-alcoholic Fatty Liver Disease; Obesity; Metabolic Syndrome; Biopsy; Diabetes Mellitus, Type 2; Retrospective Studies; Risk Factors
PubMed: 38829946
DOI: 10.1097/MEG.0000000000002785 -
Journal of Family Medicine and Primary... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is an escalating global health issue. Early detection and precise diagnosis are imperative for effective management.
CONTEXT
Non-alcoholic fatty liver disease (NAFLD) is an escalating global health issue. Early detection and precise diagnosis are imperative for effective management.
AIM
To evaluate the sociodemographic and clinical attributes of study participants concerning their ultrasound grading with FibroScan and FLI values.
SETTINGS AND DESIGN
A cross-sectional study was carried out among patients visiting gastroenterology clinics at a tertiary care hospital situated in Karachi, Pakistan.
METHODS AND MATERIAL
We included participants after written informed consent underwent an extensive array of laboratory assessments, encompassing liver function tests, lipid profile, fasting blood sugar analysis, hepatitis B and C screening, and abdominal ultrasound, while those with positive hepatitis B or C markers, documented alcohol use, or those who declined to offer informed consent were excluded from the study.
STATISTICAL ANALYSIS
Data were analyzed using SPSS version 26.
RESULTS
Around 225 patients were studied with a median age of 42 years (IQR = 34-50 years). Metabolic syndrome (MetS) was present in 61.8%. Steatosis was not found among 4.9% of patients, whereas severe steatosis was seen among 51.1% of patients. Significant variations in BMI, WC, GGT, and TG levels were identified when comparing FLI scores. The same was observed for the frequency of MetS as FLI scores increased. The agreement between FLI and ultrasound observations was found to be slight (k = 0.077, = 0.027). On the multivariable regression model, having diabetes, elevated serum glutamate pyruvate transaminase levels and mild disease on ultrasound were associated with increased odds of severe steatosis.
CONCLUSION
FLI is a good predictor of frequency of MetS and NAFLD and correlates well with increasing steatosis score (CAP) on FibroScan which can be utilized for early detection of NAFLD in primary care.
PubMed: 38827715
DOI: 10.4103/jfmpc.jfmpc_1789_23