World Journal of Hepatology最新文献

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.

In this editorial, author specifically focuses upon metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver diseases (ALD) in the current era. This editorial article is inspired by the observational study by Harris et al in the recent issue. Alcohol and metabolic dysfunction cause steatotic changes in the hepatic parenchyma. The ALD and MASLD are major cause of chronic liver disease. Liver cirrhosis (LC) is a result of chronic liver inflammation with many causes (e.g., viral hepatitis, drug, alcohol and metabolic disorder). Metabolic dysfunction-associated steatohepatitis and alcohol-associated hepatitis can lead to liver fibrosis and LC. LC leads to hepatic dysfunction and can progress to eventual liver failure and death. Though chronic viral hepatitis is considered a main cause of LC for a long time, other etiologies (i.e., ALD, MASLD) has significantly increased in the current era. From the viewpoint of carcinogenesis, LC frequently causes hepatocellular carcinoma (HCC), and HCC is the most common type of primary liver cancer worldwide. As regards major causes of HCC, chronic viral hepatitis is gradually outweighed by ALD and MASLD. Note that patients coexisting with ALD and metabolic dysfunction-associated steatohepatitis show higher occurrence of HCC. Impact of ALD and MASLD upon the development of chronic liver disease, liver fibrosis, LC, and HCC is drastically increased in the current era. Establishments of diagnostic and therapeutic strategies to overcome these hepatic disorders are still required.

Background: Laparoscopic surgery is increasingly used for complex hepatolithiasis; however, data on laparoscopic vs open surgery remain limited. This study was undertaken to test the hypothesis that laparoscopic surgery offers comparable safety and efficacy to open surgery, with added benefits in recovery outcomes.

Aim: To compare clinical outcomes between laparoscopic and open approaches in complex hepatolithiasis.

Methods: This retrospective cohort study was conducted at Ningde Municipal Hospital, a tertiary care center, and included 80 patients with complex hepatolithiasis treated between January 2020 and August 2024. Patients were non-randomly allocated to laparoscopic (n = 40) or open surgery (n = 40) groups based on the treatment period. Clinical, intraoperative, and postoperative data were analyzed using appropriate parametric or non-parametric tests; categorical data were analyzed using χ ² or Fisher's exact test.

Results: Laparoscopic surgery was associated with a longer median operative time (250.0 minutes vs 207.0 minutes, P = 0.003) but shorter postoperative hospital stay (9.0 days vs 14.0 days, P < 0.001) compared to open surgery. Wound infection rates were significantly less frequent in the laparoscopic group (5.0% vs 22.5%, P = 0.023). Stone clearance rates and overall complications were comparable. One case of perioperative mortality occurred in the open surgery cohort.

Conclusion: Laparoscopic surgery is a feasible and safe alternative to open surgery for complex hepatolithiasis, offering faster recovery and reduced wound-related complications.

Metabolic dysfunction-associated steatotic liver disease (MASLD) requires accurate liver fibrosis assessment for management. While liver biopsy remains the gold standard, its invasiveness drives demand for non-invasive biomarkers. This review evaluates blood biomarkers for MASLD fibrosis staging. Established scores (fibrosis-4, non-alcoholic fatty liver disease fibrosis score) offer accessible screening but exhibit variable performance influenced by age, obesity, and comorbidities. Patented panels (e.g., enhanced liver fibrosis test, FibroMeter) improve accuracy by integrating extracellular matrix or metabolic markers, though context-specific thresholds are essential. Emerging biomarkers like propeptide of type 3 collagen, Mac-2 binding protein glycosylation isomer, epigenetic markers (proliferator-activated receptor-γ methylation), and angiopoietin-like proteins a family of eight glycoproteins show promise but require large-scale validation. Genetic risk scores and multi-omics approaches face generalizability challenges. Integration strategies, such as combining serum biomarkers with liver stiffness measurement via Agile scores, enhance diagnostic precision and reduce indeterminate classifications. Current tools aid risk stratification, but no single biomarker replicates biopsy-level precision. Future efforts must prioritize MASLD-specific diagnostic frameworks, standardized protocols, and multi-modal integration to enhance clinical utility and address MASLD's growing burden.

The evolving nomenclature from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) aims to better encompass the metabolic context of the disease. This change has significant implications for patients with type 2 diabetes mellitus (T2DM), given the frequent overlap between these conditions. This minireview explores the rationale behind the change, compares diagnostic criteria, and evaluates the impact of the MASLD framework on disease prevalence, characterization, and outcomes in T2DM patients. The updated MASLD criteria include all individuals with T2DM and hepatic steatosis, emphasizing metabolic dysfunction as the primary driver. In contrast, the NAFLD definition necessitates excluding other chronic liver diseases and verifying the absence of significant alcohol consumption, leading to a narrower diagnostic framework. Both metabolic dysfunction-associated fatty liver disease and MASLD identify a higher prevalence of steatotic liver disease, particularly among T2DM patients, compared to NAFLD. Notably, the MASLD framework introduces metabolic and alcohol-associated liver disease to account for dual etiologies involving alcohol use, which is common in T2DM populations but previously excluded under NAFLD criteria. While the new definitions enhance clinical relevance and inclusivity, they also highlight challenges such as unrecognized medication-induced steatosis and the need for reclassification in ongoing T2DM clinical trials. Emerging evidence supports enhanced screening strategies (e.g., fibrosis-4) and metabolic-targeted treatments for MASLD in T2DM patients. The successful integration of MASLD into clinical practice will require system-wide reeducation, standardization, and multidisciplinary collaboration to improve outcomes for T2DM patients.