World Journal of Hepatology最新文献

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.

Background: Ascites is the most common complication of cirrhosis. Current pharmacological interventions, such as diuretics, often become ineffective in advanced stages due to diuretic resistance. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated potential in enhancing urinary sodium excretion and mitigating sodium-fluid retention. This study aims to evaluate the effects of SGLT2 inhibitors on the fractional excretion of sodium (FENa) in patients with cirrhotic ascites.

Aim: To determine whether adjunctive therapy with the SGLT2 inhibitor empagliflozin increases FENa compared with standard care alone in patients with cirrhosis and refractory ascites, and to evaluate its short-term safety profile.

Methods: The effect of SGLT2 inhibitor empagliflozin on FENa in patients with cirrhosis and refractory ascites is a multicenter, open-label, randomized controlled trial. A total of 70 patients with refractory ascites secondary to cirrhosis will be enrolled and randomly assigned to receive either empagliflozin 10 mg daily plus standard care or standard care alone for 14 consecutive days. The primary outcome is the change in FENa from baseline to day 14. Secondary outcomes include 24-hour urinary sodium excretion, urine volume, ascites volume (assessed by ultrasound), body weight, and safety indicators. Exploratory outcomes include changes in components of the renin-angiotensin-aldosterone system.

Results: This article reports the study protocol only. No participant data have been collected or analyzed for this manuscript.

Conclusion: This protocol evaluates whether empagliflozin, added to standard therapy, increases sodium excretion and reduces fluid overload in refractory ascites.

The problem of metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a non-infectious pandemic, the growth drivers of which are obesity and diabetes mellitus. According to modern concepts, MASLD develops and progresses as a result of the interaction of multiple genetic, environmental and adaptive factors, which include specific genetic polymorphisms (for example, the patatin-like phospholipase domain-containing protein 3 gene) and epigenetic modifications, dietary patterns (for example, high consumption of saturated fats and fructose), physical inactivity, obesity, insulin resistance, dysregulation of adipokine production, lipotoxicity, oxidative stress, intestinal microbiota dysbiosis (small intestinal bacterial overgrowth syndrome). In addition, due to the high infection rate of Helicobacter pylori (up to 80%) of people in the population, the influence of this factor on the development and progression of MASLD cannot be ruled out. Ye et al presented a study investigating the relationship between Helicobacter pylori infection and metabolic dysfunction associated with hepatic steatosis and identified prognostic factors. Certainly, the work of the Chinese authors deserves attention and further study.

Liver metastases are a leading contributor to cancer-related illness and death, occurring far more frequently than primary liver tumors. Their management remains highly challenging due to the complexity of disease behavior and the need for an individualized, multidisciplinary approach. Effective care increasingly relies on integrating sophisticated diagnostic techniques, advanced systemic and locoregional therapies, and molecularly tailored treatment strategies. This review provides an in-depth analysis of the current clinicopathological perspectives on liver metastases. It explores their epidemiology, mechanisms of spread, histological growth patterns, diagnostic imaging advancements, molecular characteristics, and therapeutic interventions. Additionally, it examines the broader implications for patient quality of life (QoL), healthcare costs, and the particular difficulties associated with managing liver metastases in pediatric patients and individuals with rare malignancies. The article outlines the diverse histopathological features and tumor-liver interface growth patterns, emphasizing their prognostic and therapeutic significance. It evaluates contemporary imaging modalities-including magnetic resonance imaging and computed tomography (CT) with hepatocyte-specific agents, positron emission tomography/CT, and contrast-enhanced ultrasound-and highlights the emerging importance of liquid biopsy and molecular profiling in shaping treatment decisions. The review discusses available treatment options such as chemotherapy, targeted agents, immunotherapies, surgical resection, liver transplantation, and various locoregional therapies. Furthermore, it addresses evolving fields like prognostic scoring systems, radiomics, artificial intelligence (AI) applications, and patient-derived organoid and xenograft models. A summary of current clinical trials and translational research initiatives reflects the fast-paced evolution of this field. The management of liver metastases is rapidly advancing, driven by precision oncology principles and collaborative, multidisciplinary care. The integration of molecular diagnostics, novel therapeutic approaches, and cutting-edge technologies-including AI and organoid-based personalized drug testing-is poised to enhance treatment selection, improve clinical outcomes, and support better QoL. These innovations hold the potential to transform the outlook for patients with liver metastases, moving toward more durable disease control in appropriately selected cases.

Background: In recent years, the number of pediatric patients with unexplained liver disease has been increasing. Whole-exome sequencing (WES) technology has played a significant role in the diagnosis; however, related studies remain limited.

Aim: To investigate the clinical characteristics and genetic causes of unexplained pediatric liver disease to improve the diagnosis and treatment of this disease.

Methods: Eighty children with unexplained liver disease were divided into two groups: The liver enzyme elevation group (Group A) and the cholestasis group (Group B). Children with both elevated liver enzymes and cholestasis were assigned to Group B. The clinical characteristics of the patients were retrospectively summarized, and WES was performed in the patients and their parents.

Results: Genetic results were obtained in 46 patients (46/80, 57.5%), including 38 in Group A (38/65, 58.5%) and 8 in Group B (8/15, 53.3%). A total of 53 pathogenic or likely pathogenic variants were identified in 42 patients (42/80, 52.5%), including 40 previously reported variants and 13 novel variants. Seven variants of uncertain significance were identified in 7 patients (7/80, 8.8%), of which 4 were novel variants. A total of 19 gene mutations were identified: 2 cases of AGL, 15 cases of ATP7B, 1 case of CAPN3, 4 cases of DMD, 1 case of FLG, 1 case of G6PC, 5 cases of JAG1, 2 cases of PHKA2, 2 cases of PYGL, 1 case of SMARCAL1, 1 case of SMPD1, 1 case of TNFAIP3, 1 case of GLB1, and 1 case of MAT1A in Group A; and 1 case of SLC25A13, 3 cases of JAG1, 1 case of ATP8B1, 1 case of ABCC2, 1 case of ABCD3, and 1 case of 45X in Group B.

Conclusion: WES significantly improved the etiological diagnosis of unexplained pediatric liver disease, helping guide individualized treatment and improve prognosis.