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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 =... Jun 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.
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 -
Biomarker Research May 2024Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the... (Review)
Review
Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field.
PubMed: 38816776
DOI: 10.1186/s40364-024-00601-0 -
Cureus Apr 2024Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic...
Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic hepatitis), immunologic (autoimmune hepatitis, primary biliary cholangitis), or as a result of indirect insult secondary to biliary tract dysfunction (cholestatic hepatitis), pregnancy-related liver dysfunction, shock, or metastatic disease. In clinical settings, these causes are not uncommon to overlap with each other or are masked by obviously visible causes in medical history. We reported our scenario of a patient who has a heavy history of alcohol use and presented with alcohol withdrawal symptoms and a marked elevation of liver enzymes. Interestingly, further investigations suggested Wilson's disease could be an underlying culprit of acute hepatitis in this patient. This case again emphasized that Wilson's disease can be masked under multiple causes and various scenarios, which alerts clinicians that a broad approach should be made for every case of acute hepatitis.
PubMed: 38803772
DOI: 10.7759/cureus.59025 -
Aging May 2024Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to...
Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to detect, and several factors contribute to making alcohol difficult to quit. Continued alcohol abuse worsens the condition, meaning it may gradually progress into alcoholic hepatitis and cirrhosis, ultimately, resulting in irreversible consequences. Therefore, effective treatments are urgently needed for early-stage ALD. Current research mainly focuses on preventing the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. However, challenges remain in identifying key therapeutic targets and understanding the molecular mechanisms that underlie the treatment of alcoholic hepatitis and cirrhosis, such as the limited discovery of effective therapeutic targets and treatments. Here, we downloaded ALD microarray data from Gene Expression Omnibus and used bioinformatics to compare and identify the hub genes involved in the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. We also predicted target miRNAs and long non-coding RNAs (lncRNAs) to elucidate the regulatory mechanisms (the mRNA-miRNA-lncRNA axis) underlying this progression, thereby building a competitive endogenous RNA (ceRNA) mechanism for lncRNA, miRNA, and mRNA. This study provides a theoretical basis for the early treatment of alcoholic hepatitis and cirrhosis and identifies potential therapeutic targets.
Topics: Humans; Liver Diseases, Alcoholic; Gene Regulatory Networks; MicroRNAs; RNA, Long Noncoding; Early Diagnosis; RNA, Messenger; Computational Biology; Disease Progression; Gene Expression Profiling; Gene Expression Regulation; RNA, Competitive Endogenous
PubMed: 38795390
DOI: 10.18632/aging.205861