World J Hepatol [JOURNAL]
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200 papers
Histone lactylation: A key epigenetic modulator in the pathogenesis of metabolic dysfunction-associated steatohepatitis and alcoholic steatohepatitis.
Singh MM, Shah A, Rajak S … +2 more , Chaturvedi CP, Sinha RA
World J Hepatol · 2025 Dec · PMID 41479511 · Full text
Metabolic dysfunction-associated steatohepatitis (MASH) and alcoholic steatohepatitis (ASH) are severe forms of chronic liver disease, characterized by inflammation, oxidative stress, lipid dysregulation, and fibrosis. E...
Metabolic dysfunction-associated steatohepatitis (MASH) and alcoholic steatohepatitis (ASH) are severe forms of chronic liver disease, characterized by inflammation, oxidative stress, lipid dysregulation, and fibrosis. Epigenetic changes, including acetylation, methylation, phosphorylation, ubiquitination, sumoylation, and lactylation of histones, dynamically regulate gene expression by altering the chromatin structure. Emerging evidence highlights histone modifications as chief contributors to the pathogenesis of chronic liver diseases. Lactylation which is a novel post-translational modification (PTM) of histone, has been observed as a crucial contributor to liver physiology as well as pathobiology. This modification, characterized by the addition of lactate to lysine residues on histones, influences gene expression and cellular metabolism in the liver. Intriguingly, elevated lactate levels in the liver, resulting from either chronic alcohol consumption or a high-fat/fructose-rich diet, may promote histone lactylation, particularly at histone 3 at lysine 18 (H3K18), which facilitates the transcription of pro-inflammatory and fibrogenic genes. This process not only intensifies hepatic inflammation and fibrosis but also disrupts normal metabolic pathways, resulting in further liver damage. This review aims to elucidate the role of histone lactylation in MASH. Although a direct demonstration of histone lactylation in ASH has not yet been reported, the altered lactate metabolism in ASH suggests that histone lactylation may significantly contribute to its pathogenesis. Finally, we explore novel strategies targeting histone lactylation to mitigate liver injury and improve disease management in MASH and ASH.
Clinical study on the efficacy of laparoscopic hepatectomy the retroperitoneal approach for treating liver tumors.
Fei ZH, Duan XF, Feng LH … +3 more , Wang ZN, Chen YS, Sun ZW
World J Hepatol · 2025 Dec · PMID 41479510 · Full text
BACKGROUND: Laparoscopic hepatectomy has been widely accepted for the treatment of liver tumors. Compared with open surgery, it provides a reduced hospital stay, less intraoperative blood loss, less trauma, and fewer inc...
BACKGROUND: Laparoscopic hepatectomy has been widely accepted for the treatment of liver tumors. Compared with open surgery, it provides a reduced hospital stay, less intraoperative blood loss, less trauma, and fewer incisional infections, without affecting tumor outcomes. However, lesions in the right lobe of the liver are deep and obstructed by the ribs, making exposure difficult and increasing the degree of surgical difficulty; thus, liver tumors in the deep right lobe pose technical challenges in standard laparoscopic surgery. AIM: To investigate the safety and efficacy of laparoscopic retroperitoneal partial hepatectomy for liver tumors. METHODS: The clinical data of 72 patients who underwent laparoscopic retroperitoneal partial hepatectomy for liver tumors between January 2018 and December 2024 at the First People's Hospital of Yunnan Province were analyzed. Of the 72 patients included, 34 were male and 38 were female, with ages ranging from 34 years to 72 years (median age, 45 years). The tumors were all located in the right lobe of the liver, with 30 cases in segment S6, 27 cases in segment S7, and 15 cases in segment S8; the mean tumor diameter was 7.5 ± 3.4 cm. The postoperative tumor indices, liver function, and postoperative complications were analyzed to evaluate the clinical efficacy of laparoscopic partial hepatectomy the retroperitoneal approach. RESULTS: The surgeries were successfully completed in all patients, and conversion to open surgery was required in 10 patients. The mean operative time, blood loss, drain retention time, and length of postoperative hospital stay were 140 ± 30 minutes, 150 ± 46 mL, 3.8 ± 1.2 days, and 8.3 ± 5.3 days, respectively. Liver function tests returned to normal in all patients within two weeks of surgery. Fifteen patients developed atelectasis and pleural effusion and were managed with incision and drainage and antibiotics. Two patients developed uncomplicated minimal ascites, and the remaining patients had no perioperative complications, such as abdominal hemorrhage, infection, liver failure, bile leakage, and other adverse events. All patients were successfully treated. CONCLUSION: Laparoscopic retroperitoneal partial hepatectomy is a safe and effective approach for right hepatic space-occupying lesions, particularly in segments S6, S7, and S8, with fewer postoperative complications, less trauma, and faster recovery times. This procedure provides a new surgical access for resection of deep tumors in the right lobe of the liver and has clear clinical implications.
Performance of artificial intelligence in predicting hepatocellular carcinoma recurrence after thermal ablation: A systematic review.
Posa A, Lippi M, Barbieri P … +2 more , Andreani EV, Iezzi R
World J Hepatol · 2025 Dec · PMID 41479509 · Full text
BACKGROUND: Recurrence prediction of hepatocellular carcinoma (HCC) after thermal ablation represents a challenge that can impact patients' quality of life. Artificial intelligence (AI)-based radiomics models applied to...
BACKGROUND: Recurrence prediction of hepatocellular carcinoma (HCC) after thermal ablation represents a challenge that can impact patients' quality of life. Artificial intelligence (AI)-based radiomics models applied to various imaging modalities can improve recurrence prediction, therefore guiding therapeutic decisions. AIM: To evaluate the effectiveness of AI-driven predictive models in predicting HCC recurrence. METHODS: A systematic literature search in PubMed and Scopus was performed, and a total of ten studies were included in this systematic review. All studies included response prediction evaluation with AI models for patients who underwent thermal ablation for HCC. Deep learning and machine learning algorithms were utilized to evaluate the predictive performance and accuracy through metrics such as the area under the curve and concordance index. RESULTS: The developed models demonstrated high accuracy in predicting local progression and recurrence, allowing a solid risk stratification. In particular, the integration of imaging data and clinical-laboratory variables optimized treatment selection, highlighting the superior ability of imaging models to predict therapeutic outcomes compared to clinical parameters alone. Furthermore, radiomic analysis of follow-up imaging enabled highly accurate detection of ablation site recurrence. CONCLUSION: AI-driven predictive models based on multimodal radiomic analyses integrated with clinical data represent promising tools for predicting tumor recurrence after thermal ablation in HCC patients.
Refractory autoimmune hepatitis in children: Considerations for assessment and management.
Valamparampil J, Brown RM, McKiernan P
World J Hepatol · 2025 Dec · PMID 41479508 · Full text
Refractory autoimmune hepatitis (AIH) is defined as intolerance of or unresponsiveness to standard immunosuppression and occurs in 10%-20% of children with AIH. Lack of response or slower than expected response to induct...
Refractory autoimmune hepatitis (AIH) is defined as intolerance of or unresponsiveness to standard immunosuppression and occurs in 10%-20% of children with AIH. Lack of response or slower than expected response to induction of remission with steroids, despite good compliance, might be the first clue to refractory AIH. Refractoriness to treatment is associated with an 11.7 times higher risk for liver transplantation or death due to liver disease. The first and foremost consideration for the management is to assess compliance with treatment. It is then important to re-evaluate the diagnosis, assess alternative aetiologies which can mimic the clinical, serological, and histological features of AIH, and address the presence of extra-hepatic co-morbidities. It is important to consider the specific clinical situations, previous therapy, and prior adverse effects before deciding on the most appropriate treatment regimen in refractory AIH. Consideration also should be given to compliance with previous therapy, need for drug level monitoring, growth potential, available formulations, route of administration of medication, and children's and families' preferences before deciding on the therapy. Treatment should be decided and monitored only in specialized hepatology centers.
Hepatic enhancement and signal intensity analysis on magnetic resonance imaging as prognostic biomarkers in advanced chronic liver disease.
Stanciu BI, Iojiban M, Morariu-Barb A … +4 more , Caraiani C, Procopet B, Stefanescu H, Lupsor-Platon M
World J Hepatol · 2025 Dec · PMID 41479507 · Full text
BACKGROUND: Advanced chronic liver disease is a progressive condition associated with high morbidity and mortality, leading to complications such as decompensation and hepatocellular carcinoma. Although prognostic scores...
BACKGROUND: Advanced chronic liver disease is a progressive condition associated with high morbidity and mortality, leading to complications such as decompensation and hepatocellular carcinoma. Although prognostic scores such as the Child-Pugh score (which combines clinical assessment and laboratory parameters) and laboratory-based models, including Model for End-Stage Liver Disease (MELD) 3.0, albumin-bilirubin (ALBI) grade, and fibrosis-4 (FIB-4), are often used, their accuracy is limited by subjective assessments and variability in laboratory results. The Functional Liver Imaging Score (FLIS), a semi-quantitative magnetic resonance imaging (MRI) measure of liver function, may also be influenced by observer variability. This emphasizes the need for objective, reproducible tools to improve risk stratification and support treatment decision-making. AIM: To evaluate the prognostic value of hepatic enhancement (HE) and signal intensity measured by gadoxetate disodium-enhanced MRI. METHODS: In this retrospective cohort study, 100 patients with advanced chronic liver disease underwent gadoxetate-enhanced MRI. HE and signal intensity were measured quantitatively in liver segments III, VI, VIII, and the caudate lobe, and global values were calculated by averaging segmental measurements. Correlations were assessed with FLIS, Child-Pugh, MELD 3.0, ALBI, FIB-4, liver stiffness (FibroScan), and hepatic venous pressure gradient. Cox regression and receiver operating characteristic analysis were used to evaluate associations with hepatic decompensation, mortality, and hepatocellular carcinoma (HCC) occurrence during follow-up. RESULTS: Global HE showed a significant correlation with FLIS ( = 0.797), Child-Pugh ( = -0.589), MELD 3.0 ( = -0.658), ALBI ( = -0.599), FIB-4 ( = -0.308), liver stiffness ( = -0.470), and hepatic venous pressure gradient ( = -0.340). Lower HE was significantly associated with a higher risk of decompensation and mortality in univariate Cox regression. After adjustment for MELD 3.0, etiology, and prior HCC, segment VI HE remained independently predictive of mortality. At 12 months, HE improved risk stratification for mortality and reduced unnecessary interventions by 11 per 100 patients at a 10% threshold in the decision curve analysis. HE had an area under the receiver operating characteristic curve of 0.74 for predicting decompensation and 0.74 for predicting mortality. HE was higher in patients who developed or experienced recurrence of HCC during follow-up, but this was not statistically significant ( = 0.1). CONCLUSION: Lower HE in segment VI improved prognostic classification of high-risk patients. These patients align with Baveno VII criteria for intensified management, supporting the potential role of HE in risk-adapted surveillance.
arthropathy following glucocorticoid treatment for severe alcohol-associated hepatitis: Five case reports.
Herms Q, Torres S, Kamath PS … +2 more , Gratacós-Ginès J, Pose E
World J Hepatol · 2025 Dec · PMID 41479506 · Full text
BACKGROUND: Glucocorticoids (GC) are the cornerstone in the treatment of severe alcohol-associated hepatitis (SAH) but may be associated with adverse events. CASE SUMMARY: We report a prospective series of patients with...
BACKGROUND: Glucocorticoids (GC) are the cornerstone in the treatment of severe alcohol-associated hepatitis (SAH) but may be associated with adverse events. CASE SUMMARY: We report a prospective series of patients with SAH who were treated with GC and developed arthropathy within 2 weeks of GC cessation. Five patients were included in this series, three of whom were women. All patients underwent ultrasound evaluation and were referred to the Rheumatology Clinics. Final diagnoses were: Arthralgia associated with GC cessation ( = 3), polymyalgia rheumatica ( = 1) and psoriatic arthritis ( = 1). Joint soreness was the main symptom, whereas arthritis occurred rarely. Patients with arthralgia associated with GC cessation required longer regimes of GC and tapering strategies but remained free of symptoms and specific treatment in the long term. CONCLUSION: arthropathy may occur following GC for SAH. Close monitoring and tapering regimes are advised.
He-He-Shu-Yang formula alleviates liver fibrosis by inhibiting hepatic stellate cell activation and .
Zeng FL, Shi MJ, Mo YS … +3 more , Xiao HM, Xie YB, Chi XL
World J Hepatol · 2025 Dec · PMID 41479505 · Full text
BACKGROUND: Inhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer. However, modern medicine currently lacks direct anti-fibrotic drugs. He-He-S...
BACKGROUND: Inhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer. However, modern medicine currently lacks direct anti-fibrotic drugs. He-He-Shu-Yang formula (HHSY) is a renowned Chinese medicine for the treatment of liver fibrosis. However, its mechanism of action has not been fully unraveled. AIM: To explore the efficacy and mechanism of action of HHSY through and experiments. METHODS: A liver fibrosis rat model (carbon tetrachloride-induced) was treated with low- or high-dose HHSY (10.42 g/kg or 20.84 g/kg) or with colchicine (1 mg/kg) for 9 weeks. , LX-2 human hepatic stellate cells (HSCs) were activated using transforming growth factor-β1 and subsequently treated with HHSY-containing serum or a nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) inhibitor. Through high-performance liquid chromatography, histopathology (hematoxylin and eosin, Masson), immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction analyses, we demonstrated that HHSY inhibited HSC activation and suppressed the NOX4/reactive oxygen species (ROS)/nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) pathway. RESULTS: , HHSY improved liver function and alleviated liver pathology, including reducing inflammatory cell infiltration, and liver fibrosis in carbon tetrachloride rats. with more significant effects at higher doses. Immunohistochemistry revealed that HHSY could decrease alpha-smooth muscle actin, NOX4, and NLRP3 expression, as well as serum ROS levels (O and HO, < 0.05). Western blot analysis confirmed HHSY also reduced NLRP3 protein levels ( < 0.05). , HHSY at 1.25% or 2.5% reduced the levels of mRNA, NOX4 protein and mRNA, ROS production, and and mRNA in activated LX-2 cells ( < 0.05). CONCLUSION: HHSY effectively treats liver fibrosis, likely by inhibiting HSC activation through the NOX4/ROS/NLRP3 pathway. This underscores HHSY's clinical relevance as a potential therapeutic option for liver fibrosis.
Impact of age on autoimmune hepatitis: A comparative study of patients diagnosed before and after sixty.
Delgado J, Fuentes M, Simian D … +2 more , Poniachik J, Urzúa Á
World J Hepatol · 2025 Dec · PMID 41479504 · Full text
BACKGROUND: Autoimmune hepatitis (AIH) is characterized by inflammation, hepatocyte necrosis, autoantibodies, and elevated serum globulin levels. It can present at any age, with peaks reported at 30 years and after 60 ye...
BACKGROUND: Autoimmune hepatitis (AIH) is characterized by inflammation, hepatocyte necrosis, autoantibodies, and elevated serum globulin levels. It can present at any age, with peaks reported at 30 years and after 60 years. No national studies have evaluated the impact of age at diagnosis on AIH presentation and outcomes. AIM: To compare the presentation and progression of AIH in patients diagnosed before and after the age of 60 years. METHODS: This cross-sectional analytical study included biopsy-confirmed AIH patients with at least one year of follow-up at Hospital Clínico Universidad de Chile, Santiago, Chile. Demographic, clinical, laboratory, and treatment response variables were analyzed. Group comparisons (diagnosis before or after 60 years) were performed using the test for qualitative variables and the Mann-Whitney test for quantitative variables (significance < 0.05). RESULTS: Ninety-seven AIH patients were included; 85% were female, with a median age of 53 years (range 18-83 years). Forty-one percent were diagnosed after the age of 60. Younger patients exhibited more jaundice at diagnosis (75% 44%, = 0.02) and higher aminotransferases levels (median alanine aminotransferase 998 IU/mL 334 IU/mL, = 0.0002). In contrast, at diagnosis, ascites was more prevalent in patients over 60 (13% 2%, = 0.028), and advanced fibrosis (F3-F4) was more frequent in this group (68% 41%, = 0.020). Biochemical response at six months was similar between groups, despite lower corticosteroid doses being administered to patients over 60 years. CONCLUSION: AIH in patients over 60 presented with less jaundice, lower aminotransferases levels, greater fibrosis, and more ascites. Biochemical response was similar independently of age and despite lower prednisone doses administered in patients over 60 years.
Generic brand forms of direct acting antivirals for hepatitis C virus treatment in Egyptian children.
Mogahed E, Ghita H, Enayet A … +2 more , Yasin N, El-Karaksy H
World J Hepatol · 2025 Dec · PMID 41479503 · Full text
BACKGROUND: Direct acting antivirals have revolutionized hepatitis C virus (HCV) treatment. However, the high price of the brand forms is a barrier for their use in resource limited countries as Egypt. AIM: To assess the...
BACKGROUND: Direct acting antivirals have revolutionized hepatitis C virus (HCV) treatment. However, the high price of the brand forms is a barrier for their use in resource limited countries as Egypt. AIM: To assess the safety and efficacy of the generic sofosbuvir (SOF)/ledipasvir (LED) in Egyptian HCV-infected children and to compare the results with the brand form. METHODS: This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing > 35 kg. Collected data included: Age, sex, risk factors of HCV acquisition, comorbidities, liver functions, HCV viral load, degree of hepatic fibrosis, sustained virologic response (SVR) and frequency of treatment adverse effects. Patients who received the generic form of SOF/LED (Ledisbuvir) were compared to patients who received the brand form (Harvoni) regarding SVR and frequency of adverse events. RESULTS: The study included 43 patients who received Ledisbuvir and 73 who received Harvoni. All patients achieved SVR. Treatment side effects were mild, transient and comparable in both groups. CONCLUSION: The use of generic SOF/LED in HCV infected children is safe and effective. It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.
Stereotactic body radiation therapy in patients with unresectable hepatocellular carcinoma and portal vein tumor thrombosis.
Khosla D, Gade VKV, Kapoor R … +10 more , Singh G, Singh R, Taneja S, Premkumar M, Kalra N, De A, Bhujade H, Verma N, Duseja A, Gupta R
World J Hepatol · 2025 Dec · PMID 41479502 · Full text
BACKGROUND: About 35%-50% of patients with hepatocellular cancer (HCC) present with portal venous tumor thrombosis (PVTT). Stereotactic body radiation therapy (SBRT) offers a promising approach for locoregional treatment...
BACKGROUND: About 35%-50% of patients with hepatocellular cancer (HCC) present with portal venous tumor thrombosis (PVTT). Stereotactic body radiation therapy (SBRT) offers a promising approach for locoregional treatment in patients with HCC with PVTT. This study aimed to report the clinical characteristics and early outcomes of patients with unresectable HCC and PVTT treated with SBRT. AIM: To report the clinical characteristics and early outcomes of patients with unresectable HCC and PVTT treated with SBRT. METHODS: This retrospective, single-institution study included adult HCC patients with PVTT treated between March 2020 and December 2023. Eligibility criteria included Child-Pugh A-B liver function, serum bilirubin < 3 mg/dL, Eastern Co-operative Oncology Group performance status 0-2, a normal liver volume > 700 cc, and a tumor-lumen distance > 5 mm. SBRT dose and fractionation were determined based on tumor volume and organ-at-risk constraints. Baseline clinical and dosimetric parameters were recorded. Survival analysis was performed using Kaplan-Meier curves, response was assessed at 3 months post-SBRT using the Revised Response Evaluation Criteria in Solid Tumors 1.1 criteria, and toxicity was graded per Common Terminology Criteria for Adverse Events 4.0. RESULTS: Thirty patients (median age: 65 years, 90% male) were included. Sixteen (53.3%) were Child-Pugh A, and fourteen (46.6%) were Child-Pugh B. Sixty percent had VP4 disease. SBRT doses ranged from 30-50 Gy in 5-6 fractions. The median tumor diameter was 6.1 cm, and the median follow-up was 15 months. The overall response rate was 83.3%, with a median overall survival of 13 months and progression-free survival of 10.2 months. No grade 4 toxicities were observed. CONCLUSION: SBRT has the potential to be an effective modality for locoregional control in patients with unresectable HCC with PVTT.
Pre-transplant downstaging strategies for hepatocellular carcinoma with portal vein tumor thrombus: Current therapies and future challenges.
Li ZY, Xie C, Cai HQ
World J Hepatol · 2025 Nov · PMID 41376836 · Full text
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with approximately 35%-50% of patients presenting concurrent portal vein tumor thrombus (PVTT). Untreated HCC patien...
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with approximately 35%-50% of patients presenting concurrent portal vein tumor thrombus (PVTT). Untreated HCC patients with PVTT have a median survival of only 2.5-4 months, posing significant challenges to liver transplantation outcomes. Downstaging therapies play a pivotal role in improving transplant eligibility rates and optimizing post-transplant outcomes. This systematic review summarizes current downstaging therapies, including transarterial chemoembolization, transarterial radioembolization, proton beam therapy, intraportal radiofrequency ablation, and other novel systemic modalities. In-depth analysis of their clinical applications, efficacy, and safety profiles were performed. Furthermore, the review critically evaluates future challenges, including optimized downstaging criteria, personalized and precision medicine approaches, and novel biomaterials for localized therapy for downstaged HCC patients. This review provides comprehensive theoretical and practical insights into pre-transplant downstaging for HCC with PVTT, while highlighting critical avenues for future research and clinical decision-making.
Intra-rater reliability of the 6-min walk test in people with liver cirrhosis.
Corrêa FCCR, Nader ISTP, Riolino MRS … +1 more , Silva E
World J Hepatol · 2025 Nov · PMID 41368123 · Full text
BACKGROUND: Liver cirrhosis often leads to significant impairments in functional capacity, which are associated with disease severity and prognosis. Simple, reliable, and low-cost tests are essential to monitor these pat...
BACKGROUND: Liver cirrhosis often leads to significant impairments in functional capacity, which are associated with disease severity and prognosis. Simple, reliable, and low-cost tests are essential to monitor these patients in clinical practice. The 6-min walk test (6MWT) is widely used in other chronic conditions, but its measurement properties in cirrhosis remain underexplored. AIM: To assess the reliability of the 6MWT in patients with liver cirrhosis (LC). METHODS: This cross-sectional study was conducted at a teaching hospital in Juiz de Fora-Minas Gerais. Patients diagnosed with LC at any stage of the disease and under clinical follow-up were included. Patients with grade 2 or higher encephalopathy, respiratory, and/or musculoskeletal diseases or who did not understand the test were excluded. Initially, anamnesis and anthropometric evaluation were performed, followed by the 6MWT. After 24 h the test was repeated. Descriptive statistics were used to present the data. Continuous variables were tested for normality using the Shapiro-Wilk test. The reliability of the 6MWT was tested through Bland-Altman analysis, typical error of measurement, and intraclass correlation coefficient (ICC) as well as a one-sample -test. A paired Student's -test was used to check for differences between means, and Pearson's correlation coefficient was used to verify the relationship between the two moments [first 6MWT (6MWT-1) and second 6MWT (6MWT-2)]. RESULTS: The mean difference between 6MWT-2 and 6MWT-1 was -18.9 m; the lower limit of the Bland-Altman agreement was -83.5 m, and the upper limit was 45.7 m. One participant was excluded from further analyses for being outside these limits. The typical error of measurement was 18.9 m. The ICC showed excellent reliability between the two tests (ICC = 0.97, 95% confidence internal: 0.90-0.99, < 0.001). The Student's one-sample -value was -2.35 ( = 0.03). The paired -value was 2.35 ( = 0.03). Pearson's correlation coefficient between the 6MWT-1 and 6MWT-2 was = 0.98 ( = 0.0001). CONCLUSION: The 6MWT is a test with excellent reliability. It is safe, easy to administer, inexpensive, and can be introduced into routine practice without loss of diagnostic precision in estimating the functional capacity of patients with LC.
Cytokeratin 18 fragment is associated with steatosis-associated fibrosis estimator score and lipid in patients with steatotic liver disease.
Ichikawa T, Miuma S, Yamashima M … +10 more , Yamamichi S, Koike M, Nakano Y, Yajima H, Miyazaki O, Ikeda T, Okamura T, Komatsu N, Yoshino M, Miyaaki H
World J Hepatol · 2025 Nov · PMID 41368122 · Full text
BACKGROUND: Serum cytokeratin 18 fragment (CK18F) has been developed as a new non-invasive test (NIT) for risk assessment of steatotic liver disease (SLD); however, there are few reports on its relationship with existing...
BACKGROUND: Serum cytokeratin 18 fragment (CK18F) has been developed as a new non-invasive test (NIT) for risk assessment of steatotic liver disease (SLD); however, there are few reports on its relationship with existing NITs and association with cardiometabolic risk factors (CMRFs). AIM: To clarify the relationship among CK18F, NITs, and CMRF. METHODS: We included 125 patients who were assessed for SLD and had CK18F measured in cross-sectional study. The fibrosis-4 index (FIB-4), steatosis-associated fibrosis estimator (SAFE) score, liver stiffness (LS), controlled attenuation parameter, and FibroScan-aspartate aminotransferase (FAST) score were compared with CK18F as existing NITs. RESULTS: CK18F was associated with aspartate aminotransferase, alanine aminotransferase, and triglyceride (TG). FAST and SAFE score were associated with high CK18F (> 260 U/L), but not FIB-4 or LS. The cut-off values for TG and high-density lipoprotein (HDL) cholesterol used to determine high CK18F using receiver operating characteristics analysis were 126 mg/dL and 56 mg/dL respectively. High TG (> 126 mg/dL) and low HDL (< 56 mg/dL) were associated with high CK18F. The risk of high CK18F was higher when high TG and low HDL were combined than when each was present alone. CMRF was higher in the high CK18F group, but was not associated with CK18F levels. However, when the TG and HDL criteria for CMRF were replaced by TG > 126 mg/mL and HDL < 56 mg/dL, modified CMRF (mCMRF) was associated with CK18F levels, with a higher risk of high CK18F than CMRF. CONCLUSION: CK18F is a new NIT associated with SAFE score and FAST. High TG, low HDL, and mCMRF are associated with high CK18F.
Artificial intelligence in metabolic dysfunction-associated steatotic liver disease: Machine learning for non-invasive diagnosis and risk stratification.
Hegazy MA
World J Hepatol · 2025 Nov · PMID 41368121 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, represents a growing global health burden, contributing significantly to liver-related morbidity and...
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, represents a growing global health burden, contributing significantly to liver-related morbidity and mortality. Early detection and timely intervention are essential to prevent disease progression. Conventional diagnostic methods, which rely on specialized imaging and invasive liver biopsies, underscore the need for non-invasive, cost-effective alternatives. Artificial intelligence-particularly machine learning and deep learning-has emerged as a transformative tool in MASLD diagnostics, offering improved accuracy in risk prediction, imaging interpretation, and disease stratification. This review synthesizes recent advancements in AI-based MASLD diagnostics, highlighting key models, performance metrics, and clinical applications, while addressing ongoing challenges such as data standardization, interpretability, and clinical validation.
PANoptosis in hepatocellular carcinoma: Underlying mechanisms.
Li MJ, Wen CL, Cheng HT … +2 more , Lyu HN, Han YY
World J Hepatol · 2025 Nov · PMID 41368120 · Full text
PANoptosis is an inflammatory programmed cell death pathway possessing critical characteristics of apoptosis, pyroptosis, and necroptosis. It is regulated by PANoptosome complexes, involves interaction between these thre...
PANoptosis is an inflammatory programmed cell death pathway possessing critical characteristics of apoptosis, pyroptosis, and necroptosis. It is regulated by PANoptosome complexes, involves interaction between these three key programmed cell death pathways, yet is distinct from any alone. PANoptosis holds vital significance in liver-related diseases, particularly hepatocellular carcinoma (HCC). This article summarizes research on the mechanism and treatments of PANoptosis in HCC. Current research has partially elucidated PANoptosis-related mechanisms in HCC and identified several molecules modulating it. Therapeutic strategies targeting PANoptosis hold significant promise. Investigations into these critical molecules have led to the development of traditional targeted drug therapies and emerging strategies like nanotechnology-based immunocombination therapies. However, there are still challenges in the mechanistic and pharmacological studies of PANoptosis in HCC, including the bidirectional regulation of key apoptotic factors, specific molecular mechanisms, and preclinical models. This article offers a new orientation for studying the pathogenesis and potential therapeutic strategies for HCC.
Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis.
Zhang CY, Liu S, Sui YX … +1 more , Yang M
World J Hepatol · 2025 Nov · PMID 41368119 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, affecting more than 30% of adults and 7%-14% of youths globally. MASLD and its advanced form of metabolic dysfunc...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, affecting more than 30% of adults and 7%-14% of youths globally. MASLD and its advanced form of metabolic dysfunction-associated steatohepatitis (MASH) can progress to liver cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective therapies for MASLD and MASH remain limited. Accumulating evidence indicates that short-chain fatty acids (SCFAs) modulate the activation of hepatic innate and adaptive immune cells, influencing liver inflammation and fibrosis. Moreover, SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity, affecting MASLD progression. This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation, fibrosis, and energy metabolism. Several key molecular signaling pathways are discussed. Clinical trials aiming to modulate SCFA production through different treatments are reviewed. Collectively, emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.
Redefining fatty liver as metabolic dysfunction-associated steatotic liver disease: Implications of nomenclature changes for patients with diabetes.
Correa TL, Duong N
World J Hepatol · 2025 Nov · PMID 41368118 · Full text
The evolving nomenclature from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) aims to better encompass the metabolic context of the disease. This change has...
The evolving nomenclature from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) aims to better encompass the metabolic context of the disease. This change has significant implications for patients with type 2 diabetes mellitus (T2DM), given the frequent overlap between these conditions. This minireview explores the rationale behind the change, compares diagnostic criteria, and evaluates the impact of the MASLD framework on disease prevalence, characterization, and outcomes in T2DM patients. The updated MASLD criteria include all individuals with T2DM and hepatic steatosis, emphasizing metabolic dysfunction as the primary driver. In contrast, the NAFLD definition necessitates excluding other chronic liver diseases and verifying the absence of significant alcohol consumption, leading to a narrower diagnostic framework. Both metabolic dysfunction-associated fatty liver disease and MASLD identify a higher prevalence of steatotic liver disease, particularly among T2DM patients, compared to NAFLD. Notably, the MASLD framework introduces metabolic and alcohol-associated liver disease to account for dual etiologies involving alcohol use, which is common in T2DM populations but previously excluded under NAFLD criteria. While the new definitions enhance clinical relevance and inclusivity, they also highlight challenges such as unrecognized medication-induced steatosis and the need for reclassification in ongoing T2DM clinical trials. Emerging evidence supports enhanced screening strategies (, fibrosis-4) and metabolic-targeted treatments for MASLD in T2DM patients. The successful integration of MASLD into clinical practice will require system-wide reeducation, standardization, and multidisciplinary collaboration to improve outcomes for T2DM patients.
Hypertransaminasemia in non-cirrhotic critically-ill patients.
Fiore M, Cosenza G, Coppolino F … +4 more , Pota V, Sansone P, Petrou S, Pace MC
World J Hepatol · 2025 Nov · PMID 41368117 · Full text
Hypertransaminasemia - acute elevation of alanine aminotransferase and aspartate aminotransferase - is prevalent in non-cirrhotic adults admitted to the intensive care unit (ICU) and often signals extra-hepatic pathophys...
Hypertransaminasemia - acute elevation of alanine aminotransferase and aspartate aminotransferase - is prevalent in non-cirrhotic adults admitted to the intensive care unit (ICU) and often signals extra-hepatic pathophysiology rather than intrinsic liver disease. To synthesise contemporary evidence on aetiology-driven diagnosis, management and emerging biomarkers of hypertransaminasemia in critically ill patients. We performed a structured search of PubMed, EMBASE and CENTRAL (January 2010-June 2025). The search was restricted to full-text articles that were published in English in peer-reviewed journals. Hypoxic liver injury is the leading cause of hypertransaminasemia in non-cirrhotic ICU patients and is characterized by a ≥ 50% alanine aminotransferase/aspartate aminotransferase fall within 72 hours after haemodynamic stabilisation. Idiosyncratic drug-induced liver injury remains uncommon yet explains about 13% of acute liver-failure cases in Western registries. Sepsis-associated liver injury presents mainly as conjugated hyperbilirubinaemia with modest transaminase rise, whereas parenteral-nutrition-associated liver disease is dominated by cholestasis after > 2 weeks of parenteral feeding. Early optimisation of macro-/micro-circulation, rational deprescribing of hepatotoxins, rapid source control of infection and prompt transition to enteral nutrition are outcome-modifying interventions across all phenotypes. In the ICU, aminotransferase elevation should be interpreted as a dynamic biomarker of systemic distress. A pattern-recognition algorithm integrating clinical context, enzyme kinetics and novel biomarkers (glutamate dehydrogenase, microRNA-122, high-mobility group box-1) can expedite aetiology-specific therapy and deserves prospective validation.
Beyond bones: Revisiting the role of vitamin D in chronic liver disease.
Guerrero-Guerrero R, Mendez-Guerrero O, Carranza-Carrasco A … +3 more , Tejeda F, Ardon-Lopez A, Navarro-Alvarez N
World J Hepatol · 2025 Nov · PMID 41368116 · Full text
Beyond its traditional role in calcium and bone metabolism, vitamin D has emerged as a critical regulator of liver health. Its active form, calcitriol [1α,25(OH)D], signals through the vitamin D receptor (VDR), which is...
Beyond its traditional role in calcium and bone metabolism, vitamin D has emerged as a critical regulator of liver health. Its active form, calcitriol [1α,25(OH)D], signals through the vitamin D receptor (VDR), which is expressed in hepatic stellate cells, Kupffer cells, and cholangiocytes. Through this pathway, vitamin D modulates fibrosis, inflammation, oxidative stress, bile acid homeostasis, and immune responses. This review explores the growing body of evidence linking vitamin D deficiency to chronic liver diseases, including autoimmune hepatitis, primary biliary cholangitis, alcoholic liver disease, viral hepatitis B and C, and metabolic-associated steatotic liver disease. Low vitamin D levels are frequently observed in these conditions and are associated with disease severity, complications (such as spontaneous bacterial peritonitis, sarcopenia, and hepatic encephalopathy), and increased mortality. Mechanistically, vitamin D-VDR signaling inhibits profibrotic TGF-β1/SMAD pathways, downregulates proinflammatory cytokines, enhances regulatory T cell differentiation, and improves insulin sensitivity. Although preclinical studies support its protective effects, clinical trials of vitamin D supplementation have produced mixed results. Overall, vitamin D appears to influence multiple pathways in liver disease pathophysiology, and correcting its deficiency may offer clinical benefits. However, its integration into clinical care will depend on identifying responsive patient subgroups and defining optimal dosing strategies to maximize therapeutic benefit.
Non-invasive blood biomarkers for assessment of liver fibrosis in metabolic dysfunction-associated steatotic liver disease.
Zhao YH, Leng SS, Wang Y … +2 more , Kui FZ, Gan W
World J Hepatol · 2025 Nov · PMID 41368115 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) requires accurate liver fibrosis assessment for management. While liver biopsy remains the gold standard, its invasiveness drives demand for non-invasive b...
Metabolic dysfunction-associated steatotic liver disease (MASLD) requires accurate liver fibrosis assessment for management. While liver biopsy remains the gold standard, its invasiveness drives demand for non-invasive biomarkers. This review evaluates blood biomarkers for MASLD fibrosis staging. Established scores (fibrosis-4, non-alcoholic fatty liver disease fibrosis score) offer accessible screening but exhibit variable performance influenced by age, obesity, and comorbidities. Patented panels (, enhanced liver fibrosis test, FibroMeter) improve accuracy by integrating extracellular matrix or metabolic markers, though context-specific thresholds are essential. Emerging biomarkers like propeptide of type 3 collagen, Mac-2 binding protein glycosylation isomer, epigenetic markers (proliferator-activated receptor-γ methylation), and angiopoietin-like proteins a family of eight glycoproteins show promise but require large-scale validation. Genetic risk scores and multi-omics approaches face generalizability challenges. Integration strategies, such as combining serum biomarkers with liver stiffness measurement Agile scores, enhance diagnostic precision and reduce indeterminate classifications. Current tools aid risk stratification, but no single biomarker replicates biopsy-level precision. Future efforts must prioritize MASLD-specific diagnostic frameworks, standardized protocols, and multi-modal integration to enhance clinical utility and address MASLD's growing burden.
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