World Journal of Hepatology最新文献

Accurate assessment of hepatic steatosis is essential for diagnosing, staging, and monitoring metabolic dysfunction-associated steatotic liver disease. This review comprehensively overviews conventional and emerging hepatic steatosis evaluation methods. Noninvasive imaging techniques such as ultrasound, controlled attenuation parameter, and magnetic resonance imaging-derived proton density fat fraction are discussed alongside invasive reference standards such as liver biopsy. The review also highlights the role of blood-based biomarkers, including fibroblast growth factor 21, cytokeratin-18, type III procollagen peptide, and Mac-2 binding protein glycosylation isomer, as well as novel approaches such as epigenetic markers, artificial intelligence-assisted imaging, and digital pathology. Each method is presented with consideration of its diagnostic performance, clinical utility, and limitations. By integrating these modalities into multimodal assessment strategies and incorporating dynamic endpoints such as magnetic resonance imaging-derived proton density fat fraction (known as magnetic resonance imaging-derived proton density fat fraction)-based fat reduction as a therapeutic response marker, clinicians can improve diagnostic accuracy, risk stratification, and therapeutic guidance.

Background: Progressive familial intrahepatic cholestasis type 3, caused by mutations in the ABCB4 gene, is a rare genetic disorder. Although severe phenotypes due to biallelic mutations are well described, emerging data seem to suggest the clinical relevance of monoallelic variants.

Aim: To describe the clinical spectrum and genotype-phenotype correlation of ABCB4 mutations in children in a cohort of North Indian children.

Methods: This is a retrospective analysis of a prospectively maintained database from a single tertiary care centre. Children (≤ 18 years) with ABCB4 mutations between January 2021 and March 2025 were analysed. The clinical presentation, laboratory investigations, genetic sequencing and outcomes were recorded. Patients were stratified into group 1 (homozygous/compound heterozygous) and group 2 (heterozygous). Variant pathogenicity was assessed using the American College of Medical Genetics guidelines and available predictive tools.

Results: Of the 26 patients, 16 had biallelic mutations, and 10 had monoallelic mutations. Group 1 exhibited higher rates of positive family history (75% vs 30%, P = 0.04), ascites (43.2% vs 0%, P = 0.02), larger varices (40% vs 0%, P = 0.009), higher gamma glutamyl transferase levels (171 U/L vs 38 U/L, P = 0.007), and lower platelet counts (162 × 10⁹/L vs 415 × 10⁹/L, P = 0.007). Notably, two-thirds of patients in group 1 experienced disease progression, and one-third died during follow-up. Certain missense variants (e.g., c.2860T>C) and all nonsense variants were linked to rapid deterioration. Most children in group 2 had transient cholestasis with a good outcome, but two older children succumbed.

Conclusion: Mutations in the ABCB4 gene contribute significantly to pediatric chronic liver disease. Patients with severe biallelic mutations frequently experience a progressive disease course, whereas those with monoallelic mutations may progress slowly. Genetic testing for ABCB4 should be considered in children with cryptogenic chronic liver disease, especially those with high gamma-glutamyltransferase cholestasis and portal hypertension.

Artificial intelligence (AI) has made remarkable strides, becoming an essential tool in modern medicine. As AI continues to evolve, it is crucial to redefine its scope, classifications, and subtypes to better align with its clinical applications and potential. With a growing number of sophisticated models, AI is now widely used in gastroenterology and hepatology, offering new ways to enhance patient care. In gastroenterology, AI helps doctors identify lesions during endoscopy, detect gastrointestinal bleeding, and support the diagnosis and treatment of conditions like inflammatory bowel disease and gastrointestinal cancers. In hepatology, it aids in staging liver fibrosis, tracking disease progression, and predicting hepatocellular carcinoma risks. Machine learning further personalizes treatment plans, helping physicians make more informed decisions. However, despite its promise, AI still faces hurdles, including biases in data, ethical considerations, regulatory challenges, and the need for better transparency. Moving forward, refining these models, conducting extensive validation studies, and integrating AI seamlessly into clinical practice will be crucial in fully realizing its benefits for gastroenterology and hepatology.

A study by Twohig et al evaluated the impact of an educational video module (EVM) on the treatment of alcohol use disorder (AUD) in hospitalized patients with alcohol-related liver disease (ALD). This single-center prospective study involved 42 patients, and the results were compared with those of a retrospective control group. EVM increased the rates of pharmacological (50% vs 22%, P = 0.0008) and psychosocial (73.8% vs 44%, P = 0.001) treatments within 30 days post-treatment. The rate of alcohol relapse decreased significantly (7.9% vs 35.6%, P = 0.003) after the intervention. All the participants recommended the EVM. These findings suggest that standardized educational interventions can address knowledge gaps and improve treatment engagement for AUD in patients with ALD.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is abundantly expressed by hepatocytes and regulates the uptake of low-density lipoprotein by these parenchymal cells. Little research has been conducted on PCSK9 expression in non-hepatocyte liver cells.

Aim: To investigate PCSK9 levels in the supernatant of different liver cells and its regulation in hepatic stellate cells (HSCs).

Methods: PCSK9 levels were measured in the cell culture medium of primary human hepatocytes, HepG2 and Huh7 cells, primary human HSCs, the HSC cell line LX-2, primary human Kupffer cells, and primary human sinusoidal endothelial cells. The effects of cytokines, adipokines, lipopolysaccharide, transforming growth factor beta (TGF-β) and ligands of nuclear receptors on PCSK9 levels in LX-2 cells during 24 hours of culture were determined using enzyme-linked immunosorbent assay.

Results: Primary human hepatocytes, HepG2, Huh7, HSCs, and LX-2 cells secreted significant levels of PCSK9. There were low levels of PCSK9 in the supernatant of Kupffer cells and sinusoidal endothelial cells. Interleukin-6 reduced PCSK9 in LX-2 cells to 86% of controls and lipopolysaccharide increased it by 7%, whereas tumor necrosis factor, as well as exogenous adiponectin and leptin had no effect. Chemerin-156, but not chemerin-155 or chemerin-157 isoform overexpressed in LX-2 cells, reduced PCSK9 to 84% of the controls. TGF-β reduced PCSK9 in LX-2 cell culture media to 68% of controls and lowered its cellular level. Activation of liver X receptor but not farnesoid X receptor or peroxisome proliferator-activated receptor gamma, reduced PCSK9 levels by 42% in LX-2 cell culture medium.

Conclusion: Profibrotic TGF-β and the antifibrotic liver X receptor ligand both reduced PCSK9 in LX-2 medium, showing that PCSK9 is not a marker of HSC activation.

Background: The model for end-stage liver disease (MELD) score helps assess the severity of liver disease and can predict survival after liver transplant. The Charlson comorbidity index (CCI) is frequently employed to forecast the 10-year survival probability of patients with multiple health conditions. We employed the CCI to evaluate the impact of comorbid health conditions on patients and assess its predictive capability regarding health complications and mortality following living donor liver transplantation (LDLT).

Aim: To understand the prevalence of extrahepatic comorbidities in our cohort of LDLT patients with modified CCI (mCCI) and to analyze the utility of mCCI as a predictor of morbidity and mortality following LDLT.

Methods: After obtaining institutional ethics committee approval, a retrospective analysis was conducted on 497 adult patients who underwent LDLT at our institute between January 2021 and December 2023.

Results: Our analysis revealed that the area under the curve (AUC) of the original CCI for predicting 90-day mortality decreased when malignancy was assigned a score of 2 in patients with hepatocellular carcinoma undergoing transplantation. Therefore, we used a mCCI. Both MELD and mCCI scores demonstrated predictive value for 90-day mortality, with AUCs of 0.60 and 0.62, respectively. Using regression coefficients, we developed a composite score defined as: Combined score = [mCCI + (MELD/10)]. This composite metric improved predictive accuracy, yielding an AUC of 0.70 for 90-day mortality prediction. Patients with a CCI > 3 and a MELD > 21 had a significantly higher 90-day mortality rate than others (12.5% vs 5.7%; P = 0.02).

Conclusion: The mCCI was independent of decompensation and overall disease severity. Combining MELD and CCI scores enhanced the discriminatory power for predicting morbidity and 90-day mortality.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as non-alcoholic fatty liver disease, is a major cause of end-stage liver disease worldwide. Numerous studies have demonstrated that the liver is predominantly influenced by environmental and lifestyle risk factors that lead to obesity and diabetes, excessive alcohol consumption, and exposure to environmental pollutants. Microplastics (MPs) are a significant global concern, having been detected in human blood, lungs, kidneys, and liver, and may have deleterious effects on these tissues. Although the effects of MP exposure on the liver have only been partially elucidated, further research is necessary to integrate the direct and extrahepatic effects of MPs on the pathogenesis of MASLD. This review offers a comprehensive analysis of the impact of MPs on hepatic metabolism, including their effects on mitochondrial homeostasis and the endocrine system, with potential implications for the progression of MASLD.

Background: Steatotic liver disease (SLD) including metabolic dysfunction-associated SLD is the most prevalent chronic liver disease worldwide and is strongly associated with metabolic dysfunction as well as chronic hepatitis C (CHC).

Aim: To compare the characteristics of patients with CHC virus infection and the treatment with direct-acting antivirals (DAAs), considering the presence of SLD comorbidity.

Methods: The study included all consecutive hepatitis C virus-infected patients treated with pangenotypic DAA regimens at a single tertiary hepatology center in 2018-2024. SLD was diagnosed via abdominal ultrasound.

Results: Among 688 patients included in the study, 290 (42.2%) had comorbid SLD. The highest prevalence (62.3%) was observed in patients infected with genotype 3. The SLD group was predominantly male (62.8%), in contrast to the non-SLD group, where women predominated. Patients with SLD were significantly older (P = 0.0007), had a higher body mass index (P < 0.0001), and more frequently presented with diabetes (P = 0.01), obesity (P < 0.0001), hyperlipidemia (P = 0.004), and a history of alcohol abuse (P < 0.0001). They also had more advanced liver disease as indicated by a higher rate of cirrhosis (35.5% vs 12% in the non-SLD group, P < 0.0001), elevated aminotransferase activity (P < 0.0001), bilirubin concentration (P < 0.0001), and international normalized ratio values (P = 0.0001), and lower albumin concentration (P = 0.0028). While most patients in both groups completed treatment as planned, adverse events, including severe events and deaths, were more frequent in the SLD group. A sustained virologic response was achieved in 97.6% of the overall population but was significantly lower among patients with SLD compared to the non-SLD group (95.6% vs 99.0%, P = 0.0081). However, logistic regression analysis did not identify SLD as an independent predictor of treatment failure.

Conclusion: Comorbid SLD was common among CHC patients treated with DAAs and was associated with adverse baseline characteristics, including older age, higher body mass index, greater comorbidity burden, and more advanced liver disease. Although SLD patients achieved slightly lower rates of sustained virologic response, SLD itself was not an independent predictor of treatment failure. These findings suggest that poorer treatment outcomes in this subgroup are largely attributable to coexisting risk factors rather than SLD per se, highlighting the need for comprehensive management of metabolic and liver-related comorbidities to optimize antiviral therapy outcomes.

Background: Glucocorticoids (GC) are the cornerstone in the treatment of severe alcohol-associated hepatitis (SAH) but may be associated with adverse events.

Case summary: We report a prospective series of patients with SAH who were treated with GC and developed de novo arthropathy within 2 weeks of GC cessation. Five patients were included in this series, three of whom were women. All patients underwent ultrasound evaluation and were referred to the Rheumatology Clinics. Final diagnoses were: Arthralgia associated with GC cessation (n = 3), polymyalgia rheumatica (n = 1) and psoriatic arthritis (n = 1). Joint soreness was the main symptom, whereas arthritis occurred rarely. Patients with arthralgia associated with GC cessation required longer regimes of GC and tapering strategies but remained free of symptoms and specific treatment in the long term.

Conclusion: De novo arthropathy may occur following GC for SAH. Close monitoring and tapering regimes are advised.

Metabolic dysfunction-associated steatohepatitis (MASH) and alcoholic steatohepatitis (ASH) are severe forms of chronic liver disease, characterized by inflammation, oxidative stress, lipid dysregulation, and fibrosis. Epigenetic changes, including acetylation, methylation, phosphorylation, ubiquitination, sumoylation, and lactylation of histones, dynamically regulate gene expression by altering the chromatin structure. Emerging evidence highlights histone modifications as chief contributors to the pathogenesis of chronic liver diseases. Lactylation which is a novel post-translational modification (PTM) of histone, has been observed as a crucial contributor to liver physiology as well as pathobiology. This modification, characterized by the addition of lactate to lysine residues on histones, influences gene expression and cellular metabolism in the liver. Intriguingly, elevated lactate levels in the liver, resulting from either chronic alcohol consumption or a high-fat/fructose-rich diet, may promote histone lactylation, particularly at histone 3 at lysine 18 (H3K18), which facilitates the transcription of pro-inflammatory and fibrogenic genes. This process not only intensifies hepatic inflammation and fibrosis but also disrupts normal metabolic pathways, resulting in further liver damage. This review aims to elucidate the role of histone lactylation in MASH. Although a direct demonstration of histone lactylation in ASH has not yet been reported, the altered lactate metabolism in ASH suggests that histone lactylation may significantly contribute to its pathogenesis. Finally, we explore novel strategies targeting histone lactylation to mitigate liver injury and improve disease management in MASH and ASH.