Pediatric acute liver failure (PALF) is a rare and critical clinical syndrome with a poor prognosis. Its etiology is complex, with a significant proportion of cases having remained classified as indeterminate or cryptogenic PALF. With the application of high-throughput sequencing technologies, a spectrum of disorders caused by specific genetic metabolic defects and characterized by stress-sensitive Recurrent acute liver failure (RALF) has been gradually unveiled, collectively termed Infantile liver failure syndrome (ILFS). Although the molecular mechanisms underlying the subtypes ILFS1, ILFS2, and ILFS3 differ by involving aminoacyl-tRNA synthetase defects, vesicular transport disorders, and autophagy abnormalities, respectively, they share a common clinical phenotype of RALF triggered by fever or infection. This article has systematically reviewed the clinical phenotypic spectrum, molecular genetic characteristics, differential diagnosis strategies, and therapeutic advances of the three ILFS subtypes, with the goal of improving early clinical recognition and precise intervention, and providing an important reference for evaluating the prognosis of different subtypes.
Humans ; Liver Failure, Acute/therapy* ; Infant ; Diagnosis, Differential

OBJECTIVES: To systematically evaluate the prevalence and risk factors of non-alcoholic fatty liver disease (NAFLD) in overweight and obese children and adolescents in China. METHODS: Databases including China National Knowledge Infrastructure, Wanfang Data, VIP Database, China Biomedical Literature Database, PubMed, Embase, Web of Science, and Cochrane Library were searched, from database inception to October 2024. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies according to inclusion and exclusion criteria. A Meta analysis was conducted using Stata 16.0 software. RESULTS: A total of 42 studies involving 16 481 overweight and obese children and adolescents were included. The Meta analysis results showed that the prevalence of NAFLD among overweight and obese children in China was 43% (95%CI: 37%-48%). Factors associated with NAFLD included being male (OR=1.61, 95%CI: 1.17-2.04), increased weight (MD=10.33, 95%CI: 9.08-11.57), increased waist circumference (MD=5.49, 95%CI: 3.36-7.62), longer duration of obesity (MD=0.31, 95%CI: 0.02-0.61), higher body mass index (MD=3.11, 95%CI: 2.07-4.16), elevated fasting blood glucose levels (MD=0.17, 95%CI: 0.06-0.29), higher triglyceride levels (MD=0.32, 95%CI: 0.17-0.47), elevated total cholesterol levels (MD=0.15, 95%CI: 0.10-0.21), higher low-density lipoprotein cholesterol levels (MD=0.14, 95%CI: 0.04-0.23), increased alanine aminotransferase levels (MD=24.39, 95%CI: 18.57-30.20), increased aspartate aminotransferase levels (MD=12.49, 95%CI: 9.67-15.32), elevated serum insulin levels (MD=4.47, 95%CI: 2.57-6.36), higher homeostasis model assessment-insulin resistance (MD=0.45, 95%CI: 0.30-0.59), and elevated uric acid levels (MD=55.91, 95%CI: 35.49-76.32) (P<0.05). CONCLUSIONS The prevalence of NAFLD among overweight and obese children and adolescents in China is high. Male gender, increased weight, increased waist circumference, prolonged obesity duration, higher body mass index, dyslipidemia, and elevated levels of fasting blood glucose, liver enzymes, serum insulin, homeostasis model assessment-insulin resistance, and uric acid are potential risk factors for NAFLD in this population.
Humans ; Non-alcoholic Fatty Liver Disease/etiology* ; Risk Factors ; Adolescent ; Child ; Overweight/complications* ; Prevalence ; China/epidemiology* ; Obesity/complications* ; Male ; Female

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

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*

The clinical data of 10 patients with pathologically confirmed primary hepatic neuroendocrine neoplasms (PHNENs) were retrospectively analyzed. The cohort included 8 males and 2 females, with a median age of 63 years. None presented with carcinoid syndrome. Three cases were detected incidentally during health check-ups, 2 presented with painless jaundice, and 5 reported abdominal distension or pain (1 with concurrent jaundice). Elevated tumor markers included carbohydrate antigen 19-9 in 4 cases, alpha-fetoprotein in 2 cases, and neuron-specific enolase in 1 case. All patients underwent surgical resection, including hepatectomy and hilar cholangiocarcinoma resection, combining with resection and reconstruction of right hepatic artery, resection of liver metastases and pancreaticoduodenectomy according to the extent of tumor invasion.Preoperative imaging failed to diagnose neuroendocrine neoplasms in all cases. Final pathological diagnoses were neuroendocrine tumor (NET) G2 in 5 cases, NET G3 in 1 case, and neuroendocrine carcinoma (NEC) in 4 cases. During the follow-up, 4 patients died and 6 survived. The study demonstrates that PHNENs lack specific clinical or imaging features, and the diagnosis relies on pathological examination after excluding metastatic disease. Radical resection remains the primary treatment, with prognosis varying significantly by tumor grade.
Humans ; Middle Aged ; Male ; Female ; Neuroendocrine Tumors/pathology* ; Liver Neoplasms/pathology* ; Retrospective Studies ; Aged ; Adult

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 common in Type 2 Diabetes Mellitus (T2DM). The FIB-4 index is one of the most-studied non-invasive biomarkers that combines age and laboratory parameters (platelet count, alanine-and aspartate- aminotransferase) to evaluate underlying hepatic fibrosis. This study aims to determine the diagnostic value of Fibrosis-4 (FIB-4) index scoring in screening for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus, which is a high-risk population in development of advance fibrosis.

A single center, analytical cross-sectional study was conducted among adult T2DM patients with and without NAFLD seen at the Out-Patient Department (OPD) and those with NAFLD enrolled under the Liver Disease Databank of the Liver Disease and Transplant Center in collaboration with Research and Biotechnology Division at St. Luke’s Medical Center, Quezon City. Medical history was obtained by reviewing charts of eligible patients using data collection form. Liver ultrasound was used as the reference standard in the diagnosis of NAFLD. The FIB-4 index was calculated with this formula: age (years) x AST (U/L)/(platelets (10^9/L) x ALT (U/L)^1/2.

A total of 305 adult patients with type 2 diabetes mellitus were included in the study. The prevalence of non-alcoholic fatty liver disease based on ultrasound among diabetic patients is 76.07%. The median age (p = 0.0204), AST (p < 0.00001), ALT (p < 0.00001) were significantly higher in patients with NAFLD than those without. Platelet count (p = 0.0002) was significantly lower in patients with NAFLD than those without. The proportion of patients with low platelet count, high AST and high ALT were significantly higher in patients with NALFD than those without. In this study, the FIB-4 index cutoff score for screening of NAFLD is ≥0.76, which has an accuracy of 66.23%, sensitivity of 75%, specificity of 38.3%, PPV of 79.46% and NPV of 32.56% in detecting fatty liver.

A FIB-4 index value of ≥0.76 has an acceptable sensitivity for screening NAFLD even in the absence of fibrosis among patients with T2DM. However, due to its low specificity, additional tests to establish NAFLD diagnosis may be required.

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.