World J Hepatol [JOURNAL]
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200 papers
Metabolic and hepatic effects of semaglutide and empagliflozin on metabolic dysfunction-associated steatotic liver disease mice.
Niu S, Chen SC, Wang CX … +2 more , Yue L, Wang SQ
World J Hepatol · 2025 Oct · PMID 41179732 · Full text
BACKGROUND: The molecular mechanisms associated with semaglutide and empagliflozin in metabolic dysfunction-associated steatotic liver disease (MASLD) still require further studies to develop precise therapeutic strategi...
BACKGROUND: The molecular mechanisms associated with semaglutide and empagliflozin in metabolic dysfunction-associated steatotic liver disease (MASLD) still require further studies to develop precise therapeutic strategies. AIM: To investigate the effects and the mechanism of action of semaglutide and empagliflozin on MASLD in obese mice. METHODS: The experimental subjects consisted of 32 mice, which were arbitrarily allocated into four distinct groups: (1) The control group; (2) The high-fat group; (3) The Sema group; and (4) The Empa group. Mice were assessed for body weight changes, glycolipid metabolic status, inflammatory oxidative stress levels, pathology and metabolomics. RESULTS: Semaglutide and empagliflozin have been demonstrated to exert a substantial impact on glycolipid reduction, the amelioration of glycolipid metabolism disorders, the attenuation of inflammation and oxidative stress levels, and the restoration of the pathological structure of liver injury to a certain extent in obese mice. No statistically significant differences in the outcomes associated with MASLD were identified between the two cohorts. The results of this study demonstrated that both semaglutide and empagliflozin had the capacity to influence the levels of several lysophosphatidylcholine (LPC). CONCLUSION: It has been hypothesised that the amelioration of MASLD by semaglutide and empagliflozin may be associated with a decrease in the levels of several LPCs in liver tissue.
Quality of life in hereditary haemochromatosis: Scoping review of symptoms and initial ranking of symptoms by a special interest group.
Waqar M, El Asmar ML, Gray D … +3 more , Immanuel A, Shearman J, Ramage JK
World J Hepatol · 2025 Oct · PMID 41179731 · Full text
Haemochromatosis is the most common genetic condition among people of European descent, resulting in iron overload and multi-organ dysfunction. Despite early detection and treatment advances, affected individuals experie...
Haemochromatosis is the most common genetic condition among people of European descent, resulting in iron overload and multi-organ dysfunction. Despite early detection and treatment advances, affected individuals experience significant morbidity impacting their quality of life (QoL). To scope the literature for QoL issues and rank them in order of relevance by professional bodies. A literature search was conducted using PubMed, EMBASE, and MEDLINE in addition to a grey literature search against the eligibility criteria up to July 2023. Inclusion criteria included original articles with data concerning symptoms and QoL in patients with haemochromatosis. Nineteen issues were identified from 47 articles and scored by a haemochromatosis special interest group using a scale of 1 to 10 (10 = highest importance). Mean scores were then calculated for each issue. Fatigue, joint pain and sexual issues were key factors associated with impaired QoL. The least relevant were weight changes and abdominal pain. Other issues raised were anxiety, the development of diabetes, and concerns about genetics and family. This is the first scoping review examining common symptoms affecting QoL of patients with hereditary haemochromatosis. Further studies, including patient interviews and a randomised controlled trial, will inform a validated QoL questionnaire.
Hepatitis B functional cure: Current and future perspective.
Marrapu S, Soni JR, Kamal K … +1 more , Kumar R
World J Hepatol · 2025 Oct · PMID 41179730 · Full text
Chronic hepatitis B (CHB) remains a significant global health challenge, affecting more than 250 million individuals worldwide. A functional cure, defined as the loss of hepatitis B surface antigen (HBsAg) and suppressio...
Chronic hepatitis B (CHB) remains a significant global health challenge, affecting more than 250 million individuals worldwide. A functional cure, defined as the loss of hepatitis B surface antigen (HBsAg) and suppression of hepatitis B virus (HBV) DNA to undetectable levels, represents the optimal therapeutic endpoint for managing CHB. However, the complex pathogenesis of CHB, which includes HBV DNA integration, persistence of covalently closed circular DNA, and impaired immune responses, presents substantial barriers to HBsAg clearance. Current therapies offer limited success in achieving a functional cure, with HBsAg seroclearance occurring in only 3%-5% of patients after 10 years of nucleos(t)ide analogs (NAs) therapy and 8%-14% within 3-5 years of pegylated interferon treatment. To overcome these limitations, novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated. Additionally, immunomodulatory approaches, including therapeutic vaccines and immune checkpoint inhibitors, are being explored to enhance HBV-specific immune responses. The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss, although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring. This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB, discussing its clinical significance, therapeutic challenges, and evolving treatment landscape in the pursuit of a functional cure.
Ultrasound imaging-guided protocol for monitoring tumor growth in orthotopic rat model of hepatocellular carcinoma.
Devan AR, Sasidharan SM, Sreekumar KP … +5 more , Unni AKK, Mangalathillam S, Ansar A, Unni AR, Nath LR
World J Hepatol · 2025 Oct · PMID 41179729 · Full text
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....
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 × 10 N1S1 cells into the left lateral hepatic lobe. Tumor progression was monitored weekly US. Upon reaching 100-150 mm³, an experimental group ( = 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) 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.
Evolution of hepatology practice in Mexico and Latin America: From biochemical markers to genomic medicine.
Panduro A, Roman S, Leal-Mercado L … +2 more , Cardenas-Benitez JP, Mariscal-Martinez IM
World J Hepatol · 2025 Oct · PMID 41179728 · Full text
Genomic medicine has evolved significantly, merging centuries of scientific progress with modern molecular biology and clinical care. It utilizes knowledge of the human genome to enhance disease prevention, diagnosis, tr...
Genomic medicine has evolved significantly, merging centuries of scientific progress with modern molecular biology and clinical care. It utilizes knowledge of the human genome to enhance disease prevention, diagnosis, treatment, and potential reversal. Genomic medicine in hepatology is particularly promising due to the crucial role of the liver in several metabolic processes and its association with diseases such as metabolic dysfunction-associated steatotic liver disease, type 2 diabetes mellitus, liver cirrhosis, and cardiovascular conditions. The mid-20 century witnessed a paradigm shift in medicine, marked by the emergence of molecular biology, which enabled a deeper understanding of gene expression and regulation. This connection between basic science and clinical practice has enhanced our knowledge of the role of gene-environment interactions in the onset and progression of liver diseases. In Latin America, including Mexico, with its genetically diverse and admixed populations, genomic medicine provides a foundation for personalized and culturally relevant health strategies. This review highlights the need for genomic medicine, examining its historical evolution, integration into hepatology in Mexico, and its potential applications in the prevention of chronic diseases. It emphasizes the importance of training in genomic literacy and interdisciplinary education in medical training, particularly in the field of hepatology, with a focus on genomic medicine expertise.
Splenectomy and hepatocellular carcinoma: Cause or confounder?
Kim SH
World J Hepatol · 2025 Oct · PMID 41179727 · Full text
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...
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.
Hepatic hydrothorax as a manifestation of decompensated cirrhosis: An update on current management and future directions.
Cilia BJ, Haridy J, Raj A … +1 more , Hannah N
World J Hepatol · 2025 Oct · PMID 41179726 · Full text
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 i...
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.
Incidence of spontaneous fungal peritonitis in patients with liver cirrhosis in a Mexico City population.
Fajardo-Felix CF, Rodriguez-Negrete EV, Morales-González JA … +1 more , Triana-Romero A
World J Hepatol · 2025 Oct · PMID 41179725 · Full text
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 t...
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 and were isolated, with two of the four patients being positive for ; an SBP incidence of 8.3% was thus calculated. Chronic kidney disease [ = 0.012 and relative risk (RR) = 15] and secondary prophylaxis for SBP ( = 0.049 with RR = 8.6) were statistically significant and associated with a high mortality risk ( = 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.
Improved clinical outcomes following embolization of extrahepatic portosystemic shunts in cirrhotic patients with recurrent hepatic encephalopathy.
Park JW, Kim Y, Lee JS … +3 more , Jung IS, Kim KB, Chae HB
World J Hepatol · 2025 Oct · PMID 41179724 · Full text
BACKGROUND: Hepatic encephalopathy (HE) affects more than 30% of patients with cirrhosis. Extrahepatic portosystemic shunt (EHPSS) has been suggested to be a contributing factor to HE recurrence and mortality. Therefore,...
BACKGROUND: Hepatic encephalopathy (HE) affects more than 30% of patients with cirrhosis. Extrahepatic portosystemic shunt (EHPSS) has been suggested to be a contributing factor to HE recurrence and mortality. Therefore, early detection and intervention in EHPSS may improve patient outcomes. AIM: To evaluate the effects of shunt embolization on mortality and HE recurrence. METHODS: In this retrospective case-control study, 16 cirrhotic patients with HE treated at a tertiary care center from January 2012 to August 2022 were included. Outcomes in eight patients who underwent embolization of EHPSS were compared with those in eight patients receiving standard care without embolization. Data on baseline characteristics, HE recurrence, and overall survival were collected and analyzed using Kaplan-Meier and log-rank tests. RESULTS: Baseline characteristics were comparable between the groups. The 1-year overall survival rate was significantly higher in the treatment group (0.50) than in the control group (0.33). The HE recurrence-free rate was also higher in the treatment group (1.00) than in the control group (0.17). The median survival duration was longer in the treatment group {not reached [95% confidence interval (CI): 23.84 to not available (NA)]} than in the control group [15.02 months (95%CI: 9.86 to NA)] ( = 0.006). Similarly, the recurrence-free duration was longer in the treatment group [63.09 months (95%CI: 63.09 to NA)] than in the control group [9.21 months (95%CI: 4.47 to NA)] ( = 0.006). EHPSS embolization significantly reduced 1-year HE recurrence (hazard ratio = 0.09; 95%CI: 0.01-0.75; = 0.026). CONCLUSION: EHPSS embolization significantly improves 1-year survival and prevents recurrence of HE in cirrhotic patients. Routine computed tomography and early embolization are clinically beneficial.
Clinical significance and pathogenic mechanisms of fatigue in metabolic dysfunction-associated steatotic liver disease.
Sheptulina AF, Golubeva JA, Kiselev AR … +1 more , Drapkina OM
World J Hepatol · 2025 Oct · PMID 41179723 · Full text
Fatigue is among the most common, albeit underestimated, symptoms in patients with metabolic dysfunction-associated steatotic liver disease. It affects quality of life and reduces the effectiveness of non-pharmacological...
Fatigue is among the most common, albeit underestimated, symptoms in patients with metabolic dysfunction-associated steatotic liver disease. It affects quality of life and reduces the effectiveness of non-pharmacological interventions, thereby negatively affecting the prognosis. This review discusses the clinical problems associated with increased fatigue, explores diagnostic methods, considers key pathogenetic mechanisms of this symptom development (including neuroinflammation, hyperammonemia, mitochondrial and muscle dysfunction, sleep disorders, changes in the composition of gut microbiota), and describes the role of interorgan communication (the liver-brain and gut-brain axes) in the formation of the central link of fatigue. The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue, which would include not only the impact on metabolic disorders, but also on neurophysiological and behavioral factors. Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention (which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy) and improve the prognosis of patients with this chronic liver disease.
Acute liver failure caused by alkaloids from traditional Chinese medicine: A case report.
Zhu XY, Zhao YT, Su CS … +3 more , Yuan XD, Zhang SG, Nashan B
World J Hepatol · 2025 Oct · PMID 41179722 · Full text
BACKGROUND: Case reports of traditional Chinese medicine (TCM)-related liver injury have been relatively limited in the past decade. In more than 1200 cases of drug-induced liver injury, TCM accounted for 20.6% of the ca...
BACKGROUND: Case reports of traditional Chinese medicine (TCM)-related liver injury have been relatively limited in the past decade. In more than 1200 cases of drug-induced liver injury, TCM accounted for 20.6% of the cases. Among the chemical components that cause important liver injury, alkaloids (such as chrysanthemum, notoginseng) are typical, mainly causing veno-occlusive disease, and progressing to liver failure in severe cases. Other alkaloids, such as aristolochic acid, have also been associated with liver cancer risk. CASE SUMMARY: In this case report, we present a unique case of a 35-year-old female patient with progressive jaundice within one month after intake of alkaloid-containing TCM, followed by a rapid development of liver injury that progressed to liver failure, and finally, receiving liver transplantation. The clinical diagnosis of TCM-related liver injury is usually an exclusion diagnosis, with a lack of characteristic imaging signs or specific clinical symptoms, resulting in a delay in diagnosis. CONCLUSION: This case shows that the patient received liver transplantation due to progressive liver failure after multiple conservative treatment modalities, thus, with a good prognosis and survival. It provides valuable guidance for the clinical diagnosis of liver injury and the timing of liver transplantation treatment caused by alkaloid hepatotoxic drugs.
Sex-related differences in treatment outcomes of chronic hepatitis C with direct-acting antivirals.
Feyissa GD
World J Hepatol · 2025 Oct · PMID 41179721 · Full text
This editorial provides commentary on the study by Dobrowolska , highlighting the influence of biological sex on hepatitis C virus (HCV) infection risk and disease progression. HCV infection is more common in men; howeve...
This editorial provides commentary on the study by Dobrowolska , highlighting the influence of biological sex on hepatitis C virus (HCV) infection risk and disease progression. HCV infection is more common in men; however, women, regardless of age, show a lower prevalence of genotype 3 infection, diabetes mellitus, and coinfections with hepatitis B virus and human immunodeficiency virus. Women also experience slower liver fibrosis progression. Despite this, mild adverse events, autoimmune diseases, and depression occur more frequently in women. Sustained virologic response at 12 weeks post-treatment was significantly higher in women (98.4%) than in men (96.6%). In women, postmenopausal status, genotype 3 infection, and cirrhosis were independently associated with treatment failure. Early diagnosis and timely antiviral therapy in women are critical to preventing vertical transmission and mitigating disease advancement.
Advancing precision in hepatocellular carcinoma prognostication: The promise of biparametric magnetic resonance imaging-based multimodal models.
Zhou SQ, Ke QH
World J Hepatol · 2025 Oct · PMID 41179720 · Full text
Zuo and Liu investigated the value of a novel noninvasive approach integrating biparametric magnetic resonance imaging, radiomics, deep transfer learning, and clinical factors in predicting Ki-67 risk stratification and...
Zuo and Liu investigated the value of a novel noninvasive approach integrating biparametric magnetic resonance imaging, radiomics, deep transfer learning, and clinical factors in predicting Ki-67 risk stratification and recurrence-free survival (RFS) in hepatocellular carcinoma (HCC). The study included 198 HCC patients and utilized histopathological Ki-67 expression as the reference standard for risk stratification. The integrated multimodal model combining radiomic features, deep transfer learning signatures, and clinical factors (nonsmooth tumor margin and absence of an enhanced capsule), achieved an area under the curve of 0.92 in the training and validation cohorts for predicting high Ki-67 risk, with a sensitivity and specificity of 0.88 and 0.85, respectively. Furthermore, the model effectively stratified RFS, with median RFS of 33.53 months in the high-risk group 66.74 months in the low-risk group, consistent with histopathological findings that directly refer to Ki-67 stratification. The findings highlight the potential of biparametric magnetic resonance imaging-based multimodal models in noninvasive HCC prognostication, though external validation in larger cohorts is warranted. The demand for precise, noninvasive preoperative assessment tools in HCC management remains high in clinical practice.
Nanoparticle-based systems for liver therapy: Overcoming fibrosis and enhancing drug efficacy.
Armillotta MG, Lizzi L, Massimi M
World J Hepatol · 2025 Oct · PMID 41179719 · Full text
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 foll...
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 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.
Effect of empagliflozin on fractional excretion of sodium in patients with cirrhosis and refractory ascites.
Gao Y, Gao YY, Shi RY … +15 more , Ji D, Wang Y, Xu L, Wang Q, Wu MH, You HL, Bu QS, Dong YX, Zhou LZ, Liu W, Song QK, Han Y, Wei H, Zhang XY, Hu ZJ
World J Hepatol · 2025 Oct · PMID 41179718 · Full text
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-transp...
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.
Telerehabilitation for frail cirrhotic patients awaiting liver transplant: A safe, effective strategy to improve outcomes.
Loschi TM, Baccan MDTA, Pereira EC … +3 more , Dellabarba TDLC, Boteon APCS, Boteon YL
World J Hepatol · 2025 Oct · PMID 41179717 · Full text
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-sup...
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 4.03, < 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 ( < 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.
Predicting steroid response in acute alcohol-associated hepatitis: Beyond biomarkers of alcohol consumption.
Zhang JW
World J Hepatol · 2025 Oct · PMID 41179716 · Full text
Acute alcohol-associated hepatitis (AAH) is a life-threatening condition with high mortality, and steroid therapy remains the mainstay of treatment despite variable efficacy. The study by Sabatose explores patient facto...
Acute alcohol-associated hepatitis (AAH) is a life-threatening condition with high mortality, and steroid therapy remains the mainstay of treatment despite variable efficacy. The study by Sabatose explores patient factors distinguishing responders and non-responders to steroid therapy for AAH, focusing on phosphatidylethanol (PEth)-a biomarker of alcohol consumption-and other clinical variables. Their findings indicate that PEth, abstinence duration, and pre-treatment alcohol intake do not predict steroid response, while older age, lower pre-steroid albumin, and higher pre-steroid bilirubin are associated with non-response. Non-responders exhibit higher mortality and healthcare costs, underscoring the need for early identification to guide liver transplantation referrals. This commentary evaluates the implications of these findings-specifically, how prioritizing pre-steroid albumin, bilirubin, and age over alcohol biomarkers can improve clinical decision-making by reducing unnecessary steroid exposure and expediting transplantation referrals for high-risk non-responders-contextualizes them within existing literature, and highlights directions for future research to optimize AAH management.
Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.
Li SQ, Wu JH, Zhou Y … +8 more , Wang CX, Xie L, Liu SY, Su YZ, He W, Chen H, Zhong WW, He YH
World J Hepatol · 2025 Oct · PMID 41179715 · Full text
Metabolic dysfunction-associated steatotic liver disease, characterized by pathological intracellular triglyceride (TG) accumulation, is mechanistically associated with the disrupted spatiotemporal regulation of hepatocy...
Metabolic dysfunction-associated steatotic liver disease, characterized by pathological intracellular triglyceride (TG) accumulation, is mechanistically associated with the disrupted spatiotemporal regulation of hepatocyte nuclear factor (HNF)-dependent transcriptional programs. HNFs, including key members such as HNF-1α, HNF-4α, and HNF-6, constitute a liver-enriched family of transcription factors that govern hepatic lipid metabolism through hierarchical transcriptional regulatory networks. These networks critically regulate the dynamic equilibrium of TG metabolism, encompassing TG synthesis, storage, lipolysis, and lipoprotein-mediated export. This review comprehensively deciphers the molecular cascades through which HNF dysfunction exacerbates TG metabolic disorder in metabolic dysfunction-associated steatotic liver disease. Additionally, we evaluate emerging translational strategies targeting key HNF regulatory nodes and discuss current clinical challenges as well as potential solutions.
Gray zone and the need for expansion in chronic hepatitis B: From theory to clinical practice.
Viet Luong T, Phan Hong Nguyen N, Nguyen TV … +3 more , Tran DH, Dinh Nguyen T, Nguyen Ngoc Dang H
World J Hepatol · 2025 Oct · PMID 41179714 · Full text
Chronic hepatitis B (CHB) remains a significant global health challenge. The natural course of CHB is traditionally divided into four phases: (1) Immune tolerance; (2) Immune activation; (3) Immune control; and (4) Immun...
Chronic hepatitis B (CHB) remains a significant global health challenge. The natural course of CHB is traditionally divided into four phases: (1) Immune tolerance; (2) Immune activation; (3) Immune control; and (4) Immune escape. However, approximately 20%-30% of patients referred to as the "gray zone" (GZ) do not fit neatly into these categories. These patients often exhibit elevated hepatitis B virus DNA levels alongside normal or mildly elevated alanine aminotransferase levels, placing them at significant risk for liver fibrosis, cirrhosis, and hepatocellular carcinoma. However, current clinical guidelines generally do not recommend antiviral therapy for GZ patients, increasing their vulnerability to adverse outcomes. This mini-review explores the challenges and gaps in CHB management, focusing on GZ patients. It also highlights recent advancements in therapeutic strategies and updates in clinical guidelines, emphasizing the need for a more inclusive, risk-adapted approach to treatment. By leveraging novel biomarkers, noninvasive fibrosis assessment tools, and artificial intelligence-driven predictive models, this article advocates for early intervention to mitigate disease progression and improve clinical outcomes in this overlooked population.
Unusual presentation of synchronous double primary gallbladder and hepatic malignancies: A case report.
Zhang K, Liu HL
World J Hepatol · 2025 Oct · PMID 41179713 · Full text
BACKGROUND: Synchronous double primary malignancies of the gallbladder and liver are exceedingly rare clinically and prone to misdiagnosis as metastatic lesions. Due to anatomic contiguity and overlapping imaging charact...
BACKGROUND: Synchronous double primary malignancies of the gallbladder and liver are exceedingly rare clinically and prone to misdiagnosis as metastatic lesions. Due to anatomic contiguity and overlapping imaging characteristics, distinguishing primary carcinomas from metastatic disease is challenging, often delaying curative-intent treatment. Current lack of consensus on management underscores the imperative to investigate their pathologic features and individualized strategies for improved prognostication. CASE SUMMARY: This study presents a rare case of synchronous double primary malignancies involving both gallbladder adenocarcinoma and hepatocellular carcinoma. Following a comprehensive analysis of the patient's diagnostic workup, therapeutic interventions, and 12-month follow-up outcome, the clinicopathological characteristics and prognostic determinants of such synchronous malignancies are described. These findings offer valuable guidance for clinicians in optimizing diagnostic strategies and treatment decision-making for complex presentations of multiple primary cancers. CONCLUSION: The critical insights obtained from this case, integrated with a review of current literature, identify the key diagnostic challenges in differentiating primary metastatic lesions and propose a multidisciplinary management framework.
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