World Journal of Hepatology最新文献

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, affecting more than 30% of adults and 7%-14% of youths globally. MASLD and its advanced form of metabolic dysfunction-associated steatohepatitis (MASH) can progress to liver cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective therapies for MASLD and MASH remain limited. Accumulating evidence indicates that short-chain fatty acids (SCFAs) modulate the activation of hepatic innate and adaptive immune cells, influencing liver inflammation and fibrosis. Moreover, SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity, affecting MASLD progression. This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation, fibrosis, and energy metabolism. Several key molecular signaling pathways are discussed. Clinical trials aiming to modulate SCFA production through different treatments are reviewed. Collectively, emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.

Hypertransaminasemia - acute elevation of alanine aminotransferase and aspartate aminotransferase - is prevalent in non-cirrhotic adults admitted to the intensive care unit (ICU) and often signals extra-hepatic pathophysiology rather than intrinsic liver disease. To synthesise contemporary evidence on aetiology-driven diagnosis, management and emerging biomarkers of hypertransaminasemia in critically ill patients. We performed a structured search of PubMed, EMBASE and CENTRAL (January 2010-June 2025). The search was restricted to full-text articles that were published in English in peer-reviewed journals. Hypoxic liver injury is the leading cause of hypertransaminasemia in non-cirrhotic ICU patients and is characterized by a ≥ 50% alanine aminotransferase/aspartate aminotransferase fall within 72 hours after haemodynamic stabilisation. Idiosyncratic drug-induced liver injury remains uncommon yet explains about 13% of acute liver-failure cases in Western registries. Sepsis-associated liver injury presents mainly as conjugated hyperbilirubinaemia with modest transaminase rise, whereas parenteral-nutrition-associated liver disease is dominated by cholestasis after > 2 weeks of parenteral feeding. Early optimisation of macro-/micro-circulation, rational deprescribing of hepatotoxins, rapid source control of infection and prompt transition to enteral nutrition are outcome-modifying interventions across all phenotypes. In the ICU, aminotransferase elevation should be interpreted as a dynamic biomarker of systemic distress. A pattern-recognition algorithm integrating clinical context, enzyme kinetics and novel biomarkers (glutamate dehydrogenase, microRNA-122, high-mobility group box-1) can expedite aetiology-specific therapy and deserves prospective validation.

Beyond its traditional role in calcium and bone metabolism, vitamin D has emerged as a critical regulator of liver health. Its active form, calcitriol [1α,25(OH)₂D], signals through the vitamin D receptor (VDR), which is expressed in hepatic stellate cells, Kupffer cells, and cholangiocytes. Through this pathway, vitamin D modulates fibrosis, inflammation, oxidative stress, bile acid homeostasis, and immune responses. This review explores the growing body of evidence linking vitamin D deficiency to chronic liver diseases, including autoimmune hepatitis, primary biliary cholangitis, alcoholic liver disease, viral hepatitis B and C, and metabolic-associated steatotic liver disease. Low vitamin D levels are frequently observed in these conditions and are associated with disease severity, complications (such as spontaneous bacterial peritonitis, sarcopenia, and hepatic encephalopathy), and increased mortality. Mechanistically, vitamin D-VDR signaling inhibits profibrotic TGF-β1/SMAD pathways, downregulates proinflammatory cytokines, enhances regulatory T cell differentiation, and improves insulin sensitivity. Although preclinical studies support its protective effects, clinical trials of vitamin D supplementation have produced mixed results. Overall, vitamin D appears to influence multiple pathways in liver disease pathophysiology, and correcting its deficiency may offer clinical benefits. However, its integration into clinical care will depend on identifying responsive patient subgroups and defining optimal dosing strategies to maximize therapeutic benefit.

Steatotic liver disease (SLD) encompasses a group of disorders characterized by the excessive accumulation of fat in the liver. It is classified into four categories based on clinical manifestations: Metabolic dysfunction-associated SLD (MASLD), metabolic-alcohol-associated liver disease (ALD), ALD, and cryptogenic SLD. In the United States, its prevalence stands at 34.2%, making it the most common cause of cirrhosis and hepatocellular carcinoma (HCC). In addition to factors related to endocrine, nutrition, and medications, several genetic markers have been implicated in the disease's pathogenesis. Notable genes include PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13. These genetic polymorphisms can significantly impact prognosis and disease outcomes. For example, PNPLA3 is the most frequently associated gene with MASLD, increasing the risk of HCC by 12-fold and liver-related mortality by 18-fold. Furthermore, certain genetic markers are more prevalent in specific ethnic groups; for instance, PNPLA3 is common among Hispanics, while TM6SF2 is linked to higher fat content in African Americans. With a better understanding of the genetic factors involved in the pathogenesis of SLD, significant advancements have been made in diagnostics and therapeutics. This review explores the role of genetic factors in the disease's development, discusses current advancements in non-invasive diagnostic modalities, and examines therapeutic improvements based on these genetic insights to achieve better outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, represents a growing global health burden, contributing significantly to liver-related morbidity and mortality. Early detection and timely intervention are essential to prevent disease progression. Conventional diagnostic methods, which rely on specialized imaging and invasive liver biopsies, underscore the need for non-invasive, cost-effective alternatives. Artificial intelligence-particularly machine learning and deep learning-has emerged as a transformative tool in MASLD diagnostics, offering improved accuracy in risk prediction, imaging interpretation, and disease stratification. This review synthesizes recent advancements in AI-based MASLD diagnostics, highlighting key models, performance metrics, and clinical applications, while addressing ongoing challenges such as data standardization, interpretability, and clinical validation.

Hepatocellular carcinoma (HCC) is imposing a growing global health burden, with China accounting for nearly half of incident cases and mortality worldwide. Early screening is critical to improving survival in high-burden regions. However, the global standardized screening rate for high-risk populations is less than 24%, and HCC screening currently faces severe challenges. We synthesize recent advances in HCC screening, including optimized serum biomarkers, evolving imaging techniques, and validated models. Emerging liquid biopsy technologies and artificial intelligence further demonstrate considerable promise for enhancing noninvasive detection efficacy. Multifaceted collaboration among policymakers, healthcare systems, and communities is essential to implement effective screening programs and ultimately improve survival outcomes.

Background: The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma (HCC). However, tumor regression and progression-free survival (PFS) vary considerably among patients receiving this therapy.

Aim: To identify predictive biomarkers in HCC patients treated with sintilimab (programmed cell death protein-1 inhibitor) plus lenvatinib (tyrosine kinase inhibitor).

Methods: In this single-center study in China, patients with unresectable HCC received sintilimab every 21 days and daily oral lenvatinib. Treatment response was assessed by modified response evaluation criteria in solid tumors. Tumor biopsies underwent RNA sequencing, immune microenvironment profiling, and whole-exome sequencing. Differentially expressed genes (DEGs) and immune cell subsets between response groups were identified, followed by survival analyses. All potential predictors of PFS, together with clinical variables, were included in Cox regression to identify independent prognostic factors.

Results: Between August 2019 and November 2021, 33 patients with hepatitis-B-virus-related HCC were enrolled; by January 2024, 13 had undergone potentially curative surgery or ablation. RNA sequencing identified 94 DEGs between responders (n = 22) and non-responders (n = 11) using Fisher's exact test or Wilcoxon rank-sum test (all P < 0.05). High long intergenic non-protein coding RNA 01554 (LINC01554) and whirlin expression were associated with longer PFS in Kaplan-Meier analysis (P < 0.05). DEG-immune cell analysis showed positive correlations with pro-B and plasma cells in responders, and negative correlations with CD4+ central memory T (Tcm), T helper 1, and natural killer T cells in non-responders; none significantly predicted PFS, although CD4+ Tcm cells approached significance (P < 0.10). Whole-exome sequencing revealed Fanconi anemia complementation group D2 mutations enriched in non-responders (P < 0.05), while cut-like homeobox 1 mutations predicted poorer PFS (P = 0.011). Cox regression identified solitary tumor [P = 0.02, hazard ratio (HR) = 0.31], high LINC01554 (P = 0.01, HR = 0.16), and elevated CD4+ Tcm cells (P = 0.05, HR = 0.29) as independent predictors of prolonged PFS.

Conclusion: Sintilimab plus lenvatinib showed heterogeneous efficacy in HCC. High LINC01554 expression, elevated CD4+ Tcm cells, and solitary tumors may serve as predictive biomarkers for prolonged disease control.

Background: Alcohol can cause alcoholic fatty liver, alcoholic steatohepatitis, alcoholic liver cirrhosis (ALC), and hepatocellular carcinoma. China has become the second-largest country in the world in terms of alcohol consumption, lacking national epidemiological data on alcoholic liver disease (ALD).

Aim: To understand the incidence and characteristics of ALD in Hainan Province of China.

Methods: From October 2022 to April 2023, a stratified proportional multi-stage whole population sampling method was adopted to select permanent residents of Haikou, Sanya, Qionghai, Dongfang, and Wuzhishan in Hainan Province to carry out questionnaire surveys, blood tests, and ultrasound examinations of the liver.

Results: A total of 2704 valid questionnaires were obtained from residents aged 15-93 years old. The rates of drinking, hazardous drinking, and harmful drinking were 31.73%, 14.53%, and 5.03%, respectively. The above rates were higher for males than for females, increasing with income, and the rates for ethnic minorities, such as Li, were higher than for Han Chinese (P < 0.05). Drinking rates increased with literacy (P < 0.05). Drinking rate and hazardous drinking rate decreased with age, were higher for residents of agricultural households than non-agricultural households, and higher for married than unmarried individuals (P < 0.05). The total number of patients with ALD was 142, with a detection rate of 5.25%. ALD detection rate was higher for males than females, decreased with age, and higher with income (P < 0.05). Patients with ALD included 48 (33.8%) cases of mild ALD, 64 (45.1%) cases of alcoholic fatty liver, 18 (12.7%) cases of alcoholic steatohepatitis, and 12 (8.5%) cases of ALC. The proportion of those who consumed more than 80 g of alcohol per day increased as they progressed from mild ALD to ALC stage. Diabetes mellitus and hyperlipidemia were easily combined in some cases, accounting for 25 (17.6%) and 80 (56.3%), respectively. The average daily alcohol consumption of ALD patients of Li ethnicity ≥ 80 g was significantly more than that of Han ethnicity (χ ² = 5.652, P = 0.02), and was predominantly among those who drank large amounts of alcohol intermittently (χ ² = 89.093, P < 0.001).

Conclusion: The rates of drinking, hazardous drinking, harmful drinking, and detection of ALD in Hainan Province need to be paid attention to by advocating a healthy lifestyle, such as abstinence and limiting alcohol consumption.

Gestational diabetes mellitus (GDM) is increasingly recognized not only for its immediate obstetric complications but also for its long-term metabolic consequences in both mothers and their offspring. Traditionally, research has emphasized the roles of pancreatic β-cell dysfunction and placental dysregulation in GDM. However, emerging evidence highlights the maternal liver as a central metabolic hub during pregnancy coordinating glucose, lipid, and hormonal adaptations essential for fetal development. This review synthesizes current findings on how GDM disrupts the maternal liver's adaptive roles, transforming it from a metabolic coordinator into a source of maladaptive endocrine, inflammatory, and nutrient signals. It outlines key mechanistic pathways through which maternal hepatic dysfunction may increase offspring susceptibility to non-alcoholic fatty liver disease and type 2 diabetes mellitus. These include hepatokine dysregulation, altered lipid metabolism, impaired insulin signaling, inflammatory and oxidative stress pathways, and epigenetic and transcriptomic reprogramming. In addition, it explores novel axes such as the gut-liver-placenta interplay, bile acid signaling disruptions, endoplasmic reticulum stress responses, and extracellular vesicle-mediated communication. By reframing the maternal liver's role in GDM pathophysiology, this review identifies critical windows for early clinical intervention and highlights the potential for liver-focused strategies to prevent the intergenerational transmission of metabolic disease.