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

BACKGROUND

Tuberculosis (TB) has long been a recognized infectious disease contributory to worldwide mortalities. Most cases are from low- to middle-income countries, including the Philippines. Hepatobiliary TB comprises only a small portion of extrapulmonary TB. Tuberculous liver abscess (TLA) usually presents with nonspecific findings causing delay in the diagnosis. Due to this, further reports are needed for early detection along with timely treatment for future courses.

Presenting a 17-year-old male who came in with right upper quadrant abdominal pain associated with intermittent fever. The symptoms persisted and eventually progressed to abdominal distention, weight loss and jaundice. Initial laboratories were taken including an ultrasound finding of a complex lesion in the hepatic lobe. He was initially managed with empiric antibiotic therapy – Ciprofloxacin and Metronidazole, however, despite it, there was persistence of right upper quadrant pain, abdominal distention and jaundice. Due to this, further work-up was done with drainage of the abscess. Cultures were taken revealing tubercle bacilli along with other microbial growth. Antibiotics and antituberculosis medications sensitive to the microorganisms were started. With the noted improvement of jaundice and abdominal distention and resolution of pain and fever, he was discharged.

 Tuberculous liver abscess is an uncommon presentation of extrapulmonary tuberculosis in an
immunocompetent male with right upper quadrant abdominal pain and jaundice. Although TB is endemic in the
Philippines, this gastrointestinal involvement is often not immediately recognized. Thus, with any suspicion of liver abscess,
tuberculous (TLA) type should be included in the differentials for early diagnosis and management. 

BACKGROUND

Sarcopenia is highly prevalent in patients with liver cirrhosis and contributes to decreased quality of life, increased morbidity, and mortality. The role of myostatin in cirrhosis-related sarcopenia remains controversial but may represent a potential therapeutic target.

This study aimed to investigate the association between serum myostatin levels and sarcopenia in patients with liver cirrhosis.

A cross-sectional study was conducted with 80 patients diagnosed with liver cirrhosis at Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Bali, Indonesia. Serum myostatin levels (ng/L) were measured using an ELISA technique. Sarcopenia was diagnosed based on the 2019 Asian Working Group for Sarcopenia (AWGS) consensus. Elevated myostatin levels were defined as values above the median. Bivariate and multivariate analyses were performed to assess associations between myostatin, cirrhosis severity, and sarcopenia.

The severity of cirrhosis (CTP B and C) was associated with elevated myostatin levels (PR = 2.046; 95% CI: 1.310–3.193; p = 0.002). Bivariate analysis demonstrated that elevated myostatin (PR = 2.178; 95% CI: 1.370–3.461; p < 0.001), CTP B and C (PR = 1.818; 95% CI: 1.223–2.701; p = 0.004), ascites (PR = 1.606; 95% CI: 1.110–2.324; p = 0.034), and malnutrition (PR = 1.806; 95% CI: 1.242–2.626; p = 0.004) were associated with sarcopenia. In multivariate analysis, only elevated serum myostatin remained significantly associated with sarcopenia (AOR = 4.273; 95% CI: 1.557–11.724; p = 0.005).

Elevated serum myostatin levels are strongly associated with sarcopenia in patients with liver cirrhosis. Cirrhosis severity is also linked to higher myostatin levels, suggesting a potential role for myostatin-targeted interventions in sarcopenia management.

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is common among patients with type 2 diabetes (T2D) and increases the risk of cirrhosis, yet fibrosis often remains clinically silent until hepatic decompensation occurs. Current diabetes guidelines recommend noninvasive fibrosis risk stratification, such as the fibrosis-4 index (FIB-4), during routine diabetes care, but real-world adoption remains unclear. This study aimed to evaluate the implementation of FIB-4 as a risk stratification tool in patients with T2D. Methodology: This was a retrospective study of consecutive patients with T2D who were seen in the Diabetes Clinic of University of Malaya Medical Centre in 2023. Patients were identified as having a higher risk of future cirrhosis based on elevated FIB-4 ≥1.3. Results: The data for 1,009 patients were analyzed, median age 62 (52–71) years, 40.7% male. Elevated FIB-4 was seen in 28.8% (291/1,009). Only 12.0% (35/291) with elevated FIB-4 were referred for further hepatology evaluation, whereas 3.3% (24/718) with low FIB-4 were referred. Among the patients with elevated FIB-4, those referred were more likely known to have hepatic steatosis, had higher alanine aminotransferase, aspartate aminotransferase, gammaglutamyl transferase, and lower low-density lipoprotein cholesterol and platelet count. Over a median follow-up of 1.71 (0.99–1.95) years, totaling 1,440 person-years, two liverrelated events (0.2%) occurred (one each in the elevated and low FIB-4 group, respectively). Sixteen patients (4.0%) experienced cardiovascular events, including one patient (0.6%) in the elevated FIB-4 group and 15 (2.9%) in the low FIB-4 group. Conclusion Despite automated FIB-4 reporting, this risk stratification tool was underutilized in T2D, resulting in missed opportunities for early identification and management of more severe liver disease. Integration of FIB-4 into diabetes care workflows, alongside structured referral pathways and clinician education, may improve early detection and reduce long-term hepatic complications in T2D.
Diabetes Mellitus, Type 2 ; Risk Assessment ; Liver Diseases ; Referral and Consultation

Introduction: The global rise in paediatric obesity has led to an increasing burden of metabolic comorbidities, including metabolic dysfunction–associated steatotic liver disease (MASLD). Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia, has been implicated in the pathogenesis of liver injury. This study aimed to evaluate the prevalence of MASLD and its association with OSA among children and adolescents in a tertiary centre. Methodology: A retrospective cross-sectional study was conducted involving children aged 6–15 years who were admitted for polysomnography at Sarawak General Hospital between 2024 and 2025. Clinical, biochemical, and lifestyle data were obtained from medical records and parental questionnaires. Hepatic steatosis was assessed using hepatobiliary ultrasound in a subset of patients. Results: A total of 132 children (mean age 10.8 ± 2.7 years; 87.5% male) were included. The median BMI SDS was 2.50 (IQR: 2.29– 2.93). The mean apnea–hypopnea index (AHI) was 12.0 ± 7.9, with 60% classified as severe OSA. Among the 16 children who underwent liver ultrasound, MASLD was identified in 81.2%, including five cases of grade 1 and eight cases of grade 2 steatosis. Liver transaminitis was present in six patients. Metabolic comorbidities were common, with 43.8% requiring metformin for insulin resistance or impaired glucose tolerance, and four patients requiring antihypertensive therapy. Unhealthy lifestyle behaviors were prevalent: 64.2% consumed sugary drinks ≥3 times weekly, 42.9% consumed fast food ≥3 times weekly, and only 24.3% reported daily fruit or vegetable intake. Physical inactivity (≤2 times/week) was observed in 71.4%, while 64.3% had screen time exceeding 2 hours daily. Conclusion Children and adolescents with moderate-to-severe OSA exhibit a high burden of metabolic dysfunction, including MASLD. The findings support a potential contributory role of OSA-related hypoxia in paediatric fatty liver disease and highlight the need for integrated screening and early intervention in this high-risk population.
Adolescent ; Child ; Malaysia ; Liver Diseases

The gut microbiota is an indispensable symbiotic entity within the human holobiont, serving as a critical regulator of host lipid metabolism homeostasis. Therefore, it has emerged as a central subject of research in the pathophysiology of metabolic disorders. This microbial consortium orchestrates key aspects of host lipid dynamics-including absorption, metabolism, and storage-through multifaceted mechanisms such as the enzymatic processing of dietary polysaccharides, the facilitation of long-chain fatty acid uptake by intestinal epithelial cells (IECs), and the bidirectional modulation of adipose tissue functionality. Mounting evidence underscores that gut microbiota-derived metabolites not only directly mediate canonical lipid metabolic pathways but also interface with host immune pathways, epigenetic machinery, and circadian regulatory systems, thereby establishing an intricate crosstalk that coordinates systemic metabolic outputs. Perturbations in microbial composition (dysbiosis) drive pathological disruptions to lipid homeostasis, serving as a pathogenic driver for conditions such as obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). This review systematically examines the emerging mechanistic insights into the gut microbiota-mediated regulation of intestinal lipid metabolism, while it elucidates its translational implications for understanding metabolic disease pathogenesis and developing targeted therapies.
Humans ; Gastrointestinal Microbiome/physiology* ; Lipid Metabolism ; Animals ; Intestinal Mucosa/metabolism* ; Homeostasis ; Dysbiosis ; Obesity/metabolism* ; Intestines/microbiology* ; Non-alcoholic Fatty Liver Disease/metabolism* ; Metabolic Diseases/metabolism*

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions. Mitochondria are vital organelles that function in diverse metabolic processes in the body, including redox reactions, lipid metabolism, and cell death. Mitophagy, a specific form of autophagy for damaged mitochondria, plays a critical role in the pathophysiology of liver diseases. In this review, we explain in detail the roles of the Nrf2 signaling pathway and mitophagy, and the relationship between them, in various hepatic diseases (nonalcoholic fatty liver disease, viral hepatitis, alcoholic liver disease, drug-induced liver injury, autoimmune hepatitis, hepatic ischemia‒reperfusion injury, and liver cancer). We also offer some potential insights and treatments relevant to clinical applications.
Humans ; NF-E2-Related Factor 2/metabolism* ; Mitophagy/physiology* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; Liver Diseases/etiology* ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Non-alcoholic Fatty Liver Disease ; Liver Neoplasms

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*