World Journal of Hepatology最新文献

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.

While splenectomy has been associated with hepatocellular carcinoma (HCC) in cirrhotic patients, its role as a direct carcinogenic factor remains controversial. This letter argues that the primary risk of HCC stems from the underlying liver disease rather than the surgical removal of the spleen itself. Current literature is based mostly on retrospective analyses lacking randomized controlled trials. Moreover, there is insufficient evidence to suggest that splenectomy in non-cirrhotic patients increases HCC risk. Prospective multicenter studies are needed to clarify the causal relationship.

Background: Telerehabilitation can help overcome geographic barriers and expand access to physical rehabilitation for patients with chronic liver disease.

Aim: To evaluate the impact of adherence to a videoconference-supervised telerehabilitation programme on frailty, functional capacity, and quality of life in pre-frail or frail cirrhotic patients awaiting liver transplantation.

Methods: We conducted a non-randomised controlled clinical trial involving patients listed for liver transplantation from January 2021 to May 2023. Frailty was assessed using the Liver Frailty Index (LFI). Participants were enrolled in a 12-week telerehabilitation programme and classified as adherent (≥ 50% sessions) or non-adherent. Functional capacity was measured using the 4-minute step test (4MST), and quality of life was evaluated with the 36-Item Short Form Health Survey (SF-36) questionnaire.

Results: Fifty-seven pre-frail or frail patients were included in the study and enrolled in the telerehabilitation programme. Adherence was observed in 29.8% of participants. At baseline, non-adherent patients had higher mean LFI scores (4.24 vs 4.03, P < 0.001). Over time, the LFI score increased by 0.11 in non-adherent patients, while adherent patients experienced a mean score reduction of 0.54 (final mean LFI score: 3.2). Adherent patients also demonstrated enhanced heart rate responses in the 4MST (P < 0.001) and greater improvements in the physical functioning, vitality, and mental health domains of the SF-36. No serious adverse events were reported.

Conclusion: The videoconference-supervised telerehabilitation programme was safe and effective in reducing frailty and improving functional outcomes and quality of life in adherent cirrhotic patients on the liver transplant waitlist.

Liver diseases are among the most insidious and life-threatening conditions due to their progressive nature and late symptom onset. Cirrhosis and hepatocellular carcinoma account for most liver-related deaths, often following the progression from fibrosis. Fibrosis creates a hostile microenvironment, characterized by portal hypertension, vascular capillarization, intrahepatic vasoconstriction, and extracellular matrix deposition, which severely limits drug efficacy. Advances in pharmaceutical science have prompted efforts to develop liver-targeted drug delivery systems to prevent or reduce the progression of fibrosis, a central feature of many liver diseases. Fibrosis often reduces the in vivo efficacy of both approved and experimental drugs, underscoring the need for improved delivery strategies focused on stability, controlled release, and precise targeting. Nanoparticle (NP)-based systems show promise, either by delivering therapeutic agents, or in some cases, by contributing directly to the therapeutic effects. This review summarizes the main types of NPs explored for liver disease treatment, especially those aiming to reverse fibrosis or prevent its progression, a critical therapeutic target in chronic liver diseases. Additionally, it examines gene delivery and ultrasound-guided microbubble strategies, which can be combined with NPs to improve cell-specific targeting and boost therapeutic effects. Together, these approaches have the potential to address current therapeutic challenges and accelerate the development of liver-targeted treatments for clinical application.

Hepatic hydrothorax (HH) is an uncommon yet severe manifestation of portal hypertension which develops in 5%-10% of patients with liver cirrhosis. It typically presents as a unilateral, right-sided pleural effusion and in the context of end-stage liver disease and concomitant ascites. The most widely accepted explanatory model for HH accumulation is the formation of small diaphragmatic defects (pleuroperitoneal connections) facilitating migration of ascitic fluid from the peritoneal cavity directly to the pleural cavity. Medical management involves sodium restriction and diuretic therapy, with thoracentesis also offering symptomatic relief. In cases of refractory HH, a transjugular intrahepatic portosystemic shunt is considered either as definitive treatment or as a bridge to liver transplantation, which remains the only curative treatment option. HH refractory to medical therapy presents a challenging clinical dilemma, particularly in those who are ineligible for liver transplantation. In this mini-review, we aim to highlight the pathophysiology, clinical presentation, diagnosis and management of HH. Additionally, we discuss and appraise novel therapeutic options and offer future directions.

Background: Individuals with liver cirrhosis (LC) are likely to experience multiple infectious processes due to the immune dysfunction caused by the disease. Our hypothesis is that this group of patients is predisposed to fungal infections. To date, the incidence of spontaneous fungal peritonitis (SFP) has not been determined in Mexico; this endeavor is of great importance because many patients may be suffering from this condition without receiving targeted treatment, which may increase mortality.

Aim: To report the incidence of SFP in patients presenting with decompensated LC with ascites.

Methods: This was a prospective, single-center, descriptive, observational and cross-sectional study where patients presenting with decompensated LC with ascites were evaluated from November 2023 to May 2024 in Mexico City. Fungal cultures of ascites were performed and the samples kept in an incubator for 10 days to 14 days, and molecular tests (the API 20 C AUX test) were used for molecular characterization.

Results: Of the 48 patients included, 54.2% were women, 77.1% had a comorbidity, 47.9% had LC secondary to metabolic dysfunction, 43.8% were classified as Child-Pugh C with a model for end-stage liver disease 3.0 median score of 22, and 10.4% were in secondary prophylaxis for spontaneous bacterial peritonitis (SBP). Only four patients had positive cultures where Candida parapsilosis and Candida albicans were isolated, with two of the four patients being positive for Rhodotorula minuta; an SBP incidence of 8.3% was thus calculated. Chronic kidney disease [P = 0.012 and relative risk (RR) = 15] and secondary prophylaxis for SBP (P = 0.049 with RR = 8.6) were statistically significant and associated with a high mortality risk (P = 0.001 with RR = 33).

Conclusion: The presence of infection of fungal origin in ascites in patients presenting with cirrhosis increases short- and medium-term mortality; therefore, it is recommended that fungal culture tests are performed in those patients who visit the emergency room or experience continuous admission with acute decompensation and no bacteria identified in ascites cultures, and even more so in patients with chronic kidney disease and a history of antibiotic use as prophylaxis for SBP. Further studies are needed for the identification of clinical and biochemical data that can help to define SFP so that its presence may be assessed without the need to wait for a positive fungal culture. Thus, treatment may be initiated early in the hope of having a positive impact on the prognosis in this group of patients.

Background: Syngeneic orthotopic tumor models offer an optimal functional tumor-immune interface for hepatocellular carcinoma research. Yet, unpredictable growth kinetics and spontaneous regression pose major obstacles. Efficient induction protocols and continuous monitoring are therefore essential. Routine exploratory surgeries are ethically untenable, making non-invasive imaging modalities attractive alternatives. High-resolution magnetic resonance imaging and microcomputed tomography deliver detailed insights but incur substantial equipment costs, radiation risks, time demands, and require specialized expertise-challenges that limit their routine use. In contrast, ultrasound (US) imaging emerges as a cost-effective, radiation-free, and rapid approach, facilitating practical and ethical longitudinal assessment of tumor progression in preclinical studies.

Aim: To optimize the orthotopic hepatocellular carcinoma model and evaluate the potential of US imaging for accurate and cost-effective tumor monitoring.

Methods: Hepatocellular carcinoma was induced in 28 Sprague Dawley rats by implanting 5 × 10⁶ N1S1 cells into the left lateral hepatic lobe. Tumor progression was monitored weekly via US. Upon reaching 100-150 mm³, an experimental group (n = 14) received Sorafenib (40 mg/kg) orally on alternate days for 28 days; efficacy was compared to untreated controls. US accuracy was validated against micro-computed tomography, gross caliper measurements and histopathological analysis. Reliability and operator proficiency in US assessment were also evaluated.

Results: US images procured 7-day post-surgery revealed a well-defined hypoechoic nodule at the left liver lobe tip, confirming successful tumor induction (mean volume 130 ± 39 mm³). Only three animals exhibited spontaneous regression by week 2, underscoring the model's stability. Sorafenib treatment elicited a marked tumor reduction (678 ± 103 mm³) vs untreated control (6005 ± 1760 mm³). US assessment demonstrated robust intra and interobserver reproducibility with high sensitivity and specificity for tumor detection. Moreover, US derived volumes correlated strongly with gross caliper measurements, histopathological analysis, and microcomputed tomography imaging, validating its reliability as a non-invasive monitoring tool in preclinical hepatocellular carcinoma studies.

Conclusion: The results demonstrate that US imaging is a reliable, cost-effective, and animal sparing approach with an easy to-master protocol, enabling monitoring of tumor progression and therapeutic response in orthotopic liver tumor models.