World Journal of Hepatology最新文献

In this article, the author comment on the article by Zang et al. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) was examined in this study as a novel biomarker to predict the efficiency of ursodeoxycholic acid (UDCA) and thereby improved primary biliary cholangitis (PBC) treatment. Differentially expressed genes in PBC patients and healthy controls (HCs) were detected using microarray expression analysis. PBC patients and HCs were examined for predictive performance and associations between important genes and clinicopathological features using immunohistochemistry, logistic regression, and receiver operating characteristic curve methods. Thirteen genes linked to the development of PBC were detected by the bioinformatic research. TNFAIP3 was chosen for additional examination from these 13 genes. TNFAIP3 was shown to be more expressed in PBCs patients than in HCs using immunohistochemical method. TNFAIP3 and fatigue have a significant impact on UDCA in PBC patients in multivariate cox regression analysis. Additionally, there was a correlation between TNFAIP3 expression and splenomegaly, alkaline phosphatase, albumin, total bilirubin, and age. In conclusion, TNFAIP3 and fatigue have significant impact on UDCA in PBC. These findings provide a new view on PBC pathophysiology and suggest that TNFAIP3 may be a suitable biomarker or therapeutic target for the disease.

Background: Liver cirrhosis often leads to significant impairments in functional capacity, which are associated with disease severity and prognosis. Simple, reliable, and low-cost tests are essential to monitor these patients in clinical practice. The 6-min walk test (6MWT) is widely used in other chronic conditions, but its measurement properties in cirrhosis remain underexplored.

Aim: To assess the reliability of the 6MWT in patients with liver cirrhosis (LC).

Methods: This cross-sectional study was conducted at a teaching hospital in Juiz de Fora-Minas Gerais. Patients diagnosed with LC at any stage of the disease and under clinical follow-up were included. Patients with grade 2 or higher encephalopathy, respiratory, and/or musculoskeletal diseases or who did not understand the test were excluded. Initially, anamnesis and anthropometric evaluation were performed, followed by the 6MWT. After 24 h the test was repeated. Descriptive statistics were used to present the data. Continuous variables were tested for normality using the Shapiro-Wilk test. The reliability of the 6MWT was tested through Bland-Altman analysis, typical error of measurement, and intraclass correlation coefficient (ICC) as well as a one-sample t-test. A paired Student's t-test was used to check for differences between means, and Pearson's correlation coefficient was used to verify the relationship between the two moments [first 6MWT (6MWT-1) and second 6MWT (6MWT-2)].

Results: The mean difference between 6MWT-2 and 6MWT-1 was -18.9 m; the lower limit of the Bland-Altman agreement was -83.5 m, and the upper limit was 45.7 m. One participant was excluded from further analyses for being outside these limits. The typical error of measurement was 18.9 m. The ICC showed excellent reliability between the two tests (ICC = 0.97, 95% confidence internal: 0.90-0.99, P < 0.001). The Student's one-sample t-value was -2.35 (P = 0.03). The paired t-value was 2.35 (P = 0.03). Pearson's correlation coefficient between the 6MWT-1 and 6MWT-2 was r = 0.98 (P = 0.0001).

Conclusion: The 6MWT is a test with excellent reliability. It is safe, easy to administer, inexpensive, and can be introduced into routine practice without loss of diagnostic precision in estimating the functional capacity of patients with LC.

PANoptosis is an inflammatory programmed cell death pathway possessing critical characteristics of apoptosis, pyroptosis, and necroptosis. It is regulated by PANoptosome complexes, involves interaction between these three key programmed cell death pathways, yet is distinct from any alone. PANoptosis holds vital significance in liver-related diseases, particularly hepatocellular carcinoma (HCC). This article summarizes research on the mechanism and treatments of PANoptosis in HCC. Current research has partially elucidated PANoptosis-related mechanisms in HCC and identified several molecules modulating it. Therapeutic strategies targeting PANoptosis hold significant promise. Investigations into these critical molecules have led to the development of traditional targeted drug therapies and emerging strategies like nanotechnology-based immunocombination therapies. However, there are still challenges in the mechanistic and pharmacological studies of PANoptosis in HCC, including the bidirectional regulation of key apoptotic factors, specific molecular mechanisms, and preclinical models. This article offers a new orientation for studying the pathogenesis and potential therapeutic strategies for HCC.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common and increasingly prevalent condition in the Middle East, but its determinants in the region are underexplored. Diet and lifestyle are known to significantly influence MASLD progression.

Aim: To assess energy and nutrient intake among MASLD patients living in Qatar and evaluate their dietary patterns.

Methods: Using a cross-sectional design, 94 Arab patients with MASLD, aged ≥ 18 years, living in Qatar were studied. MASLD was diagnosed using ultrasonography, fibro scan, or elastography. Sociodemographic information was collected using a self-administered questionnaire. Dietary intake was assessed through three 24-hour recalls and a qualitative food frequency questionnaire. Energy, macro-, and micronutrient intake were analyzed using Elizabeth Stewart Hands and Associates Food Processor^® Nutrition Analysis software. Statistical analyses, including factor loadings were performed using STATA 18.

Results: Compared to recommended dietary allowance, MASLD patients had high intakes of fat, saturated fat, and cholesterol. They also showed reduced intakes of vitamin K in men, and vitamins E and A (retinol), calcium and magnesium in both genders, while selenium and sodium intakes were higher than recommendations. Three dietary patterns were identified: The 'Traditional Qatari food' pattern, the 'Prudent' pattern, and the 'Fast-food' pattern. However, no significant associations were found between these dietary patterns and body mass index or low-density lipoprotein, using adjusted regression models.

Conclusion: Findings warrant replication in longitudinal studies and call for dietary interventions to reduce energy density and enhance overall diet quality, including micronutrient intake, for MASLD prevention and management in the region.

This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease (MASLD), vitamin D3, and severe gastric autonomic neuropathy (diabetic gastric motility disorders) in type 2 diabetes mellitus (T2DM). We question the necessity of excluding patients with severe cataract (unable to complete fundus exams), as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant. We emphasize vitamin D3's multifaceted relevance: It associates with T2DM (high-dose supplementation reduces onset risk), MASLD (serum levels predict risk), smooth muscle function, immunity, and T2DM-related fractures via advanced glycation end products. We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses (e.g., correlation, area under the curve) to refine factor analysis. Additionally, based on the authors' note of vitamin D3-tryptophan metabolism links, we call for deeper integration of metabolic pathways to clarify vitamin D3's role in smooth muscle electrophysiology, leveraging the team's prior research insights.

Drug-induced autoimmune-like hepatitis (DI-ALH) is an increasingly recognized phenotype within the spectrum of drug-induced liver injury. Several drugs, including nitrofurantoin, minocycline, hydralazine, methyldopa and infliximab, have a well-documented capacity to induce DI-ALH. Distinguishing DI-ALH from classic de novo autoimmune hepatitis (AIH) can be challenging due to overlapping clinical, biochemical, and serological features. Accurate distinction from classic AIH is crucial, as management and prognosis differ. While some DI-ALH cases resolve spontaneously after drug withdrawal, others show persistent or worsening liver injury. Histological studies have shown that fibrosis and cirrhosis are more prevalent in classic AH. Unfortunately, there are no pathognomic clinical, biochemical or immunological features that reliably distinguish DI-ALH from classic AIH. However, most patients with DI-ALH do not relapse after corticosteroid withdrawal, in contrast to the high relapse rate observed in classic AIH. Most patients respond well to corticosteroids, and once liver tests normalize, biochemical parameters should be monitored, and long-term immunosuppression should not be indicated. However, DI-ALH is not exempt from risk of relapse, underscoring the need for long-term follow-up. Most patients with DI-ALH have a favorable prognosis; however, although rare, cases of cirrhosis and, in exceptional instances, acute liver failure have been reported. International collaborative studies are needed to further characterize DI-ALH. In this review, we update current controversies, present emerging concepts, and outline future challenges in the diagnosis and management of this complex condition learned so far.

Background: Serum cytokeratin 18 fragment (CK18F) has been developed as a new non-invasive test (NIT) for risk assessment of steatotic liver disease (SLD); however, there are few reports on its relationship with existing NITs and association with cardiometabolic risk factors (CMRFs).

Aim: To clarify the relationship among CK18F, NITs, and CMRF.

Methods: We included 125 patients who were assessed for SLD and had CK18F measured in cross-sectional study. The fibrosis-4 index (FIB-4), steatosis-associated fibrosis estimator (SAFE) score, liver stiffness (LS), controlled attenuation parameter, and FibroScan-aspartate aminotransferase (FAST) score were compared with CK18F as existing NITs.

Results: CK18F was associated with aspartate aminotransferase, alanine aminotransferase, and triglyceride (TG). FAST and SAFE score were associated with high CK18F (> 260 U/L), but not FIB-4 or LS. The cut-off values for TG and high-density lipoprotein (HDL) cholesterol used to determine high CK18F using receiver operating characteristics analysis were 126 mg/dL and 56 mg/dL respectively. High TG (> 126 mg/dL) and low HDL (< 56 mg/dL) were associated with high CK18F. The risk of high CK18F was higher when high TG and low HDL were combined than when each was present alone. CMRF was higher in the high CK18F group, but was not associated with CK18F levels. However, when the TG and HDL criteria for CMRF were replaced by TG > 126 mg/mL and HDL < 56 mg/dL, modified CMRF (mCMRF) was associated with CK18F levels, with a higher risk of high CK18F than CMRF.

Conclusion: CK18F is a new NIT associated with SAFE score and FAST. High TG, low HDL, and mCMRF are associated with high CK18F.

Nonalcoholic fatty liver disease, recently termed metabolic dysfunction-associated steatotic liver disease, affects 25% of adults globally, with a prevalence reaching 93% in obese individuals. The MANPOWER study, a post hoc analysis of 2843 Russian patients with newly diagnosed nonalcoholic fatty liver disease, evaluated Essentiale Forte N^® [essential phospholipids (EPLs)] therapy and a liver enzyme-based staging algorithm. Using generalized linear regression and McNemar tests, EPLs reduced liver enzyme levels (alanine aminotransferase: -20.4 U/L, aspartate aminotransferase: -16.9 U/L, gamma-glutamyl transferase: -17.1 U/L at 24 weeks, P < 0.001) and improved ultrasonography findings (76.8% reduction in hyperechogenicity, P < 0.001). A logistic regression algorithm using alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels achieved 72.3% accuracy, 75.6% sensitivity, 71.0% specificity, and an area under the receiver operating characteristic curve of 0.74 (95% confidence interval: 0.71-0.77) for identifying nonalcoholic steatohepatitis. These findings advocate EPLs as a safe, effective therapy and propose a scalable diagnostic tool, urging validation to reduce the reliance on biopsy.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, necessitating advanced diagnostic tools to improve early detection and personalized targeted therapy. This review synthesizes evidence on explainable ensemble learning approaches for HCC classification, emphasizing their integration with clinical workflows and multi-omics data. A systematic analysis [including datasets such as The Cancer Genome Atlas, Gene Expression Omnibus, and the Surveillance, Epidemiology, and End Results (SEER) datasets] revealed that explainable ensemble learning models achieve high diagnostic accuracy by combining clinical features, serum biomarkers such as alpha-fetoprotein, imaging features such as computed tomography and magnetic resonance imaging, and genomic data. For instance, SHapley Additive exPlanations (SHAP)-based random forests trained on NCBI GSE14520 microarray data (n = 445) achieved 96.53% accuracy, while stacking ensembles applied to the SEER program data (n = 1897) demonstrated an area under the receiver operating characteristic curve of 0.779 for mortality prediction. Despite promising results, challenges persist, including the computational costs of SHAP and local interpretable model-agnostic explanations analyses (e.g., TreeSHAP requiring distributed computing for metabolomics datasets) and dataset biases (e.g., SEER's Western population dominance limiting generalizability). Future research must address inter-cohort heterogeneity, standardize explainability metrics, and prioritize lightweight surrogate models for resource-limited settings. This review presents the potential of explainable ensemble learning frameworks to bridge the gap between predictive accuracy and clinical interpretability, though rigorous validation in independent, multi-center cohorts is critical for real-world deployment.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with approximately 35%-50% of patients presenting concurrent portal vein tumor thrombus (PVTT). Untreated HCC patients with PVTT have a median survival of only 2.5-4 months, posing significant challenges to liver transplantation outcomes. Downstaging therapies play a pivotal role in improving transplant eligibility rates and optimizing post-transplant outcomes. This systematic review summarizes current downstaging therapies, including transarterial chemoembolization, transarterial radioembolization, proton beam therapy, intraportal radiofrequency ablation, and other novel systemic modalities. In-depth analysis of their clinical applications, efficacy, and safety profiles were performed. Furthermore, the review critically evaluates future challenges, including optimized downstaging criteria, personalized and precision medicine approaches, and novel biomaterials for localized therapy for downstaged HCC patients. This review provides comprehensive theoretical and practical insights into pre-transplant downstaging for HCC with PVTT, while highlighting critical avenues for future research and clinical decision-making.