World J Hepatol [JOURNAL]
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200 papers
Impact of clinically significant portal hypertension on posthepatectomy liver failure: A systematic review and meta-analysis.
Ruan MH, Ye FY, Ma JN … +9 more , Qian J, Zou MH, Zhou WX, Sheng J, Guo XG, Wei D, Zhang CJ, Liu H, Liu FC
World J Hepatol · 2026 Jan · PMID 41640955 · Full text
BACKGROUND: The health challenges of partial hepatectomy in patients with clinically significant portal hypertension (CSPH) have been a subject of study for decades. No meta-analysis has systematically evaluated the rela...
BACKGROUND: The health challenges of partial hepatectomy in patients with clinically significant portal hypertension (CSPH) have been a subject of study for decades. No meta-analysis has systematically evaluated the relationship between CSPH and posthepatectomy liver failure (PHLF), despite its potential role as a critical factor in surgical decision-making. This systematic review and meta-analysis investigated the incidence of PHLF in patients with and without CSPH. AIM: To include more recent studies and focus on short-term postoperative outcomes, particularly the association between CSPH and PHLF. Additionally, stratified analyses were also performed according to CSPH and PHLF assessment methods, study design, study period, surgical technique, and underlying liver diseases. METHODS: A comprehensive literature search was conducted in EMBASE, PubMed, MEDLINE, ScienceDirect, Elsevier, and Cochrane databases using combinations of the following terms: ("portal hypertension" OR "hypertension, portal" OR "portal hypertensions") AND ("hepatectomy" OR "hepatectomies" OR "liver resection") AND ("liver failure" OR "hepatic failure" OR "liver decompensation"). Studies published from January 1996 to April 2025, 21 published studies were finally included in the systematic review and meta-analysis. The quality assessment was performed independently by using the Newcastle-Ottawa Scale. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and compared using a random-effects model. Heterogeneity was assessed with the test, and the degree of inconsistency was measured using . A value < 0.05 or > 50% indicated substantial heterogeneity. Sensitivity analysis was conducted to test the robustness of the findings and to identify potential sources of bias. RESULTS: A total of 6981 patients (1453 patients with CSPH and 5529 patients without CSPH) were finally included in this study. Compared with patients without CSPH, the incidences of PHLF increased in patients with CSPH (OR = 3.14; 95%CI: 2.45-4.02; < 0.001). Subsequent subgroup analysis suggested that the diagnostic methods for CSPH is a potential interfering factor in PHLF, the OR was maximal in hepatic venous pressure gradient measurement groups (OR = 15.61; 95%CI: 2.11-115.35; = 0.007). CONCLUSION: The presence of CSPH should be considered as a significant risk factor, it still should be taken into account seriously prior to surgery and needs strict perioperative management. Meanwhile, different methods of diagnosing CSPH could influence PHLF.
Whole-exome sequencing illuminates unexplained pediatric cholestatic liver disease.
Yodoshi T
World J Hepatol · 2026 Jan · PMID 41640954 · Full text
Unexplained liver disease in infants and children remains a significant diagnostic challenge as the spectrum of noninfectious pediatric liver disease expands. Timely, accurate etiologic assignment remains central to opti...
Unexplained liver disease in infants and children remains a significant diagnostic challenge as the spectrum of noninfectious pediatric liver disease expands. Timely, accurate etiologic assignment remains central to optimal care and resource allocation. Advances in next-generation sequencing, particularly whole-exome sequencing (WES), have transformed evaluation by enabling rapid identification of monogenic disorders that previously eluded standard algorithms. In this editorial, we synthesize recent evidence showing that comprehensive genetic testing substantially improves etiologic diagnosis in pediatric hepatology. WES markedly increases diagnostic yield in infants with cholestasis and in children with cryptogenic aminotransferase elevations, directly influencing management and outcomes. We compare yields across international reports from Asia, North America, and Europe, illustrating how WES and broad gene panels uncover heterogeneous genetic contributors to pediatric liver disease. We also address practical issues, including decreasing costs, faster turnaround times, and the importance of integrating conventional investigations with modern genomics. Finally, we emphasize that while WES is a powerful tool to "decode" unexplained disease and guide precision therapies, it must complement, not replace, careful clinical assessment and, in selected cases, liver biopsy. An integrated approach is essential for navigating heterogeneity, avoiding unnecessary procedures, and advancing personalized medicine in pediatric hepatology worldwide to improve outcomes and equity.
Clinical spectrum and genotype-phenotype correlation of mutations in children: Insights from a North Indian cohort.
Thunga C, Mitra S, Babbar A … +4 more , Lal R, Pal A, Kakkar N, Lal SB
World J Hepatol · 2026 Jan · PMID 41640953 · Full text
BACKGROUND: Progressive familial intrahepatic cholestasis type 3, caused by mutations in the gene, is a rare genetic disorder. Although severe phenotypes due to biallelic mutations are well described, emerging data seem...
BACKGROUND: Progressive familial intrahepatic cholestasis type 3, caused by mutations in the gene, is a rare genetic disorder. Although severe phenotypes due to biallelic mutations are well described, emerging data seem to suggest the clinical relevance of monoallelic variants. AIM: To describe the clinical spectrum and genotype-phenotype correlation of mutations in children in a cohort of North Indian children. METHODS: This is a retrospective analysis of a prospectively maintained database from a single tertiary care centre. Children (≤ 18 years) with mutations between January 2021 and March 2025 were analysed. The clinical presentation, laboratory investigations, genetic sequencing and outcomes were recorded. Patients were stratified into group 1 (homozygous/compound heterozygous) and group 2 (heterozygous). Variant pathogenicity was assessed using the American College of Medical Genetics guidelines and available predictive tools. RESULTS: Of the 26 patients, 16 had biallelic mutations, and 10 had monoallelic mutations. Group 1 exhibited higher rates of positive family history (75% 30%, = 0.04), ascites (43.2% 0%, = 0.02), larger varices (40% 0%, = 0.009), higher gamma glutamyl transferase levels (171 U/L 38 U/L, = 0.007), and lower platelet counts (162 × 10/L 415 × 10/L, = 0.007). Notably, two-thirds of patients in group 1 experienced disease progression, and one-third died during follow-up. Certain missense variants (, c.2860T>C) and all nonsense variants were linked to rapid deterioration. Most children in group 2 had transient cholestasis with a good outcome, but two older children succumbed. CONCLUSION: Mutations in the gene contribute significantly to pediatric chronic liver disease. Patients with severe biallelic mutations frequently experience a progressive disease course, whereas those with monoallelic mutations may progress slowly. Genetic testing for should be considered in children with cryptogenic chronic liver disease, especially those with high gamma-glutamyltransferase cholestasis and portal hypertension.
Enhanced surgical tolerance of schistosomiasis-induced fibrotic liver following treatment with plant extract.
Alghamdi TH
World J Hepatol · 2026 Jan · PMID 41640952 · Full text
BACKGROUND: leaf extract (ZSCLE) can be used to treat hepatic schistosomiasis. However, its role as an anti-inflammatory and anti-proliferative agent remains unexplored. AIM: To assess the therapeutic potential of ZSCLE...
BACKGROUND: leaf extract (ZSCLE) can be used to treat hepatic schistosomiasis. However, its role as an anti-inflammatory and anti-proliferative agent remains unexplored. AIM: To assess the therapeutic potential of ZSCLEs in hamsters infected with () undergoing 50% liver resection (LR). METHODS: Fifty hamsters were divided into five groups (10 hamsters each), with group I serving as the control; group II received ZSCLE treatment only; group III was infected with but was untreated; group IV was infected with and received ZSCLE treatment; group V was infected with and underwent ZSCLE treatment and 50% LR. Each group was analyzed using DNA flow cytometry, and oxidative stress (nitric oxide levels), inflammatory markers (tumor necrosis factor-α and interferon-γ), and liver biomarkers were assessed. Histopathological examination was conducted for all groups. RESULTS: Compared with the infected untreated group, the ZSCLE-treated group showed a significant 70.2% reduction in hepatic tissue egg load (3459.5 ± 191.3 1032 ± 25.1, < 0.001), and the ZSCLE-treated group that underwent surgical resection showed a 71.8% decrease (2021.7 ± 190.2 7193.3 ± 103.4, < 0.001). Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin levels were higher in group III than in group I, group IV, and group V ( < 0.0001). The liver regeneration rate (%) was significantly higher in group IV and group V than in group III (median values: 45.18%, 47.93% 28.31%). Pathological examination revealed fewer granulomas in group V. CONCLUSION: ZSCLE-LR is a potent agent against schistosomiasis-induced hepatic damage, exhibiting a significant role in promoting hepatic regeneration. Further molecular-level studies are warranted to investigate the phytochemical properties of ZSCLE and its potential applications in managing schistosomiasis-induced hepatic fibrosis.
Remote telerehabilitation for frailty management in liver transplant candidates: A feasible yet underutilized strategy.
Cui X, Yin BQ, Chen L
World J Hepatol · 2026 Jan · PMID 41640951 · Full text
This letter reviews Loschi 's study evaluating structured telerehabilitation for frail cirrhotic liver transplant candidates, which fills a critical pre-transplant care gap. The video-based program, using low-cost tools...
This letter reviews Loschi 's study evaluating structured telerehabilitation for frail cirrhotic liver transplant candidates, which fills a critical pre-transplant care gap. The video-based program, using low-cost tools and asynchronous sessions, improved liver frailty index reduction and function in adherent patients (29.8%) although a high attrition rate (70%) highlighted engagement challenges. Limitations include a small, non-randomized sample, mixed frailty subgroups, and unexplored long-term effects. Future directions emphasize hybrid models, patient-centered barrier analysis, and policy-driven frailty screening. This work advances digital health for cirrhosis; however, larger trials are needed to optimize outcomes.
Blood markers transient elastography for liver stiffness and steatosis in metabolic dysfunction-associated steatotic liver disease.
Joseph A, Mathew S, Nair HR
World J Hepatol · 2026 Jan · PMID 41640950 · Full text
BACKGROUND: Liver biopsy, once the gold standard for evaluating liver fibrosis and steatosis, has been largely replaced in routine clinical practice by non-invasive tools like Fibroscan, which evaluate liver stiffness me...
BACKGROUND: Liver biopsy, once the gold standard for evaluating liver fibrosis and steatosis, has been largely replaced in routine clinical practice by non-invasive tools like Fibroscan, which evaluate liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). While Fibroscan is well-validated, cost and accessibility challenges limit its use for regular follow-up, especially in primary care. AIM: To investigate the diagnostic accuracy and correlation of blood-based parameters fibrosis 4 (FIB-4) score, aspartate transaminase to platelet ratio index (APRI), neutrophil-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil percentage-to-albumin ratio (NPAR) with LSM and CAP values in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. METHODS: In a cross-sectional study of 300 MASLD patients we compared FIB-4, APRI, NLR, PLR, and NPAR with LSM and CAP values. Patients were categorized based on LSM into less fibro-progressed (F0-F2) and advanced fibro-progressed (F3-F4) groups, and by CAP into S1, S2 and S3 categories. Sensitivity, specificity, positive predictive value, and negative predictive value of the markers were analyzed, and receiver operating characteristic curves were plotted. RESULTS: FIB-4 [ = 0.537, < 0.001; area under curve (AUC) = 0.806; diagnostic accuracy = 75.63%] and APRI ( = 0.513, < 0.001; AUC = 0.772) showed strong correlations with LSM, confirming their reliability for LSM. APRI and FIB-4 are validated against fibrosis in liver biopsy, our results demonstrate comparable performance between these scores and LSM by Fibroscan. PLR exhibited high specificity (98.0%) but showed negative correlation with LSM ( = -0.317, < 0.01). For CAP, NPAR demonstrated the highest specificity (97.67%) and positive predictive value (91.31%), followed by NLR (specificity 92.77%, positive predictive value 91.58%), though AUC values were modest (0.562 and 0.540, respectively). CONCLUSION: FIB-4 and APRI which are robust non-invasive markers for fibrosis, correlates well with LSM as well. NPAR shows potential for steatosis assessment using CAP, warranting further validation. Negative correlation of PLR might suggest its role in liver stiffness evaluation. These markers both conventional and novel, can be used for repeated measurements during follow-up in primary care settings.
Transforming growth factor beta reduces proprotein convertase subtilisin/kexin type 9 in the supernatant of hepatic stellate cells.
Bundschuh J, Neumann M, Zimny S … +2 more , Spirk M, Buechler C
World J Hepatol · 2026 Jan · PMID 41640949 · Full text
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is abundantly expressed by hepatocytes and regulates the uptake of low-density lipoprotein by these parenchymal cells. Little research has been conducted...
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is abundantly expressed by hepatocytes and regulates the uptake of low-density lipoprotein by these parenchymal cells. Little research has been conducted on PCSK9 expression in non-hepatocyte liver cells. AIM: To investigate PCSK9 levels in the supernatant of different liver cells and its regulation in hepatic stellate cells (HSCs). METHODS: PCSK9 levels were measured in the cell culture medium of primary human hepatocytes, HepG2 and Huh7 cells, primary human HSCs, the HSC cell line LX-2, primary human Kupffer cells, and primary human sinusoidal endothelial cells. The effects of cytokines, adipokines, lipopolysaccharide, transforming growth factor beta (TGF-β) and ligands of nuclear receptors on PCSK9 levels in LX-2 cells during 24 hours of culture were determined using enzyme-linked immunosorbent assay. RESULTS: Primary human hepatocytes, HepG2, Huh7, HSCs, and LX-2 cells secreted significant levels of PCSK9. There were low levels of PCSK9 in the supernatant of Kupffer cells and sinusoidal endothelial cells. Interleukin-6 reduced PCSK9 in LX-2 cells to 86% of controls and lipopolysaccharide increased it by 7%, whereas tumor necrosis factor, as well as exogenous adiponectin and leptin had no effect. Chemerin-156, but not chemerin-155 or chemerin-157 isoform overexpressed in LX-2 cells, reduced PCSK9 to 84% of the controls. TGF-β reduced PCSK9 in LX-2 cell culture media to 68% of controls and lowered its cellular level. Activation of liver X receptor but not farnesoid X receptor or peroxisome proliferator-activated receptor gamma, reduced PCSK9 levels by 42% in LX-2 cell culture medium. CONCLUSION: Profibrotic TGF-β and the antifibrotic liver X receptor ligand both reduced PCSK9 in LX-2 medium, showing that PCSK9 is not a marker of HSC activation.
Phase III, multicenter, randomized, double-blind, placebo-controlled study of norursodeoxycholic acid in metabolic dysfunction-associated steatotic liver disease patients.
Panuganti VK, Alluri CV, Mohammad J … +4 more , Dundigalla MR, Madala PK, Kssvv S, Shaik A
World J Hepatol · 2025 Dec · PMID 41479524 · Full text
BACKGROUND: The norursodeoxycholic acid (norUDCA), a side chain-shortened derivative of ursodeoxycholic acid, exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated ste...
BACKGROUND: The norursodeoxycholic acid (norUDCA), a side chain-shortened derivative of ursodeoxycholic acid, exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated steatotic liver disease (MASLD). AIM: To evaluate the efficacy, safety, and tolerability of norUDCA 1500 mg compared to placebo in the patients with MASLD. METHODS: This phase III, randomized, double-blind, multi-centric, placebo-controlled trial enrolled patients with MASLD, and were randomized in 2:1 ratio to receive either norUDCA 1500 mg or placebo for 24 weeks. Efficacy and safety were rigorously evaluated through clinical, biochemical, and imaging assessments. Primary endpoints assessed alanine aminotransferase (ALT) normalization and improvement in liver stiffness (FibroScan) at week 12, while secondary endpoints included changes in nonalcoholic fatty liver disease fibrosis score, liver enzymes, lipid profile, glycosylated hemoglobin, and FibroScan-assessed liver stiffness. Safety was monitored throughout the study. RESULTS: Of 165 randomized patients, 110 received norUDCA and 55 placebos. At week 12, ALT normalization was achieved in 89% of norUDCA-treated group compared to 76% of placebo-treated group ( = 0.022); with a statistically significant adjusted mean difference ( = 0.016). Fibrosis improvement was observed in 57% of norUDCA-treated 40% in placebo-treated ( = 0.035), with highly significant adjusted mean ( = 0.002). nonalcoholic fatty liver disease fibrosis score at week 18 and 24 ( = 0.041 and = 0.032). Similarly, ALT reductions were significant at both week 18 and week 24 ( = 0.021 and = 0.035). Improvements in lipid profile trended towards norUDCA without statistical significance. Liver stiffness has improved in 90 patients in norUDCA-treated 36 patients in placebo group ( = 0.009). NorUDCA demonstrated favorable safety profile, with no serious adverse events reported, and only mild to moderate adverse events were observed. CONCLUSION: NorUDCA 1500 mg demonstrated clinically meaningful therapeutic efficacy in patients with MASLD, accompanied by consistently favorable safety profile.
Clinical and biological significance of the relationship between gut microbiota and liver disease.
Kotlyarov SN
World J Hepatol · 2025 Dec · PMID 41479523 · Full text
The gut microbiota is of growing interest to clinicians and researchers due to its elucidating extensive role in metabolic and immune mechanisms, not only in the gut but also in other organs. The liver shares a close bid...
The gut microbiota is of growing interest to clinicians and researchers due to its elucidating extensive role in metabolic and immune mechanisms, not only in the gut but also in other organs. The liver shares a close bidirectional relationship with the intestine and the gut microbiota. Disturbances in the composition of the gut microbiota can affect the immune systems of both the intestine and liver. In turn, bile composition also influences the gut microbiota. Disruption of this balance can arise from various causes and may significantly impact intestinal and liver health. Therefore, the aim of the current review is to discuss the biological relationships between the gut microbiota and liver function as well as the clinical significance of their disturbances.
Targeting sirtuin 1/nuclear factor erythroid 2-related factor 2/tumor necrosis factor-α pathway to modulate hepatic ischemia reperfusion-induced injury.
Kelleni MT, Abdelzaher WY, Adly M … +3 more , Attya ME, Fawzy MA, Ibrahim MA
World J Hepatol · 2025 Dec · PMID 41479522 · Full text
BACKGROUND: Hepatic ischemia reperfusion (HIR) injury is a major complication affecting various major liver surgeries, including liver transplantation. Aprepitant (APRE), a neurokinin-1 receptor antagonist, is commonly u...
BACKGROUND: Hepatic ischemia reperfusion (HIR) injury is a major complication affecting various major liver surgeries, including liver transplantation. Aprepitant (APRE), a neurokinin-1 receptor antagonist, is commonly used as an antiemetic to prevent chemotherapy-induced nausea and vomiting. AIM: To assess the potential protective effect of APRE against HIR-induced liver injury targeting the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing receptor 3/interleukin (IL)-1beta signaling pathway. METHODS: Six groups of adult male Wistar albino rats were divided as follows: Sham group, Sham/APRE10 group (APRE 10 mg/kg), HIR group, HIR/APRE5 group (APRE 5 mg/kg), HIR/APRE10 group (APRE 10 mg/kg), and HIR/APRE20 group (APRE 20 mg/kg). Serum alanine transaminase, aspartate transaminase, liver malondialdehyde, total antioxidant capacity levels, as well as IL-6, sirtuin 1 (Sirt1), caspase-3, cleaved caspase-3, and tumor necrosis factor alpha biomarkers, were evaluated. Hepatic specimens were examined histopathologically and immunohistochemically for nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression. RESULTS: HIR resulted in hepatic damage, as evidenced by histopathological changes and a significant increase in serum alanine transaminase, aspartate transaminase, hepatic malondialdehyde, caspase-3, and tumor necrosis factor alpha levels. Additionally, there were significant increases in hepatic total antioxidant capacity and reductions in IL-6 and cleaved caspase-3 protein levels, as demonstrated by Western blot analysis, along with enhanced immunoexpression of Sirt1 and Nrf2. APRE has significantly reduced various parameters of oxidative stress, inflammation, and apoptosis, and a significant increase in liver Nrf2 immunoexpression, leading to a significant improvement in the histopathological changes. CONCLUSION: In conclusion, targeting the Sirt1/Nrf2 signaling pathway, as demonstrated by APRE in our model, could present a promising therapeutic target to protect against HIR-induced liver injury during major liver surgeries.
Integrated serum metabolomics reveal molecular mechanism of Xietu Hemu prescription on metabolic dysfunction-associated steatotic liver disease-related obesity.
Cheng Z, Lu YF, He YX … +7 more , Wei W, Xie YX, Lv TS, Wei Y, Lou Y, Yu JY, Zhou XQ
World J Hepatol · 2025 Dec · PMID 41479521 · Full text
BACKGROUND: Xietu Hemu prescription (XHP), a Chinese patent formula, is optimized based on the theory of "phlegm-dampness" and has been clinically validated to effectively combat metabolic dysfunction-associated steatoti...
BACKGROUND: Xietu Hemu prescription (XHP), a Chinese patent formula, is optimized based on the theory of "phlegm-dampness" and has been clinically validated to effectively combat metabolic dysfunction-associated steatotic liver disease (MASLD). It notably reduces visceral fat and body mass index. However, the molecular mechanisms underlying its regulation of lipid metabolism homeostasis remain unexplored. AIM: To elucidate the mechanisms by which XHP inhibits adipocyte differentiation and maintains lipid metabolism homeostasis. METHODS: The therapeutic efficacy of XHP in metabolic-related disorders was analyzed using HepG2 cells and 3T3-L1 cells, along with transcriptomics to assess gene expression alterations during white adipogenesis. The primary metabolites of XHP were identified through ultra-performance liquid chromatography, and metabolic pathways were examined serum metabolomics. Network analysis was employed to predict therapeutic targets. The accumulation of lipid droplets and the expression of associated proteins were confirmed using oil red O staining and Western blotting, respectively. Molecular docking was utilized to identify core targets and signaling pathways, which were substantiated through immunofluorescence and siRNA interference. RESULTS: XHP-containing serum (XHPS) significantly inhibited the transformation of normal HepG2 cells into fatty liver cells. Concurrently, the treatment suppressed the differentiation of 3T3-L1 cells, reduced lipid droplet accumulation and total cholesterol/triglyceride levels, and downregulated the expression of PPARγ, C/EBPα, and FABP4. Through transcriptomics and network pharmacological intersectionality analyses, 24 core targets were identified, predominantly enriched in the AMPK signaling pathway. Molecular docking validated the strong binding affinity of XHP metabolites to targets such as leptin (-11.3 kcal/mol) and ADIPOQ (-9.4 kcal/mol). ELISA results indicated that XHPS augmented leptin autocrine secretion, thereby activating the AMPK signaling pathway ( < 0.05). Conversely, knockdown negated this effect ( < 0.05). CONCLUSION: XHP effectively inhibits adipogenesis and enhances lipid metabolism homeostasis through the LEP/AMPK/PPARγ pathway, presenting a promising multi-target therapeutic strategy for MASLD by mitigating lipotoxicity.
Steatotic liver disease in patients with chronic hepatitis C.
Janczura J, Brzdęk M, Flisiak R … +4 more , Dobrowolska K, Brzdęk K, Rzymski P, Zarębska-Michaluk D
World J Hepatol · 2025 Dec · PMID 41479520 · Full text
BACKGROUND: Steatotic liver disease (SLD) including metabolic dysfunction-associated SLD is the most prevalent chronic liver disease worldwide and is strongly associated with metabolic dysfunction as well as chronic hepa...
BACKGROUND: Steatotic liver disease (SLD) including metabolic dysfunction-associated SLD is the most prevalent chronic liver disease worldwide and is strongly associated with metabolic dysfunction as well as chronic hepatitis C (CHC). AIM: To compare the characteristics of patients with CHC virus infection and the treatment with direct-acting antivirals (DAAs), considering the presence of SLD comorbidity. METHODS: The study included all consecutive hepatitis C virus-infected patients treated with pangenotypic DAA regimens at a single tertiary hepatology center in 2018-2024. SLD was diagnosed abdominal ultrasound. RESULTS: Among 688 patients included in the study, 290 (42.2%) had comorbid SLD. The highest prevalence (62.3%) was observed in patients infected with genotype 3. The SLD group was predominantly male (62.8%), in contrast to the non-SLD group, where women predominated. Patients with SLD were significantly older ( = 0.0007), had a higher body mass index ( < 0.0001), and more frequently presented with diabetes ( = 0.01), obesity ( < 0.0001), hyperlipidemia ( = 0.004), and a history of alcohol abuse ( < 0.0001). They also had more advanced liver disease as indicated by a higher rate of cirrhosis (35.5% 12% in the non-SLD group, < 0.0001), elevated aminotransferase activity ( < 0.0001), bilirubin concentration ( < 0.0001), and international normalized ratio values ( = 0.0001), and lower albumin concentration ( = 0.0028). While most patients in both groups completed treatment as planned, adverse events, including severe events and deaths, were more frequent in the SLD group. A sustained virologic response was achieved in 97.6% of the overall population but was significantly lower among patients with SLD compared to the non-SLD group (95.6% 99.0%, = 0.0081). However, logistic regression analysis did not identify SLD as an independent predictor of treatment failure. CONCLUSION: Comorbid SLD was common among CHC patients treated with DAAs and was associated with adverse baseline characteristics, including older age, higher body mass index, greater comorbidity burden, and more advanced liver disease. Although SLD patients achieved slightly lower rates of sustained virologic response, SLD itself was not an independent predictor of treatment failure. These findings suggest that poorer treatment outcomes in this subgroup are largely attributable to coexisting risk factors rather than SLD per se, highlighting the need for comprehensive management of metabolic and liver-related comorbidities to optimize antiviral therapy outcomes.
Cerebrospinal fluid pseudocyst presenting as ascites: A case report.
Quek SXZ, Ching KWJ, Mangat K … +2 more , Low HC, Ko SQ
World J Hepatol · 2025 Dec · PMID 41479519 · Full text
BACKGROUND: Cerebrospinal fluid (CSF) pseudocysts are uncommon complications of ventriculoperitoneal (VP) shunts, usually occurring within 3 weeks to 10 years of insertion. We report a perihepatic CSF pseudocyst presenti...
BACKGROUND: Cerebrospinal fluid (CSF) pseudocysts are uncommon complications of ventriculoperitoneal (VP) shunts, usually occurring within 3 weeks to 10 years of insertion. We report a perihepatic CSF pseudocyst presenting over 27 years after shunt placement, representing an exceptionally long interval compared with prior reports. This case highlights the importance of maintaining diagnostic openness when investigating unexplained ascites, and demonstrates the role of fluid beta-2 transferrin in confirming a rare diagnosis. CASE SUMMARY: A 42-year-old man with spina bifida and prior VP shunt insertion was admitted for urinary tract infection, later developing recurrent symptomatic perihepatic fluid collections. Extensive hepatic, cardiac, and surgical evaluations were unremarkable, and repeated percutaneous drainages failed. The possibility of CSF origin was raised after clinical reappraisal, and beta-2 transferrin testing of the drained fluid confirmed a CSF pseudocyst. The patient underwent VP shunt exploration and revision with relocation to the pleural space, leading to resolution of the abdominal collections and symptoms. CONCLUSION: Persistent diagnostic uncertainty requires broad clinical suspicion and selective testing to identify rare causes of ascites.
Transcriptome profiles of peripheral blood mononuclear cells differentiate male adolescents with non-alcoholic fatty liver disease from healthy peers.
Zeber-Lubecka N, Michalkiewicz J, Dabrowska M … +9 more , Goryca K, Wierzbicka-Rucińska A, Jańczyk W, Jankowska I, Świąder-Leśniak A, Kubiszewska I, Ziemska-Legięcka J, Socha P, Ostrowski J
World J Hepatol · 2025 Dec · PMID 41479518 · Full text
BACKGROUND: Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells (PBMCs) that are associated with infectious, autoimmune, and inflammatory disorders, including chronic liver d...
BACKGROUND: Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells (PBMCs) that are associated with infectious, autoimmune, and inflammatory disorders, including chronic liver diseases. AIM: To identify potential differences in the transcriptome profiles of PBMCs between male patients with non-alcoholic fatty liver disease (NAFLD) and healthy male adolescents. METHODS: PBMCs were isolated from 16 male adolescents with NAFLD and 14 healthy age-matched male peers. The collected cells were cultured for 18 hours without and with autologous fecal extracts (FEs). Differentially expressed genes (DEGs) were investigated using RNA sequencing. Levels of interleukin (IL)-6, tumor necrosis factor-α, IL-10, and IL-1β secreted into the culture medium were determined using enzyme-linked immunosorbent assays. DEGs were functionally analyzed through annotation according to the Gene Ontology and Reactome databases. RESULTS: In total, 151 (118 protein-coding) and 97 (65 protein-coding) DEGs were identified when the RNA profiles of PBMCs stimulated without and with FEs, respectively, were compared between NAFLD patients and controls. Functional enrichment analysis of DEGs identified several pathways, which were predominantly involved in metabolism and inflammatory responses in non-stimulated and FE-stimulated PBMCs, respectively. FEs increased secretion of IL-6 and IL-1β by PBMCs isolated from controls and of all four cytokines by PBMCs isolated from NAFLD patients. IL-1β secretion was significantly higher in FE-stimulated PBMCs isolated from NAFLD patients than in those isolated from controls. CONCLUSION: Our data suggest that changes in PBMC gene expression may provide candidate biomarkers for NAFLD development, which require validation in larger cohorts.
Interplay between intestinal permeability and metabolic dysfunction-associated steatotic liver disease: Could there be a role for extra virgin olive oil consumption?
Giannitrapani L, Ferraro M, Seidita A … +2 more , Licata A, Soresi M
World J Hepatol · 2025 Dec · PMID 41479517 · Full text
Metabolic dysfunction-associated steatotic liver disease is a multifaceted disease associated with obesity, insulin resistance (IR), type 2 diabetes mellitus - in a word, metabolic syndrome - which has been extensively s...
Metabolic dysfunction-associated steatotic liver disease is a multifaceted disease associated with obesity, insulin resistance (IR), type 2 diabetes mellitus - in a word, metabolic syndrome - which has been extensively studied because it is related to an alteration of the normal metabolism of glucose and lipids, ultimately leading to triglyceride accumulation within hepatocytes. This lipid overload triggers an inflammatory status, also influenced by gut-liver axis dysfunction, with gut dysbiosis, which alters intestinal permeability, causing inflammation and IR in a vicious circle. Several approaches have been attempted to treat this condition and stop its possible evolution towards increasingly serious stages, but the first step is always lifestyle modification. The Mediterranean diet seems to be the most reliable for affecting liver steatosis, probably thanks to extra virgin olive oil, a healthy food with a high content of monounsaturated fatty acids and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol and tyrosol. This review investigates the mechanisms underlying the bidirectional and synergistic relationships among metabolic dysfunction-associated steatotic liver disease, IR, and the gut-liver axis, specifically focusing on the role of extra virgin olive oil as one of the main antioxidant components of the Mediterranean diet.
Drug-induced liver injury in inflammatory bowel disease: Challenges in diagnosis and monitoring.
Singh A, Bhardwaj A, Kaur H … +3 more , Bawa A, Midha V, Sood A
World J Hepatol · 2025 Dec · PMID 41479516 · Full text
Drug-induced liver injury (DILI) is an important but often underrecognized complication in the management of inflammatory bowel disease (IBD), particularly in patients receiving long-term immunomodulatory or biologic the...
Drug-induced liver injury (DILI) is an important but often underrecognized complication in the management of inflammatory bowel disease (IBD), particularly in patients receiving long-term immunomodulatory or biologic therapies. Agents such as thiopurines, methotrexate, anti-tumor necrosis factor agents, and newer small molecules including tofacitinib and upadacitinib have all been implicated in hepatotoxicity, with clinical manifestations ranging from asymptomatic elevations in liver enzymes to severe hepatic injury. Differentiating DILI from hepatobiliary disorders commonly associated with IBD, such as primary sclerosing cholangitis, metabolic dysfunction-associated steatotic liver disease, and autoimmune hepatitis, remains a significant diagnostic challenge. The absence of standardized monitoring protocols, coupled with the variable latency and heterogeneous presentation of DILI, further complicates early recognition and management. In this narrative review, we synthesize current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of DILI in IBD. We also outline diagnostic strategies, including the role and limitations of causality assessment tools, and propose practical considerations for baseline evaluation, longitudinal monitoring, and therapeutic decision-making.
Albumin-bilirubin score as a practical tool for prognostication in metabolic-associated steatotic liver disease.
Lee CW
World J Hepatol · 2025 Dec · PMID 41479515 · Full text
Metabolic-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, yet reliable tools for prognostication remain limited. Fibrosis-based indices such as the fibrosis-4 a...
Metabolic-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, yet reliable tools for prognostication remain limited. Fibrosis-based indices such as the fibrosis-4 and nonalcoholic fatty liver disease fibrosis score are widely used but primarily reflect structural damage rather than functional decline. The albumin-bilirubin (ALBI) score, originally established to assess hepatic reserve in patients with hepatocellular carcinoma, provides a simple and objective measure of liver function derived from routine laboratory parameters. Recent validation and meta-analytic studies have shown that ALBI predicts liver-related outcomes and all-cause mortality across diverse chronic liver disease populations, including MASLD, and offers complementary prognostic information beyond fibrosis-based models. Its simplicity, cost-effectiveness, and compatibility with automated reporting systems make it feasible for integration into clinical workflows and population-level risk stratification. However, interpretation of ALBI should consider potential confounders such as renal dysfunction, inflammation, and Gilbert syndrome, and threshold calibration across ethnic groups remains necessary. The ALBI score represents a promising functional biomarker that could enhance risk prediction and care pathways in MASLD, although prospective, multiethnic, and longitudinal studies remain needed to confirm its prognostic value and define clinically meaningful cut-offs.
Ultrasound imaging in orthotopic hepatocellular carcinoma models: Promise, practicality, and points for refinement.
Ghosh D, Kumar A
World J Hepatol · 2025 Dec · PMID 41479514 · Full text
The study by Devan presents an ultrasound-based protocol for monitoring tumor growth in a syngeneic orthotopic rat model of hepatocellular carcinoma (HCC). This approach is commendable for its reproducibility, cost-effe...
The study by Devan presents an ultrasound-based protocol for monitoring tumor growth in a syngeneic orthotopic rat model of hepatocellular carcinoma (HCC). This approach is commendable for its reproducibility, cost-effectiveness, and alignment with ethical imperatives, particularly in reducing the need for invasive assessments. The strong correlation of ultrasound-based volumes with histology and therapeutic response highlights its translational promise. However, certain considerations merit further discussion. Ultrasound imaging, while accessible, is inherently operator-dependent, and its accuracy may decline with irregular or heterogeneous tumor morphology. Moreover, the exclusive reliance on the rat hepatoma cell line (N1S1) cells raises questions about generalizability to other HCC models with differing immune interactions. Future refinements should standardize training protocols, incorporate multimodal validation, and explore diverse tumor settings. Despite these limitations, the study provides a useful approach, and its broader integration could democratize preclinical oncology research, especially in resource-constrained environments.
Microplastics in metabolic dysfunction-associated steatotic liver disease: An emerging threat to liver health.
Rajak S, Shahi A, Yadav A … +2 more , Medhe P, Sinha RA
World J Hepatol · 2025 Dec · PMID 41479513 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as non-alcoholic fatty liver disease, is a major cause of end-stage liver disease worldwide. Numerous studies have demonstrated that...
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as non-alcoholic fatty liver disease, is a major cause of end-stage liver disease worldwide. Numerous studies have demonstrated that the liver is predominantly influenced by environmental and lifestyle risk factors that lead to obesity and diabetes, excessive alcohol consumption, and exposure to environmental pollutants. Microplastics (MPs) are a significant global concern, having been detected in human blood, lungs, kidneys, and liver, and may have deleterious effects on these tissues. Although the effects of MP exposure on the liver have only been partially elucidated, further research is necessary to integrate the direct and extrahepatic effects of MPs on the pathogenesis of MASLD. This review offers a comprehensive analysis of the impact of MPs on hepatic metabolism, including their effects on mitochondrial homeostasis and the endocrine system, with potential implications for the progression of MASLD.
Severe hyperlipidemia associated with drug-induced cholestatic liver disease: A case report.
Xu MJ, Wei X, Lu Y … +3 more , Sun L, Xie Y, Li MH
World J Hepatol · 2025 Dec · PMID 41479512 · Full text
BACKGROUND: The global incidence of hyperlipidemia has been increasing on an annual basis, concomitant with improvements in living standards and dietary changes. Hyperlipidemia is closely associated with the development...
BACKGROUND: The global incidence of hyperlipidemia has been increasing on an annual basis, concomitant with improvements in living standards and dietary changes. Hyperlipidemia is closely associated with the development of numerous diseases, and in clinical cases, drug-induced cholestasis may lead to elevated serum cholesterol and triglyceride levels, a phenomenon known as secondary hyperlipidemia. Hyperlipidemia is recognized as a significant risk factor for the development of cardiovascular disease. Therefore, effective monitoring and control of lipid levels is crucial in the management of patients diagnosed with drug-induced cholestatic liver disease. CASE SUMMARY: We present a special case of refractory hyperlipidemia associated with cholestatic liver disease in a 49-year-old woman. CONCLUSION: In the treatment of clinical cases of drug-induced cholestatic liver disease and hyperlipidemia, it is essential for medical professionals to consider the patient's overall condition, formulate an individualized treatment plan, and closely monitor the patient's biochemical indices and clinical symptoms to ensure treatment efficacy and prognosis.
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