World J Hepatol [JOURNAL]
Sun
200 papers
Gender disparities in hepatitis C treatment: A call for tailored approaches.
Gadour E
World J Hepatol · 2025 Sep · PMID 41024873 · Full text
Considering the recent study by Dobrowolska , which investigated sex-related differences in treatment outcomes for chronic hepatitis C infection, this letter endorses the findings that highlight significant disparities b...
Considering the recent study by Dobrowolska , which investigated sex-related differences in treatment outcomes for chronic hepatitis C infection, this letter endorses the findings that highlight significant disparities between male and female patients. The study revealed that women, particularly those in the premenopausal and menopausal stages, exhibited higher sustained virologic response rates than men. However, postmenopausal women encounter unique challenges that merit attention. This letter emphasizes the necessity for healthcare providers to implement sex-sensitive approaches in the management of hepatitis C, acknowledging the impact of biological, hormonal, and psychosocial factors on treatment efficacy. By advocating tailored treatment strategies that address these disparities, we can improve patient outcomes and ensure equitable healthcare for all individuals affected by hepatitis C. Furthermore, this letter calls for additional research to explore the underlying mechanisms driving these differences, ultimately contributing to more effective and personalized care of patients across diverse demographics.
Rapamycin nanoparticles suppress autoreactive lymphocytes and reduce anti-mitochondrial antibodies in primary biliary cholangitis: Mechanisms and implications.
Bhatnagar P, Eid N
World J Hepatol · 2025 Sep · PMID 41024872 · Full text
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts, primarily by infiltrating lymphocytes, and has limited therapeutic options. A growin...
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts, primarily by infiltrating lymphocytes, and has limited therapeutic options. A growing body of evidence suggests that nanoparticles encapsulating rapamycin (ImmTOR) can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases. In a recent study, Yang investigated the therapeutic effects of ImmTOR in a mouse model of PBC. ImmTOR treatment reduced the expression and number of CD4+ T cells, CD8+ T cells, and B cells isolated from the liver and spleen, improved liver inflammation and enzyme levels, and was associated with a concomitant decrease in anti-mitochondrial antibody levels. In this editorial, we highlight the significance of these findings, focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels, ultimately improving liver pathology, through pathways such as mammalian target of rapamycin inhibition and autophagy restoration. We also offer a perspective on future research directions for PBC in both animal models and studies.
Albumin-bilirubin score reflects the extent of liver fibrosis in chronic hepatitis C patients treated with direct-acting antivirals.
Ewid M, Sherif H, Saquib N … +6 more , Alammari AM, Ismail AAM, Alkahlot MH, Ahmed ZT, Al-Zabidi FZM, Al Mutiri N
World J Hepatol · 2025 Sep · PMID 41024871 · Full text
BACKGROUND: The albumin-bilirubin (ALBI) score was developed as a prognostic tool for patients with hepatocellular carcinoma. However, its new role as an indicator of liver fibrosis in chronic hepatitis C virus (HCV) pat...
BACKGROUND: The albumin-bilirubin (ALBI) score was developed as a prognostic tool for patients with hepatocellular carcinoma. However, its new role as an indicator of liver fibrosis in chronic hepatitis C virus (HCV) patients is under investigation. AIM: To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients. METHODS: We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah, Saudi Arabia. Demographic/clinical data, liver function tests, non-invasive tests for liver fibrosis, and ALBI score/grades were evaluated before and two years after direct-acting antivirals (DAA) treatment. RESULTS: The median ALBI score improved from -2.51 to -2.62 after DAA treatment ( < 0.05). Additionally, the ALBI score improved irrespective of the level of fibrosis, with improvement more evident in patients with advanced fibrosis (-2.26 to -2.41, < 0.05). The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis (aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, and fibrosis-4 index) at baseline and after DAA treatment ( < 0.05). Moreover, the receiver operating characteristic curve demonstrated ALBI score's ability to predict advanced fibrosis (F3, F4) [area under the curve = 0.76, (95% confidence interval: 0.70-0.81), < 0.001, best cut-off value = -2.38 (sensitivity 60% and specificity 83%)]. CONCLUSION: The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA treatment.
Explant-based prognostic models for hepatocellular carcinoma recurrence after liver transplantation: A systematic review and meta-analysis.
Christofoli de Barros I, Vanzin Fernandes M, Rodríguez Villafuerte S … +1 more , Brandão ABM
World J Hepatol · 2025 Sep · PMID 41024870 · Full text
BACKGROUND: Liver transplantation (LT) is the preferred curative treatment for early-stage hepatocellular carcinoma (HCC). However, approximately 17% of patients experience post-transplant recurrence. Extrahepatic recurr...
BACKGROUND: Liver transplantation (LT) is the preferred curative treatment for early-stage hepatocellular carcinoma (HCC). However, approximately 17% of patients experience post-transplant recurrence. Extrahepatic recurrence and early recurrence (within one year after LT) are associated with poorer post-recurrence survival. AIM: To assess which explant-based prognostic model best predicts HCC recurrence after LT. METHODS: A systematic search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to January 30, 2025. Nine retrospective studies comprising 5348 patients were included. Three explant-based prognostic models were analyzed: (1) Risk estimation of tumor recurrence after transplant (RETREAT); (2) Decaens; and (3) Predicting Cancer Recurrence Score (PCRS). Primary outcomes included: (1) HCC recurrence rate; and (2) Predictive accuracy of each score over a five-year follow-up. RESULTS: All studies were retrospective and included validation cohorts from North America, Europe, and Asia. The overall recurrence rate was 7%. For high-risk thresholds, pooled sensitivity and specificity were Risk Estimation of Tumor Recurrence after Transplant (RETREAT) ≥ 5 (0.381/0.953), Decaens ≥ 4 (0.676/0.817), and PCRS ≥ 3 (0.217/0.987). Among high-risk patients, recurrence reached 45% (95%CI: 35.1-57.0). Area under the curve comparisons showed no statistically significant differences among models. Thus, no model demonstrated clear superiority. CONCLUSION: Although several explant-based models exist, their limited sensitivity suggests that many patients at risk of recurrence remain unidentified. The RETREAT score, developed in a large cohort, remains the most extensively validated. Future approaches should focus on developing improved prognostic tools using larger, preferably prospective datasets, and integrating artificial intelligence to enhance risk stratification and post-transplant surveillance.
Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches.
Zeng T, Huang SY, Chen JN … +3 more , Pang JH, Chong YT, Li XH
World J Hepatol · 2025 Sep · PMID 41024869 · Full text
Porphyria refers to a group of rare inherited metabolic disorders caused by enzymatic deficiencies in the heme biosynthesis pathway. These deficiencies lead to the pathological accumulation of neurotoxic porphyrin precur...
Porphyria refers to a group of rare inherited metabolic disorders caused by enzymatic deficiencies in the heme biosynthesis pathway. These deficiencies lead to the pathological accumulation of neurotoxic porphyrin precursors, resulting in multisystem damage. Currently, there are no curative therapeutic interventions, and patients frequently experience severe morbidity or life-threatening complications. Among the most critical manifestations is protoporphyric liver disease, in which hepatotoxic porphyrins and their precursors drive progressive hepatic injury and cholestasis. Persistent elevation of these metabolites can lead to irreversible parenchymal damage, significantly affecting both quality of life and long-term prognosis. The clinical presentation of porphyria-associated liver injury is highly variable and often has an insidious onset. However, a subset of patients may experience rapid progression to acute liver failure or fulminant hepatic dysfunction. Diagnosis is based on clinical evaluation and is confirmed by genetic testing. Current treatment strategies are focused on symptom management while underlying disease mechanisms remain unaddressed, posing significant therapeutic challenges. This review summarizes the pathophysiology, clinical manifestations, and diagnostic approaches for porphyria-associated liver injury, highlighting emerging therapies with the potential to improve patient outcomes.
From gut to liver: Exploring the relationship between inflammatory bowel disease and metabolic dysfunction-associated steatotic liver disease.
Lopes MA, Oliveira ECS, Quaglio AEV … +8 more , Santos A, Imbrizi M, Mendes LER, Beraldo RF, Baima JP, Spiller AL, Magro DO, Sassaki LY
World J Hepatol · 2025 Sep · PMID 41024868 · Full text
Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic condition marked by relapsing inflammation of the gastrointestinal tract. Metabolic dysfunction-associated steatotic liver...
Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic condition marked by relapsing inflammation of the gastrointestinal tract. Metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes the interplay between metabolic alterations and modern lifestyle factors in its pathogenesis. Emerging evidence suggests that individuals with IBD are at increased risk for MASLD, driven by shared mechanisms, including gut dysbiosis, chronic systemic inflammation, and compromised intestinal barrier function. However, MASLD frequently remains underdiagnosed in this population. The gut microbiota plays a central role in modulating these interactions, influencing both intestinal permeability and metabolic regulation. Key pathophysiological mechanisms include alterations in short-chain fatty acid production, particularly reduced butyrate synthesis; disruption of bile acid signaling pathways farnesoid X receptor and Takeda G protein-coupled receptor 5 receptors; and activation of pro-inflammatory cascades through toll-like receptor 4 in the liver. These events lead to increased intestinal permeability, translocation of microbial products, and amplification of hepatic inflammation. This review synthesizes current knowledge on the shared pathophysiological pathways linking IBD and MASLD-focusing on dysbiosis, barrier dysfunction, and inflammation-and underscores their clinical relevance. Understanding the gut-liver axis provides opportunities for early diagnosis and integrated management strategies, aiming to reduce disease burden and improve patient outcomes.
Noninvasive prediction of clinically significant portal hypertension in metabolic dysfunction-associated steatotic liver disease compared to other chronic liver diseases.
Masood M, Thandassery RB
World J Hepatol · 2025 Sep · PMID 41024867 · Full text
Liver biopsy is rarely performed for the diagnosis of compensated advanced chronic liver disease (cACLD) in the current clinical hepatology practice. In the early stage, cACLD presents without portal hypertension, and in...
Liver biopsy is rarely performed for the diagnosis of compensated advanced chronic liver disease (cACLD) in the current clinical hepatology practice. In the early stage, cACLD presents without portal hypertension, and in the later stage, it presents with portal hypertension. Hepatic venous pressure gradient measurement is the gold standard for diagnosing portal hypertension, but it is rarely used due to its invasive nature. The recent Baveno VII consensus recommends a noninvasive strategy for the diagnosis of cACLD and clinically significant portal hypertension (CSPH). However, there is some uncertainty regarding the diagnostic accuracy of Baveno VII criteria for predicting CSPH among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This is pertinent as MASLD has become the most important cause of cACLD in the United States. This mini-review outlines the diagnostic performance of Baveno VII criteria and other noninvasive criteria for predicting CSPH in patients with cACLD from MASLD compared to non-MASLD causes.
Nutrients as epigenetic modulators in metabolic dysfunction-associated steatotic liver disease.
Rodriguez S, Dahlem MLF, Rossoni C … +3 more , Marroni NP, Marroni CA, Fernandes SA
World J Hepatol · 2025 Aug · PMID 40901607 · Full text
To improve understanding of the multifaceted nature of metabolic dysfunction-associated steatotic liver disease (MASLD), the American Association for the Study of Liver Diseases, in collaboration with the European Associ...
To improve understanding of the multifaceted nature of metabolic dysfunction-associated steatotic liver disease (MASLD), the American Association for the Study of Liver Diseases, in collaboration with the European Association for the Study of the Liver and the Latin American Association for the Study of the Liver, proposed a broader and more flexible definition, highlighting the role of underlying metabolic dysfunction. MASLD represents the most common chronic liver disease worldwide; however, the impact of the disease goes beyond its epidemiological aspects. Currently, the impact on patients and healthcare systems, due to hepatic and extrahepatic complications, is significant. Recent evidence has demonstrated that epigenetic regulation plays a key role in the development and progression of MASLD. This highly sophisticated regulatory system includes DNA methylation, histone modification, chromatin remodeling, and modulation of non-coding RNA, without causing changes in the primary DNA sequence. Diet, particularly the Westernized diet (characterized by high levels of processed foods, fats, and sugars, but deficient in vitamins and minerals), contributes to the pathogenesis of MASLD through epigenetic modulation at multiple levels. Given the association between diet, epigenetics, and MASLD, this review aims to present some micronutrients and their importance in the prevention and/or treatment of metabolically dysfunction-associated steatotic liver disease.
Exploring the interplay between metabolic dysfunction-associated fatty liver disease and gut dysbiosis: Pathophysiology, clinical implications, and emerging therapies.
Al-Busafi SA, Alwassief A, Madian A … +4 more , Atalla H, Alboraie M, Elbahrawy A, Eslam M
World J Hepatol · 2025 Aug · PMID 40901606 · Full text
Metabolic dysfunction-associated fatty liver disease (MAFLD) now affects roughly one-quarter of the world's population, reflecting the global spread of obesity and insulin resistance. Reframing non-alcoholic fatty liver...
Metabolic dysfunction-associated fatty liver disease (MAFLD) now affects roughly one-quarter of the world's population, reflecting the global spread of obesity and insulin resistance. Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis, where intestinal dysbiosis acts as a key driver of hepatic injury. Altered microbial communities disrupt epithelial integrity, promote bacterial translocation, and trigger endotoxin-mediated inflammation that accelerates steatosis, lipotoxicity, and fibrogenesis. Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis, amplifying cardiometabolic risk. Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts, linked to diet quality, sedentary behavior, adiposity, and host genetics. Newly developed microbiome-derived biomarkers, advanced elastography, and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification, although external validation remains limited. In early trials, interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics, rational diet patterns, next-generation fecal microbiota transplantation, and bile-acid-modulating drugs show encouraging histological and metabolic gains. Optimal care will likely couple these tools with weight-centered lifestyle programmes in a precision-medicine framework. Key challenges include inter-ethnic variability in microbiome signatures, the absence of consensus treatment algorithms, and regulatory barriers to live biotherapeutics. Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.
Biparametric magnetic resonance imaging-based radiomic and deep learning models for predicting Ki-67 risk stratification in hepatocellular carcinoma.
Zuo XY, Liu HF
World J Hepatol · 2025 Aug · PMID 40901605 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent and life-threatening cancer with increasing incidence worldwide. High Ki-67 risk stratification is closely associated with higher recurrence rates and worse outco...
BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent and life-threatening cancer with increasing incidence worldwide. High Ki-67 risk stratification is closely associated with higher recurrence rates and worse outcomes following curative therapies in patients with HCC. However, the performance of radiomic and deep transfer learning (DTL) models derived from biparametric magnetic resonance imaging (bpMRI) in predicting Ki-67 risk stratification and recurrence-free survival (RFS) in patients with HCC remains limited. AIM: To develop a nomogram model integrating bpMRI-based radiomic and DTL signatures for predicting Ki-67 risk stratification and RFS in patients with HCC. METHODS: This study included 198 patients with histopathologically confirmed HCC who underwent preoperative bpMRI. Ki-67 risk stratification was categorized as high (> 20%) or low (≤ 20%) according to immunohistochemical staining. Radiomic and DTL signatures were extracted from the T2-weighted and arterial-phase images and combined through a random forest algorithm to establish radiomic and DTL models, respectively. Multivariate regression analysis identified clinical risk factors for high Ki-67 risk stratification, and a predictive nomogram model was developed. RESULTS: A nonsmooth margin and the absence of an enhanced capsule were independent factors for high Ki-67 risk stratification. The area under the curve (AUC) of the clinical model was 0.77, while those of the radiomic and DTL models were 0.81 and 0.87, respectively, for the prediction of high Ki-67 risk stratification, and the nomogram model achieved a better AUC of 0.92. The median RFS times for patients with high and low Ki-67 risk stratification were 33.00 months and 66.73 months, respectively ( < 0.001). Additionally, patients who were predicted to have high Ki-67 risk stratification by the nomogram model had a lower median RFS than those who were predicted to have low Ki-67 risk stratification (33.53 66.74 months, = 0.007). CONCLUSION: Our developed nomogram model demonstrated good performance in predicting Ki-67 risk stratification and predicting survival outcomes in patients with HCC.
Toxins to treatments: Impact of environmental pollutants, gut microbiota, and natural compounds on non-alcoholic fatty liver disease progression.
Sharma T, Kaushal N, Garla R
World J Hepatol · 2025 Aug · PMID 40901604 · Full text
Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing global contributor to the disease burden associated with the consequences of chronic liver disease, including cirrhosis and liver cancer. It is projected t...
Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing global contributor to the disease burden associated with the consequences of chronic liver disease, including cirrhosis and liver cancer. It is projected that more than fifty percent of the adult population, including women, smokers, and individuals without metabolic syndrome, will have NAFLD by 2040. Various mechanisms linking the gut microbiome to NAFLD and the consequent fibrosis have been discerned, which suggest the dysbiosis-induced impairment of gut endothelial barrier function, leading to hepatic inflammation through the translocation of bacterial components. NAFLD is progressively associated with environmental variables, especially exposure to heavy metals that impair liver metabolism, produce oxidative stress, and exacerbate inflammation, hence accelerating its progression. These toxicants also modify the composition of gut microbiota, hence intensifying liver damage. Comprehending the processes by which heavy metals contribute to NAFLD is essential for formulating tailored therapies. This review examines strategies to alleviate liver toxicity caused by heavy metals, including chelation therapy, dietary modifications (antioxidants and hepatoprotective nutrients), gut microbiome modulation probiotics and postbiotics like short-chain fatty acids to restore intestinal barrier function and use of essential minerals like selenium, with potent antioxidant characteristics. Employing these measures may offer an integrated approach for addressing NAFLD in individuals subjected to heavy metal poisoning.
Patient factors in responders and non-responders treated with steroids for acute alcohol-associated hepatitis.
Sabatose KW, Baker A, Kugler K … +9 more , Delikat J, Jowers B, Kumar A, Aslam S, Buggs J, Machado-Denis C, Kemmer N, Dhanireddy K, Syed R
World J Hepatol · 2025 Aug · PMID 40901603 · Full text
BACKGROUND: Steroids remain the primary treatment for severe alcohol-associated hepatitis (AAH), though there is little available tools to predict patient response to steroids. It was hypothesized that phosphatidylethano...
BACKGROUND: Steroids remain the primary treatment for severe alcohol-associated hepatitis (AAH), though there is little available tools to predict patient response to steroids. It was hypothesized that phosphatidylethanol (PEth) value will inversely correlate with response to steroid therapy based on Lille score in AAH. AIM: To assess the relationship of patient factors, focusing on pre-steroid therapy PEth value, to steroid therapy response in AAH. METHODS: A retrospective case control study was performed on patients who received ≥ 4 days of steroid therapy for AAH at our hospital between July 1, 2019 and June 30, 2022. A total of 2087 patients were screened for AAH and those treated with steroids were included for statistical analysis utilizing independent sample -test and for categorical variables using the test. RESULTS: No correlation was found between PEth value, pre-steroids abstinence length, or number of drinks per week pre-steroids and response to steroids. Non-responder status significantly correlated with older age ( = 0.024), lower albumin ( = 0.003), and higher bilirubin ( = 0.010) pre-steroids. Our study suggests that age, pre-steroid albumin, and pre-steroid bilirubin levels may predict nonresponse to steroid therapy. Non-responders have increased incidence of death and higher medical costs. CONCLUSION: Identifying non-responders through these identified factors should prompt early referral for liver transplantation. Future prospective studies with larger population size are needed to assess the efficacy of combined pre-steroid age, albumin, bilirubin and other biochemical markers as predictors of steroid response.
Metabolic and immune links between sarcopenia and liver disease.
Kotlyarov SN
World J Hepatol · 2025 Aug · PMID 40901602 · Full text
Skeletal muscles perform important metabolic functions. Muscle mass wasting in sarcopenia is an urgent problem of modern medicine, the interest in which is related to its prognostic significance. The liver has numerous d...
Skeletal muscles perform important metabolic functions. Muscle mass wasting in sarcopenia is an urgent problem of modern medicine, the interest in which is related to its prognostic significance. The liver has numerous direct and indirect metabolic and immune connections with skeletal muscle and disruptions of these connections in liver disease are of clinical interest. A recent article by Liang emphasized potential biomarkers of sarcopenia in liver cirrhosis. Identification of biomarkers of sarcopenia in patients with cirrhosis has important diagnostic value. Common pathophysiologic mechanisms of sarcopenia and liver cirrhosis include disorders of protein and energy metabolism, disturbances in the structure of gut microbiota, inflammation and oxidative stress.
Sex differences in severity, outcomes, and healthcare utilization in alcohol-associated hepatitis.
Harris E, Rhudy C, Roy L … +2 more , Cloud A, Leyson CD
World J Hepatol · 2025 Aug · PMID 40901601 · Full text
BACKGROUND: There is increasing incidence of alcohol-associated liver disease in females. Despite this recent increased incidence, there is a paucity of research on the clinical course and outcomes of alcohol-associated...
BACKGROUND: There is increasing incidence of alcohol-associated liver disease in females. Despite this recent increased incidence, there is a paucity of research on the clinical course and outcomes of alcohol-associated hepatitis (AH) in females compared to males. AIM: To assess if there may be sex differences in severity, outcomes, and healthcare utilization for patients hospitalized for AH. METHODS: This study used ICD-9-CM and ICD-10-CM codes to retrospectively identify inpatient encounters for AH at the University of Kentucky from 2012-2021 and obtained data on patient demographics and clinical outcomes. Encounters were cohorted by patient sex and differences in patient demographics and clinical outcomes were assessed. Multivariate logistic regression models were constructed to assess risk of mortality, sepsis, and mechanical ventilation during the encounter. RESULTS: Of 1386 subjects, 511 (36.9%) were female and 875 (63.1%) were male. Both sexes had similar baseline characteristics of race/ethnicity, discriminant function score, model of end-stage liver disease score, and length of hospital stay. However, the incidence of urinary tract infection, sepsis, and norepinephrine administration was significantly higher for females. Males had a significantly higher incidence of esophageal variceal bleed. On multivariate logistic regression analysis, females had higher odds of encounter sepsis (OR 1.41; 95%CI: 1.064-1.869) and mechanical ventilation (OR 1.352; 95%CI: 1.006-1.816). Odds of encounter mortality were significantly increased in encounters with sepsis (OR 2.309; 95%CI: 1.419-3.757) and mechanical ventilation (OR 9.301; 95%CI: 5.724-15.114). CONCLUSION: This study shows sex-based differences in AH outcomes at the University of Kentucky. Future studies are warranted to assess whether tailoring treatments will improve clinical outcomes in females with AH.
Myths and facts about the role of diet in metabolic dysfunction-associated steatotic liver disease.
Fernandes SA
World J Hepatol · 2025 Aug · PMID 40901600 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of liver-related morbidity worldwide. Despite broad consensus on the importance of diet in managing the disease, numerous myths...
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of liver-related morbidity worldwide. Despite broad consensus on the importance of diet in managing the disease, numerous myths and misconceptions persist among patients, healthcare professionals, and the general public. This article aims to critically review the main myths and facts surrounding the role of diet in MASLD, in light of the most current scientific evidence.
Bile acids in metabolic dysfunction-associated steatotic liver disease.
Zerem E, Kunosic S, Kurtcehajic A … +2 more , Zerem D, Zerem O
World J Hepatol · 2025 Aug · PMID 40901599 · Full text
The liver is a central metabolic organ that regulates numerous physiological processes, including glucose and lipid metabolism, detoxification, and the synthesis of essential proteins and bile. Bile acids (BAs), synthesi...
The liver is a central metabolic organ that regulates numerous physiological processes, including glucose and lipid metabolism, detoxification, and the synthesis of essential proteins and bile. Bile acids (BAs), synthesized from cholesterol in hepatocytes, not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally, closely linked with obesity, insulin resistance, and other components of metabolic syndrome. In MASLD, the metabolism of BAs is markedly disrupted, resulting in alterations in their synthesis, composition, and signaling activity. These changes contribute to hepatic steatosis, inflammation, and fibrosis, thereby exacerbating metabolic dysfunction and liver damage. The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity, but also as active mediators of its pathogenesis. Modulators of BA signaling pathways, especially FXR agonists, are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD. Recent research has yielded promising results, indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function. This minireview outlines the physiological roles of BAs, seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression, and highlights current and emerging therapeutic approaches. A deeper understanding of these complex interactions is essential for improving the diagnosis, prognosis and treatment of MASLD.
Modern approach to hepatocellular carcinoma treatment.
Cortese F, Anagnostopoulos F, Bazzocchi MV … +9 more , Caringi S, Pisani AR, Renzulli M, Paraskevopoulos I, Laera L, Surgo A, Spiliopoulos S, Memeo R, Inchingolo R
World J Hepatol · 2025 Aug · PMID 40901598 · Full text
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, necessitating innovative treatment strategies. Surgical resection and liver transplantation continue to be the gold standards...
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, necessitating innovative treatment strategies. Surgical resection and liver transplantation continue to be the gold standards for early-stage HCC; however, advances in imaging and minimally invasive techniques have improved patient selection and outcomes. Additionally, the emergence of targeted therapies and immunotherapy has transformed the treatment landscape for advanced HCC. This review highlights the efficacy of agents such as tyrosine kinase inhibitors, alongside emerging options like immune checkpoint inhibitors, which have shown promise in clinical trials. Furthermore, the role of locoregional therapies, including ablation in the setting of combined treatment, transarterial chemoembolization and transarterial radioembolization with flow catheters, cone-beam computed tomography and 4D navigation guidance, is examined in the context of bridging therapies for patients awaiting surgical intervention. The integration of multidisciplinary care approaches and personalized treatment plans is crucial for optimizing outcomes. Future directions for HCC treatment are discussed, including the potential of novel biomarkers in prognosis and treatment response. This comprehensive overview aims to equip clinicians with the latest insights and foster collaborative efforts to improve HCC patient management and survival rates.
Advances in portal pressure measurement: Endoscopic techniques, challenges, and implications for liver transplantation.
Singla N, Shantan V, Saraswat A … +1 more , Singh AP
World J Hepatol · 2025 Aug · PMID 40901597 · Full text
Portal hypertension is a critical determinant of prognosis in chronic liver disease and a key factor in evaluating candidates for liver transplantation. Traditional methods such as hepatic venous pressure gradient (HVPG)...
Portal hypertension is a critical determinant of prognosis in chronic liver disease and a key factor in evaluating candidates for liver transplantation. Traditional methods such as hepatic venous pressure gradient (HVPG) measurement have long been considered the gold standard for assessing portal pressure. However, these methods are invasive and carry procedural limitations. Recent advances in endoscopic ultrasound (EUS)-guided techniques have emerged as promising alternatives, offering direct and minimally invasive assessment of portal pressure. EUS-guided portal pressure gradient measurement enables real-time evaluation of haemodynamic through direct access to the portal system. This technique has shown to be as accurate as HVPG, and it has some extra benefits, like the ability to take liver biopsies and check collateral circulation all at the same time. Despite these benefits, the technique poses challenges such as operator dependence, procedural complexity, and limited standardization across centres. This minireview highlights the evolution of portal pressure measurement, focusing on the potential of EUS-guided techniques in pre-transplant assessment, risk stratification, and monitoring therapeutic outcomes. Furthermore, it discusses the technical challenges, clinical implications, and future directions for integrating these innovations into routine practice. Advances in portal pressure measurement hold significant promise for enhancing decision-making and outcomes in liver transplantation.
Response rates, survival status and adverse events of placebo in randomized control trials for hepatocellular carcinoma: A meta-analysis.
Chen WY, Chen Q, Wang CC … +6 more , Zhang CY, Chen SK, Meng ZQ, Han P, Dong S, Chen QW
World J Hepatol · 2025 Aug · PMID 40901596 · Full text
BACKGROUND: In randomized controlled trials (RCTs), the placebo arm has often been ignored as the attention tends to be focused on the treatment arm. We undertook a meta-analysis based on the data from the placebo arm in...
BACKGROUND: In randomized controlled trials (RCTs), the placebo arm has often been ignored as the attention tends to be focused on the treatment arm. We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carcinoma (HCC), the response rates and survival status, and adverse events (AEs) were summarized and evaluated. AIM: To systematically evaluate the response rates, survival status and AEs in the placebo arms of RCTs for HCC. METHODS: A systematic search was performed on PubMed, Ovid MEDLINE, Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC, published until December 31, 2023. Statistical analysis was performed using R statistical software (version 4.3.2). RESULTS: A total of 18 RCTs, involving 2390 patients, met the criteria for inclusion in the meta-analysis. The pooled overall disease control rate and objective response rate in the placebo group were 38% [95% confidence interval (CI): 33%-42%] and 1% (95%CI: 1%-2%), respectively. Overall survival and progression-free survival in the placebo group were 7.9 months (95%CI: 7.6-8.31 months) and 1.9 months (95%CI: 1.6-2.1 months), respectively. The incidence of grade 3 or 4 AEs was 37% (95%CI: 30%-43%). Additionally, the incidence of interruptions or dose reductions due to AEs was 20% (95%CI: 13%-27%), while the incidence of treatment discontinuation due to AEs was 9% (95%CI: 6%-12%). CONCLUSION: Over one-third of advanced HCC patients exhibit therapy-free disease control, with placebo-arm AEs observed. These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.
Hepatitis B virus rtCYE/rtCYEI mutations may contribute limited tenofovir resistance: Analysis of a large sample of Chinese patients.
Si LL, Fan ZP, Liu WH … +10 more , Chen RJ, Chen XY, Ji D, Li L, Chen C, Liao H, Wang J, Xu DP, Zhao J, Liu Y
World J Hepatol · 2025 Aug · PMID 40901595 · Full text
BACKGROUND: Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I (rtCYE/rtCYEI) mutations in the hepatitis B virus (HBV) reverse-transcriptase (RT) region are associated with tenofovir disoproxil fumarate (TDF) resistan...
BACKGROUND: Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I (rtCYE/rtCYEI) mutations in the hepatitis B virus (HBV) reverse-transcriptase (RT) region are associated with tenofovir disoproxil fumarate (TDF) resistance is controversial. AIM: To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection. METHODS: A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled. All patients received nucleoside/nucleotide analogues (NAs) therapy, and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis. RESULTS: The detection rates of a single mutation of rtS106C, rtH126Y, rtD134E, and rtL269I were 8.21%, 3.20%, 2.55% and 61.49% in 23718 genotype C patients, and 1.31%, 1.76%, 0.21%, and 92.33% in 4266 genotype B patients, respectively. The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients, accounting for 0.042% of all patients. These 12 patients had received NA treatments except TDF before testing. Among them, 6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations, and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations. Compared with the wild-type (WT) strain, the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%, and TDF susceptibility reduced by less than 2-fold, but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility. Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain. In the clinic, emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment. CONCLUSION: HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.
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