World Journal of Hepatology最新文献

Background: Hepatic encephalopathy (HE) is a poorly understood complication in hepatosplenic schistosomiasis (HSS), a neglected cause of non-cirrhotic portal hypertension. Although portosystemic shunts (PSS) are commonly observed in HSS patients, the prevalence and clinical impact of overt HE (OHE) and minimal HE (MHE) remain understudied, particularly in resource-limited settings.

Aim: To determine OHE/MHE prevalence in HSS and its associations with PSS, clinical, and laboratory characteristics.

Methods: This cross-sectional study included 200 HSS patients undergoing treatment at the Hospital of Universidade Federal de Pernambuco in Brazil between 2021 and 2023. Cognitive function was assessed using the animal naming test (ANT) and Mini-Mental State Examination (MMSE), while psychological status was evaluated with the Hospital Anxiety and Depression Scale. PSS was identified via ultrasound, and fibrosis severity was quantified using the Coutinho index (CI). Analyses were adjusted for education level and the presence of comorbidities. Statistical analyses were performed using R software.

Results: The prevalence of OHE was 0.5%, while MHE, diagnosed via ANT, affected 24% of patients. ANT positivity was significantly associated with the presence of PSS (35.1% vs 15.1%; P = 0.0018) and higher CI scores (1.79 ± 0.26 vs 1.30 ± 0.84; P = 0.045). Patients with MHE demonstrated notably lower MMSE scores (24.06 ± 1.17 vs 26.04 ± 0.63; P = 0.0003), independent of education level. The ANT showed high diagnostic robustness, even among patients with limited formal education.

Conclusion: MHE is prevalent in HSS, especially with PSS, and is associated with portal hypertension severity. The ANT enables practical screening, underscoring the need for routine assessment to improve outcomes.

Background: The norursodeoxycholic acid (norUDCA), a side chain-shortened derivative of ursodeoxycholic acid, exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Aim: To evaluate the efficacy, safety, and tolerability of norUDCA 1500 mg compared to placebo in the patients with MASLD.

Methods: This phase III, randomized, double-blind, multi-centric, placebo-controlled trial enrolled patients with MASLD, and were randomized in 2:1 ratio to receive either norUDCA 1500 mg or placebo for 24 weeks. Efficacy and safety were rigorously evaluated through clinical, biochemical, and imaging assessments. Primary endpoints assessed alanine aminotransferase (ALT) normalization and improvement in liver stiffness (FibroScan^®) at week 12, while secondary endpoints included changes in nonalcoholic fatty liver disease fibrosis score, liver enzymes, lipid profile, glycosylated hemoglobin, and FibroScan-assessed liver stiffness. Safety was monitored throughout the study.

Results: Of 165 randomized patients, 110 received norUDCA and 55 placebos. At week 12, ALT normalization was achieved in 89% of norUDCA-treated group compared to 76% of placebo-treated group (P = 0.022); with a statistically significant adjusted mean difference (P = 0.016). Fibrosis improvement was observed in 57% of norUDCA-treated vs 40% in placebo-treated (P = 0.035), with highly significant adjusted mean (P = 0.002). nonalcoholic fatty liver disease fibrosis score at week 18 and 24 (P = 0.041 and P = 0.032). Similarly, ALT reductions were significant at both week 18 and week 24 (P = 0.021 and P = 0.035). Improvements in lipid profile trended towards norUDCA without statistical significance. Liver stiffness has improved in 90 patients in norUDCA-treated vs 36 patients in placebo group (P = 0.009). NorUDCA demonstrated favorable safety profile, with no serious adverse events reported, and only mild to moderate adverse events were observed.

Conclusion: NorUDCA 1500 mg demonstrated clinically meaningful therapeutic efficacy in patients with MASLD, accompanied by consistently favorable safety profile.

Background: Autoimmune hepatitis (AIH) is characterized by inflammation, hepatocyte necrosis, autoantibodies, and elevated serum globulin levels. It can present at any age, with peaks reported at 30 years and after 60 years. No national studies have evaluated the impact of age at diagnosis on AIH presentation and outcomes.

Aim: To compare the presentation and progression of AIH in patients diagnosed before and after the age of 60 years.

Methods: This cross-sectional analytical study included biopsy-confirmed AIH patients with at least one year of follow-up at Hospital Clínico Universidad de Chile, Santiago, Chile. Demographic, clinical, laboratory, and treatment response variables were analyzed. Group comparisons (diagnosis before or after 60 years) were performed using the χ ² test for qualitative variables and the Mann-Whitney test for quantitative variables (significance P < 0.05).

Results: Ninety-seven AIH patients were included; 85% were female, with a median age of 53 years (range 18-83 years). Forty-one percent were diagnosed after the age of 60. Younger patients exhibited more jaundice at diagnosis (75% vs 44%, P = 0.02) and higher aminotransferases levels (median alanine aminotransferase 998 IU/mL vs 334 IU/mL, P = 0.0002). In contrast, at diagnosis, ascites was more prevalent in patients over 60 (13% vs 2%, P = 0.028), and advanced fibrosis (F3-F4) was more frequent in this group (68% vs 41%, P = 0.020). Biochemical response at six months was similar between groups, despite lower corticosteroid doses being administered to patients over 60 years.

Conclusion: AIH in patients over 60 presented with less jaundice, lower aminotransferases levels, greater fibrosis, and more ascites. Biochemical response was similar independently of age and despite lower prednisone doses administered in patients over 60 years.

Background: Recurrence prediction of hepatocellular carcinoma (HCC) after thermal ablation represents a challenge that can impact patients' quality of life. Artificial intelligence (AI)-based radiomics models applied to various imaging modalities can improve recurrence prediction, therefore guiding therapeutic decisions.

Aim: To evaluate the effectiveness of AI-driven predictive models in predicting HCC recurrence.

Methods: A systematic literature search in PubMed and Scopus was performed, and a total of ten studies were included in this systematic review. All studies included response prediction evaluation with AI models for patients who underwent thermal ablation for HCC. Deep learning and machine learning algorithms were utilized to evaluate the predictive performance and accuracy through metrics such as the area under the curve and concordance index.

Results: The developed models demonstrated high accuracy in predicting local progression and recurrence, allowing a solid risk stratification. In particular, the integration of imaging data and clinical-laboratory variables optimized treatment selection, highlighting the superior ability of imaging models to predict therapeutic outcomes compared to clinical parameters alone. Furthermore, radiomic analysis of follow-up imaging enabled highly accurate detection of ablation site recurrence.

Conclusion: AI-driven predictive models based on multimodal radiomic analyses integrated with clinical data represent promising tools for predicting tumor recurrence after thermal ablation in HCC patients.

Background: Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells (PBMCs) that are associated with infectious, autoimmune, and inflammatory disorders, including chronic liver diseases.

Aim: To identify potential differences in the transcriptome profiles of PBMCs between male patients with non-alcoholic fatty liver disease (NAFLD) and healthy male adolescents.

Methods: PBMCs were isolated from 16 male adolescents with NAFLD and 14 healthy age-matched male peers. The collected cells were cultured in vitro for 18 hours without and with autologous fecal extracts (FEs). Differentially expressed genes (DEGs) were investigated using RNA sequencing. Levels of interleukin (IL)-6, tumor necrosis factor-α, IL-10, and IL-1β secreted into the culture medium were determined using enzyme-linked immunosorbent assays. DEGs were functionally analyzed through annotation according to the Gene Ontology and Reactome databases.

Results: In total, 151 (118 protein-coding) and 97 (65 protein-coding) DEGs were identified when the RNA profiles of PBMCs stimulated without and with FEs, respectively, were compared between NAFLD patients and controls. Functional enrichment analysis of DEGs identified several pathways, which were predominantly involved in metabolism and inflammatory responses in non-stimulated and FE-stimulated PBMCs, respectively. FEs increased secretion of IL-6 and IL-1β by PBMCs isolated from controls and of all four cytokines by PBMCs isolated from NAFLD patients. IL-1β secretion was significantly higher in FE-stimulated PBMCs isolated from NAFLD patients than in those isolated from controls.

Conclusion: Our data suggest that changes in PBMC gene expression may provide candidate biomarkers for NAFLD development, which require validation in larger cohorts.

The gut microbiota is of growing interest to clinicians and researchers due to its elucidating extensive role in metabolic and immune mechanisms, not only in the gut but also in other organs. The liver shares a close bidirectional relationship with the intestine and the gut microbiota. Disturbances in the composition of the gut microbiota can affect the immune systems of both the intestine and liver. In turn, bile composition also influences the gut microbiota. Disruption of this balance can arise from various causes and may significantly impact intestinal and liver health. Therefore, the aim of the current review is to discuss the biological relationships between the gut microbiota and liver function as well as the clinical significance of their disturbances.

Drug-induced liver injury (DILI) is an important but often underrecognized complication in the management of inflammatory bowel disease (IBD), particularly in patients receiving long-term immunomodulatory or biologic therapies. Agents such as thiopurines, methotrexate, anti-tumor necrosis factor agents, and newer small molecules including tofacitinib and upadacitinib have all been implicated in hepatotoxicity, with clinical manifestations ranging from asymptomatic elevations in liver enzymes to severe hepatic injury. Differentiating DILI from hepatobiliary disorders commonly associated with IBD, such as primary sclerosing cholangitis, metabolic dysfunction-associated steatotic liver disease, and autoimmune hepatitis, remains a significant diagnostic challenge. The absence of standardized monitoring protocols, coupled with the variable latency and heterogeneous presentation of DILI, further complicates early recognition and management. In this narrative review, we synthesize current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of DILI in IBD. We also outline diagnostic strategies, including the role and limitations of causality assessment tools, and propose practical considerations for baseline evaluation, longitudinal monitoring, and therapeutic decision-making.

Background: Hepatic ischemia reperfusion (HIR) injury is a major complication affecting various major liver surgeries, including liver transplantation. Aprepitant (APRE), a neurokinin-1 receptor antagonist, is commonly used as an antiemetic to prevent chemotherapy-induced nausea and vomiting.

Aim: To assess the potential protective effect of APRE against HIR-induced liver injury via targeting the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing receptor 3/interleukin (IL)-1beta signaling pathway.

Methods: Six groups of adult male Wistar albino rats were divided as follows: Sham group, Sham/APRE10 group (APRE 10 mg/kg), HIR group, HIR/APRE5 group (APRE 5 mg/kg), HIR/APRE10 group (APRE 10 mg/kg), and HIR/APRE20 group (APRE 20 mg/kg). Serum alanine transaminase, aspartate transaminase, liver malondialdehyde, total antioxidant capacity levels, as well as IL-6, sirtuin 1 (Sirt1), caspase-3, cleaved caspase-3, and tumor necrosis factor alpha biomarkers, were evaluated. Hepatic specimens were examined histopathologically and immunohistochemically for nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression.

Results: HIR resulted in hepatic damage, as evidenced by histopathological changes and a significant increase in serum alanine transaminase, aspartate transaminase, hepatic malondialdehyde, caspase-3, and tumor necrosis factor alpha levels. Additionally, there were significant increases in hepatic total antioxidant capacity and reductions in IL-6 and cleaved caspase-3 protein levels, as demonstrated by Western blot analysis, along with enhanced immunoexpression of Sirt1 and Nrf2. APRE has significantly reduced various parameters of oxidative stress, inflammation, and apoptosis, and a significant increase in liver Nrf2 immunoexpression, leading to a significant improvement in the histopathological changes.

Conclusion: In conclusion, targeting the Sirt1/Nrf2 signaling pathway, as demonstrated by APRE in our model, could present a promising therapeutic target to protect against HIR-induced liver injury during major liver surgeries.

Metabolic-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, yet reliable tools for prognostication remain limited. Fibrosis-based indices such as the fibrosis-4 and nonalcoholic fatty liver disease fibrosis score are widely used but primarily reflect structural damage rather than functional decline. The albumin-bilirubin (ALBI) score, originally established to assess hepatic reserve in patients with hepatocellular carcinoma, provides a simple and objective measure of liver function derived from routine laboratory parameters. Recent validation and meta-analytic studies have shown that ALBI predicts liver-related outcomes and all-cause mortality across diverse chronic liver disease populations, including MASLD, and offers complementary prognostic information beyond fibrosis-based models. Its simplicity, cost-effectiveness, and compatibility with automated reporting systems make it feasible for integration into clinical workflows and population-level risk stratification. However, interpretation of ALBI should consider potential confounders such as renal dysfunction, inflammation, and Gilbert syndrome, and threshold calibration across ethnic groups remains necessary. The ALBI score represents a promising functional biomarker that could enhance risk prediction and care pathways in MASLD, although prospective, multiethnic, and longitudinal studies remain needed to confirm its prognostic value and define clinically meaningful cut-offs.

Refractory autoimmune hepatitis (AIH) is defined as intolerance of or unresponsiveness to standard immunosuppression and occurs in 10%-20% of children with AIH. Lack of response or slower than expected response to induction of remission with steroids, despite good compliance, might be the first clue to refractory AIH. Refractoriness to treatment is associated with an 11.7 times higher risk for liver transplantation or death due to liver disease. The first and foremost consideration for the management is to assess compliance with treatment. It is then important to re-evaluate the diagnosis, assess alternative aetiologies which can mimic the clinical, serological, and histological features of AIH, and address the presence of extra-hepatic co-morbidities. It is important to consider the specific clinical situations, previous therapy, and prior adverse effects before deciding on the most appropriate treatment regimen in refractory AIH. Consideration also should be given to compliance with previous therapy, need for drug level monitoring, growth potential, available formulations, route of administration of medication, and children's and families' preferences before deciding on the therapy. Treatment should be decided and monitored only in specialized hepatology centers.