Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Inflammaging is a process of cellular dysfunction associated with chronic inflammation, which plays a significant role in the onset and progression of liver diseases. Research on its mechanisms has become a hotspot. In viral hepatitis, inflammaging primarily involve oxidative stress, cell apoptosis and necrosis, as well as gut microbiota dysbiosis. In non-alcoholic fatty liver disease, inflammaging is more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, gut microbiota dysbiosis, and abnormalities in NAD⁺ metabolism. In liver tumors, inflammaging is characterized by weakening of tumor suppressive mechanisms, remodeling of the liver microenvironment, metabolic reprogramming, and enhanced immune evasion. Therapeutic strategies targeting inflammaging have been developing recently, and antioxidant therapy, metabolic disorder improvement, and immunotherapy are emerging as important interventions for liver diseases. This review focuses on the mechanisms of inflammaging in liver diseases, aiming to provide novel insights for the prevention and treatment of liver diseases.
Humans ; Liver Diseases/pathology* ; Inflammation ; Oxidative Stress ; Non-alcoholic Fatty Liver Disease ; Liver Neoplasms ; Gastrointestinal Microbiome

OBJECTIVES: To analyze the multimorbidity patterns and core diseases among hospitalized patients in different age groups and to explore the impacts of multimorbidity patterns on hospitalization costs. METHODS: Electronic medical records of adult inpatients (aged ≥18 years) from Ningbo Medical Center Lihuili Hospital between January 1, 2018, and June 30, 2023 were collected. The multimorbidity status involving 53 specific diseases was analyzed across different age groups. Association rule mining was used to identify common multimorbidity patterns. Complex network analysis was used to identify core diseases within the multimorbidity networks. Generalized estimating equations (GEE) were used to analyze the impact of different multimorbidity patterns on hospitalization costs. RESULTS: The prevalence of multimorbidity among the 359 402 adult inpatients was 38.51%, with higher rates observed in males (43.60%) and elderly patients (58.29%). Association rule mining identified 15 common multimorbidity patterns, which exhibited differences across age groups. The most prevalent multimorbidity pattern overall was "diabetes→hypertension" (support=7.04%, confidence=62.17%, lift=2.17). In the young adult group, the most prevalent pattern was "dyslipidemia→chronic liver disease" (support=1.19%, confidence=53.17%, lift=6.04). In the middle-aged group, it was "diabetes→hypertension" (support=4.84%, confidence=50.28%, lift=2.15). In the elderly group, it was "coronary heart disease, diabetes→hypertension" (support=2.38%, confidence=77.43%, lift=1.63). Complex network analysis revealed that the core diseases within multimorbidity networks differed across age groups. The core disease identified in the young adult group was chronic liver disease (degree centrality=50, betweenness centrality=0.055, closeness centrality=0.963). Core diseases in the middle-aged group included hypertension, chronic liver disease, and diabetes (all with degree centrality=52, betweenness centrality=0.022, closeness centrality=1.000). Core diseases in the elderly group comprised hypertension, diabetes, malignant tumors, chronic liver disease, thyroid disease, anemia, and arrhythmia (all with degree centrality=52, betweenness centrality=0.009, closeness centrality=1.000). Generalized estimating equations analysis indicated that, most multimorbidity patterns were significantly associated with increased hospitalization costs. However, the magnitude of cost increase varied across different multimorbidity patterns. Specifically, hospitalization costs for patients with patterns such as "heart failure→hypertension", "stroke→hypertension", "malignant tumor, diabetes→hypertension", "stroke, diabetes→hypertension", and "diabetes, heart failure→hypertension" were more than double those of patients without any target diseases. CONCLUSIONS Multimorbidity patterns and core diseases among hospitalized patients differ significantly across age groups, and different patterns exert varying impacts on hospitalization costs. These findings underscore the necessity for age-stratified and multimorbidity pattern specific management strategies.
Humans ; Multimorbidity ; Male ; Hospitalization/economics* ; Female ; Aged ; Middle Aged ; Adult ; Age Factors ; Young Adult ; Adolescent ; Diabetes Mellitus/epidemiology* ; Electronic Health Records ; Aged, 80 and over ; Hospital Costs ; China/epidemiology* ; Hypertension/economics* ; Liver Diseases/epidemiology*

BACKGROUND AND OBJECTIVES

Hepatobiliarypancreatic tuberculosis (HBPTB) is a less common form of tuberculosis that often presents as malignancy or lithiasis. Advances in diagnostics and minimally invasive procedures have led to the detection of more patients with milder forms of TB requiring surgical management. Due to the low incidence rates and lack of standardized approaches, additional studies are needed to improve patient outcomes. This study examined the risk factors, diagnostic methods, and treatments for HBPTB patients at the University of the Philippines – Philippine General Hospital (UP-PGH) from January 1, 2014 to December 31, 2021.

This retrospective descriptive study utilized our institutional database to identify patients who underwent a surgical procedure for HBPTB and their associated risk factors. Inclusion criteria required biopsy or microbiologic proof of tuberculous involvement of the biliary tract or nearby structures.

Among a total of 45 patients, the most common admitting diagnosis were HBP tuberculosis (37.8%) and malignancy (35.6%). 47.6% of patients had a previous or concurrent TB exposure. Sixty percent had subclinical malnutrition indicated by normal weight and low albumin. The liver (37.8%) and the bile ducts (33.3%) were the most common organs involved. The most common surgical procedures done were ultrasound-guided liver biopsy, biliary enteric anastomosis, percutaneous transhepatic biliary drainage (PTBD), and endoscopic retrograde cholangiopancreatography with or without stenting (ERCP).

This study provides additional data for clinicians to tailor diagnostic and treatment plans accordingly. Striking a balance between surgical procedures and appropriate anti-tuberculous therapy (ATT) is essential for successful treatment. Local data can be useful to help identify tuberculosis patterns unique to Filipinos and highlight socio-economic factors contributing to this rare presentation of TB.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), now known as Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), is linked to cardiovascular disease. This renaming emphasizes the role of metabolic problems. Coronary artery calcification (CAC) reflects early coronary artery disease, but data on the MAFLD-CAC link is limited. OBJECTIVE: To demonstrate the association between metabolic dysfunction-associated fatty liver disease (MAFLD) based on its criteria and coronary artery calcification, as measured by CT CAC score. METHODS: This single-center retrospective study involved adult Filipino patients who underwent CT CAC scoring between January 2021 and January 2023. Clinical and laboratory data were obtained via review of electronic records. RESULTS: This study involved 147 patients with an average age of 62 years, primarily females (57.14%), and mostly falling into the Obese-Class I category (31.29%). The most common comorbidities were hypertension (95.24%), dyslipidemia (62.59%), and diabetes mellitus (38.1%). In terms of CAC scores using the CT Agatston method, majority (30.61%) had low calcium buildup (Stage 2 with scores between 1-99). Approximately 26.53% had higher liver fat content with liver HU below 40, while 73.47% had lower liver fat content with HU equal to or greater than 40. Furthermore, 25.17% of patients with fatty livers and other risk factors were diagnosed with MAFLD, while 74.83% were not. The p-value indicated a significant difference in proportions, suggesting a lower proportion of MAFLD among those who had undergone CT CAC scoring. However, the Pearson Chi-Square statistic (4.051) and the p-value (0.256) indicated no statistically significant association between MAFLD and CT CAC. CONCLUSION The study found a notably lower proportion of MAFLD diagnoses in patients who underwent CT CAC scoring. Additionally, there was no statistically significant link between MAFLD and CT CAC.
Cardiovascular Diseases ; Coronary Artery Disease ; Fatty Liver, Alcoholic

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with Type 2 Diabetes Mellitus (T2DM) and is associated with chronic kidney disease (CKD). The aim of this cross-sectional study was to determine the association of Fibrosis-4 (FIB-4) index with CKD among T2DM patients with concomitant NAFLD.

A single center, analytical cross-sectional study was conducted among 216 T2DM patients with concomitant NAFLD. Clinical data were obtained via retrospective review of medical charts. The outcome of interest was CKD which was based on self-report obtained from medical charts or estimated Glomerular Filtration Rate (eGFR)RESULTS

Higher FIB-4 index was found to be significantly associated with CKD. Patients with FIB-4 index of 1.45-3.25 (moderate risk) and >3.25 (high risk) have about 3 times higher odds of CKD. However, after controlling for the significant confounders, only those who belong to high-risk group was found to be associated with CKD.

This study has demonstrated that FIB4 index > 3.25, an index of liver fibrosis, is significantly associated with development of CKD in T2DM patients with concomitant NAFLD.

Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism* ; Humans ; Metabolic Diseases/physiopathology* ; Lipid Metabolism/physiology* ; Animals ; Obesity/enzymology* ; Non-alcoholic Fatty Liver Disease

Child ; Humans ; China ; Consensus ; Fatty Liver/therapy* ; Metabolic Diseases/therapy* ; Systematic Reviews as Topic