World J Hepatol [JOURNAL]
Sun
200 papers
Dynamic inflammation-based prognostication in acute-on-chronic liver failure: The COSSH-CAR model as a step forward in personalized risk stratification.
Ebrahim NAA, Farghaly TA, Soliman SMA
World J Hepatol · 2026 Feb · PMID 41809486 · Full text
Acute-on-chronic liver failure (ACLF) is a swiftly deteriorating condition characterized by profound systemic inflammation and failure of multiple organ systems, leading to high early mortality. There remains a critical...
Acute-on-chronic liver failure (ACLF) is a swiftly deteriorating condition characterized by profound systemic inflammation and failure of multiple organ systems, leading to high early mortality. There remains a critical need for more effective biomarkers to facilitate timely and accurate risk assessment. Recent findings by Zhu and Yan demonstrated that evaluating temporal changes in the C-reactive protein to albumin ratio (CAR), especially the 7-day variation, offers superior prediction of 28-day mortality compared with single baseline measurements. By integrating the 7-day variation of CAR with the model for end-stage liver disease sodium score and the grade of hepatic encephalopathy, the Chinese Group on Study of Severe Hepatitis B (COSSH)-CAR model was created, which surpassed traditional prognostic tools such as the Child-Pugh, model for end-stage liver disease, and COSSH-ACLF. This comment highlights the importance of using dynamic biomarker trajectories rather than static values for prognostic evaluation. CAR is biologically compelling because it captures both the inflammatory burden and the patient's nutritional/physiological reserve. While the COSSH-CAR model is promising and based on routinely obtainable laboratory data, its widespread adoption will depend on validation in larger, diverse, and non-hepatitis B virus-related cohorts. Future work should examine CAR kinetics in prospective and interventional studies and consider how they may support individualized management strategies. Collectively, these observations suggest that the CAR could represent an important addition to current ACLF prognostic frameworks.
Epstein-Barr virus infection in children with liver transplantation.
Onpoaree N, Leelakanok N, Sanpavat A … +1 more , Sintusek P
World J Hepatol · 2026 Feb · PMID 41809485 · Full text
Epstein-Barr virus (EBV) infection commonly occurs in children, particularly in developing countries. Most children infected with EBV are asymptomatic, though some develop significant complications, including EBV-associa...
Epstein-Barr virus (EBV) infection commonly occurs in children, particularly in developing countries. Most children infected with EBV are asymptomatic, though some develop significant complications, including EBV-associated malignancies, hemophagocytic lymphohistiocytosis, and multiple sclerosis. In immunocompromised children, including those with liver transplantation, EBV infection manifests with a diverse spectrum of presentations, varying from asymptomatic to post-transplant lymphoproliferative disorder, which can evolve into lymphoma. Therefore, close monitoring, early detection, and prompt management are crucial. This review aimed to investigate the pathogenesis and manifestations of EBV in healthy children and those who underwent liver transplantation. The proposed algorithm for early EBV detection and management, along with case studies, is provided to help pediatricians increase their index of suspicion.
Effects of tenofovir amibufenamide and entecavir on estimated glomerular filtration rate in treatment-naïve patients with chronic hepatitis B.
Ma SP, Wang L, Zhang YL … +5 more , Wan X, Liu Q, Tang YL, Malhi LR, Ge SF
World J Hepatol · 2026 Feb · PMID 41809484 · Full text
BACKGROUND: As a novel antiviral agent, the comparative renal safety of tenofovir amibufenamide (TMF) entecavir (ETV) in chronic hepatitis B (CHB) remains unclear. AIM: To compare changes in the estimated glomerular fil...
BACKGROUND: As a novel antiviral agent, the comparative renal safety of tenofovir amibufenamide (TMF) entecavir (ETV) in chronic hepatitis B (CHB) remains unclear. AIM: To compare changes in the estimated glomerular filtration rate (eGFR) between TMF and ETV in previously untreated patients with CHB over 48 weeks. METHODS: We retrospectively analyzed clinical records of 187 treatment-naive patients with CHB receiving TMF or ETV for ≥ 48 weeks from June 2021 to January 2025. Patients were allocated to the TMF ( = 48) or ETV ( = 139) group based on their antiviral drug therapy. Propensity score matching (2:1) was used to balance baseline clinical characteristics. eGFR changes at 48 weeks were compared. Patients were then stratified into normal and abnormal eGFR groups, and factors associated with abnormal eGFR were analyzed. RESULTS: After propensity score matching, 48 patients and 96 patients were stratified into the TMF and ETV group, respectively. At baseline, the two groups had comparable clinical characteristics, with no significant differences ( > 0.05). Baseline eGFR values were 111.83 mL/minute/1.73 m for the TMF group and 112.50 mL/minute/1.73 m for the ETV group ( = 0.712). At week 48, eGFR declined in both groups, but the ETV group experienced a significantly greater reduction relative to the TMF group (106.10 mL/minute/1.73 m 111.01 mL/minute/1.73 m; = 0.019). In univariate analysis, the groups differed significantly in terms of age, serum albumin, triglyceride, and baseline eGFR (all < 0.05). Multivariate analysis identified baseline eGFR and triglyceride as independent predictors of abnormal eGFR by 48 weeks ( < 0.05). CONCLUSION: In treatment-naïve patients with CHB, ETV treatment exhibited a strong association with an increased risk of decreased eGFR levels at 48 weeks in comparison with TMF.
Fatigue and circadian rhythm in non-cirrhotic primary biliary cholangitis: An exploratory comparison with primary sclerosing cholangitis and healthy controls.
Curto A, Tanturli M, Iamello RG … +8 more , Rossi P, Mengozzi G, Dei L, Mello T, Innocenti T, Dragoni G, Galli A, Lynch EN
World J Hepatol · 2026 Feb · PMID 41809483 · Full text
BACKGROUND: Fatigue is common and debilitating in primary biliary cholangitis (PBC) without clear relation to disease stage; mechanisms remain unclear. Circadian disruption is reported in end-stage liver disease, but evi...
BACKGROUND: Fatigue is common and debilitating in primary biliary cholangitis (PBC) without clear relation to disease stage; mechanisms remain unclear. Circadian disruption is reported in end-stage liver disease, but evidence in non-cirrhotic PBC, and links to fatigue, is scarce. AIM: To investigate the severity and phenotype of fatigue, daytime sleepiness, and chronotype in non-cirrhotic PBC, and compare findings with matched healthy controls (HC) and non-cirrhotic primary sclerosing cholangitis (PSC). METHODS: Participants completed the Fatigue Impact Scale, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire Self-Assessment. Demographics, sleep habits, employment, and fatigue subtype (mental muscular) were recorded. In PBC/PSC, PBC-40 fatigue/itch domains and disease characteristics were analyzed. Group comparisons and multivariable models evaluated associations of fatigue phenotype and chronotype with demographic/disease variables. RESULTS: We enrolled 152 individuals: 61 PBC, 30 PSC, and 61 HC. Global fatigue scores did not differ across groups. Muscular fatigue predominated in PBC/PSC, whereas HC more often reported mental fatigue; this pattern persisted after stratifying by employment and sex. In adjusted analyses, HC had lower odds of muscular fatigue than PBC [odd ratio (OR) = 0.30, 95% confidence interval (CI): 0.14-0.63; = 0.002]; PSC did not differ from PBC (OR = 1.25, 95%CI: 0.44-3.71; = 0.681). Older age independently increased the odds of muscular fatigue (OR = 1.04 per year, 95%CI: 1.01-1.07; = 0.016). Daytime sleepiness was low and similar between groups. Morningness-Eveningness Questionnaire Self-Assessment scores clustered in the intermediate range; age, not disease, predicted greater morningness. CONCLUSION: In non-cirrhotic PBC, fatigue shows a predominantly muscular phenotype independent of demographics/occupation and decoupled from conventional disease metrics. Chronotype and daytime alertness appear largely preserved, with age driving modest morningness. Findings support integrating fatigue phenotyping into assessment, prioritizing muscle-targeted interventions, and using carefully selected controls and objective endpoints in future studies.
Advances in biliary stone management: Latest-generation extracorporeal shock wave lithotripsy laser lithotripsy for difficult bile duct stones.
Singla N, Venkata KA, Inavolu P … +12 more , Memon SF, Koduri KK, Singh AP, Katamareddy T, Darisetty S, Koppoju V, Jagtap N, Kalpala R, Lakhtakia S, Ramchandani M, Tandan M, Reddy DN
World J Hepatol · 2026 Feb · PMID 41809482 · Full text
BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) and laser lithotripsy (LL) are established alternatives for the management of difficult common bile duct (CBD) stones. However, there is limited evidence regarding...
BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) and laser lithotripsy (LL) are established alternatives for the management of difficult common bile duct (CBD) stones. However, there is limited evidence regarding the efficacy and safety of the latest-generation Dornier Delta III lithotripter. In particular, evidence on the clinical performance of the Dornier Delta III lithotripter is scarce. AIM: To evaluate and compare the efficacy and safety of ESWL performed with the Dornier Delta III and of LL using a single-operator cholangioscope with specific focus on stone clearance rates, number of treatment sessions, and procedure-related adverse events in a large patient cohort. METHODS: We conducted a retrospective analysis of a prospectively maintained database at AIG Hospitals, Hyderabad, covering the period from January 2019 to December 2022. A total of 458 patients with difficult bile duct stones underwent either ESWL or LL based on clinical discretion. ESWL was performed using the Dornier Delta III lithotripter, whereas LL was carried out with a single-operator cholangioscope in combination with an yttrium-aluminum-garnet laser. RESULTS: The 387 patients with difficult bile duct stones (mean age 53.8 ± 15.7 years, 58.7% male) underwent ESWL. A single CBD stone was noted in 46.8% of patients while 53.2% patients had multiple stones. Complete duct clearance was achieved in 95.1% of patients, with 68.7% requiring two or more ESWL sessions. Adverse events included cholangitis in 3 patients and post-sphincterotomy bleeding in 4 patients; All were managed conservatively. Seventy-one patients (mean age 55 ± 15.4 years, 64.8% male) underwent LL. Complete duct clearance was achieved in 97.2% of patients with single-session clearance in 58 (81.7%) patients. The remaining 18.3% of patients required two or three sessions for fragmented stone removal. Adverse events included cholangitis in 2 patients and mild pancreatitis in 1 patient; all were managed conservatively. Patients with incomplete clearance were referred for surgery. There was no significant difference in efficacy between ESWL and LL (95.1% 97.2%, = 0.4). CONCLUSION: ESWL using the latest generation lithotripter and LL provide equally effective and safe alternatives for managing difficult CBD stones, minimizing the need for surgery.
Should the routine use of the 6-minute walk test be implemented in liver disease assessment: Not so fast.
Diaz-Cordova ME, Sharma I, Pascal W … +1 more , Okumura K
World J Hepatol · 2026 Feb · PMID 41809481 · Full text
End-stage liver disease (ESLD) is a debilitating condition that often leads to death. Once diagnosed with ESLD, a patient's quality of life decreases significantly. Well-established markers, such as the model for end-sta...
End-stage liver disease (ESLD) is a debilitating condition that often leads to death. Once diagnosed with ESLD, a patient's quality of life decreases significantly. Well-established markers, such as the model for end-stage liver disease and Child-Pugh scores, are used to diagnose, monitor, and predict survival. Another tool, the 6-minute walk test (6MWT), has shown promise as an adjunct measure but remains underutilized despite its strong results and ease of reproducibility. Previous research has demonstrated that the 6MWT, as in many other conditions, helps predict survival, mortality, and outcomes in individuals with ESLD. A recent observational study by Corrêa found that the 6MWT is a reliable measure of functional capacity in patients with liver cirrhosis. Although the study's small sample size of 20 patients limits its generalizability, the findings align with prior evidence showing that the 6MWT is an independent predictor of mortality and that poor test performance is associated with greater liver dysfunction. However, the 6MWT is a nonspecific test, and patient performance can be influenced by comorbidities such as heart failure, pulmonary disease, and frailty. Additionally, the optimal timing for administering the test has not been clearly established in the literature. Overall, although well-validated markers already exist for diagnosing and assessing outcomes in liver disease, the addition of the 6MWT-a low-cost, reliable, easily reproducible, and objective measure-may provide valuable prognostic and functional information if standardized protocols and covariates are better controlled.
Dynamic immune response and its influencing factors in COVID-19 patients with non-alcoholic fatty liver disease: A cohort study.
Yan P, Li R, Yuan XY … +4 more , Wang Y, Lan LJ, Yu XP, Liu DF
World J Hepatol · 2026 Feb · PMID 41809480 · Full text
BACKGROUND: Dynamic alterations in lymphocyte subsets demonstrate significant correlations with clinical disease severity in patients with coronavirus disease 2019 (COVID-19). As the most prevalent chronic liver disease...
BACKGROUND: Dynamic alterations in lymphocyte subsets demonstrate significant correlations with clinical disease severity in patients with coronavirus disease 2019 (COVID-19). As the most prevalent chronic liver disease globally, non-alcoholic fatty liver disease (NAFLD) exhibits distinct chronic inflammatory and immunometabolic disturbances that may substantially affect immune response patterns in COVID-19 patients. Nevertheless, the characteristics of lymphocyte subset dynamics and their clinical implications in COVID-19-NAFLD remain to be fully elucidated. AIM: To characterize the dynamic changes in lymphocyte subsets among COVID-19 patients with NAFLD, in order to delineate their immunological profiles and inform clinical management strategies. METHODS: The cohort study compared lymphocyte subpopulations in 858 COVID-19 patients and 670 COVID-19-NAFLD patients at admission, discharge, and 2-week/4-week post-discharge follow-ups. RESULTS: Compared to COVID-19 patients without NAFLD, NAFLD-comorbid patients demonstrated persistently elevated CD3+CD4+ counts as well as lymphocyte counts and percentages at admission and at the 2-week and 4-week follow-ups post-discharge (all < 0.05). Among COVID-19-NAFLD patients, those aged ≥ 60 years had significantly lower CD3+ counts, CD3+CD4+ counts, CD3+CD8+ counts, lymphocyte counts and percentages, and CD19+ counts and percentages at all assessed time points (all < 0.05); significant liver fibrosis correlated with reduced CD3+CD4+ counts, CD3+CD8+ counts, and lymphocyte counts and percentages across all time points (all < 0.05); multimorbidity (≥ 3 comorbidities) exacerbated immune imbalance, marked by elevated CD3+CD4+ percentages and CD56+ counts at admission, increased CD3+CD4+ counts, lymphocyte counts, and CD19+ counts and percentages at discharge, as well as sustained increases in CD3+CD4+ counts at the 2-week follow-up and higher CD3+CD4+ percentages at the 4-week post-discharge follow-up (all < 0.05); and obesity and elevated liver enzymes were independently linked to higher CD3+CD4+ counts, CD19+ counts, and lymphocyte counts at all post-admission evaluations (from discharge through the 4-week follow-up) (all < 0.05). CONCLUSION: Age, liver fibrosis, comorbidities, obesity, liver enzyme abnormalities, vaccination status, low-density lipoprotein cholesterol, and hemoglobin A1c significantly modulate immune responses in COVID-19-NAFLD patients, warranting targeted clinical attention. Furthermore, patients with uncomplicated NAFLD (including lean NAFLD) also require particular clinical attention to mitigate risks of immune imbalance.
Educational video modules for alcohol use disorder: A scalable tool to bridge the treatment gap in hepatology.
Jin ZX, Sun NZ
World J Hepatol · 2026 Feb · PMID 41809479 · Full text
The prospective cohort study by Twohig evaluates the efficacy of a novel educational video module (EVM) in promoting treatment engagement and reducing alcohol use among hospitalized patients with alcohol-associated live...
The prospective cohort study by Twohig evaluates the efficacy of a novel educational video module (EVM) in promoting treatment engagement and reducing alcohol use among hospitalized patients with alcohol-associated liver disease (ALD). Analyzing 42 patients, the study demonstrates that exposure to the EVM significantly increased rates of both pharmacologic (50% 22%) and psychosocial (73.8% 44%) treatment within 30 days of discharge, while markedly reducing the return to alcohol use (7.9% 35.6%) compared to a retrospective control cohort. These findings underscore the potential of a standardized, scalable educational intervention to bridge critical knowledge gaps in alcohol use disorder (AUD) management. While the study highlights the EVM as a powerful tool for patient empowerment and system-level quality improvement, its single-center design and limited sample size necessitate further validation through multicenter randomized trials. This article contextualizes these promising results within the broader challenge of AUD treatment, emphasizing the urgent need to integrate innovative, patient-centered education into standard clinical pathways to alleviate the growing burden of ALD.
Qushi Huoxue ointment ameliorates metabolic associated steatotic liver disease through autophagy activation and ferroptosis inhibition.
Liu YY, Qin H, Wu HX … +6 more , Wang RT, Yang QY, Jiang F, Liu XD, Wu DK, Tang YM
World J Hepatol · 2026 Feb · PMID 41809478 · Full text
BACKGROUND: Metabolic associated steatotic liver disease (MASLD) has become a growing global health burden, with its potential to progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Qushi Huoxue ointment...
BACKGROUND: Metabolic associated steatotic liver disease (MASLD) has become a growing global health burden, with its potential to progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Qushi Huoxue ointment (QSHXO), a traditional Chinese medicine formula, has demonstrated efficacy in the management of MASLD. However, its underlying mechanisms remain incompletely elucidated. AIM: To investigate the mechanism by which QSHXO alleviated hepatic lipid deposition and inflammatory injury in MASLD, with a focus on its role in activating hepatocyte autophagy and inhibiting ferroptosis. METHODS: This study employed a comprehensive research strategy. First, a methionine-choline-deficient diet-triggered MASLD mouse model was established and treated with different doses of QSHXO. The therapeutic effects of QSHXO were comprehensively evaluated using histological analysis, serum biochemical assays, and inflammatory cytokine measurements. Subsequently, bioactive components of QSHXO in serum were identified utilizing liquid chromatography-tandem mass spectrometry. Network pharmacology was then applied to predict potential targets of QSHXO in treating MASLD related to autophagy and ferroptosis. These predicted targets were validated through western blotting, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and transmission electron microscopy. RESULTS: QSHXO significantly ameliorated liver lipid deposition and inflammation in MASLD mice. Specifically, QSHXO promoted autophagic flux, as indicated by upregulation of Beclin1, an increased light chain 3 II/light chain 3 I ratio, and downregulation of P62. Concurrently, QSHXO activated the nuclear factor erythroid 2-related factor 2 pathway, promoting its nuclear translocation and enhancing the expression of downstream targets (SLC7A11 and glutathione peroxidase 4), while reducing hepatic iron deposition; these collectively suggested suppression of ferroptosis. Ultrastructural analysis further confirmed improved mitochondrial morphology and increased autophagic vesicles in QSHXO-treated groups. CONCLUSION: QSHXO ameliorates MASLD by reducing lipid accumulation, mitigating inflammation, and suppressing hepatocyte damage, which is mediated through the activation of autophagy and inhibition of ferroptosis.
Transjugular intrahepatic portosystemic shunt improves survival in anticoagulation-resistant hepatic sinusoidal obstructive syndrome patients: A multicenter retrospective study.
Tu JJ, Zhang H, Kong DR … +11 more , Feng YH, Yu YC, Li TS, Zhang F, Zhang W, Xu H, Yin Q, Wang L, Zhang M, Xiao JQ, Zhuge YZ
World J Hepatol · 2026 Feb · PMID 41809477 · Full text
BACKGROUND: Anticoagulation therapy is recommended during the acute or subacute stage for patients with pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome (PA-HSOS). Transjugular intrahepatic portosystemic sh...
BACKGROUND: Anticoagulation therapy is recommended during the acute or subacute stage for patients with pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome (PA-HSOS). Transjugular intrahepatic portosystemic shunts (TIPS) is suggested as a step-up treatment when patients do not respond to anticoagulants. However, more evidence of the efficacy of TIPS is needed. AIM: To evaluate the effect of TIPS in these patients. METHODS: Between January 2013 and September 2020, we retrospectively enrolled patients with PA-HSOS who did not respond to short-term anticoagulation therapy at four hospitals. The patients were divided into a TIPS treatment group and an anticoagulation therapy group. Baseline information and clinical characteristics were collected and recorded. Survival in both groups was the primary study endpoint and the risk factors for patient death were further analyzed. RESULTS: A total of 99 patients were enrolled according to the inclusion and exclusion criteria (63 in the TIPS group and 36 in the anticoagulation therapy group). There were 17 deaths during the median follow-up time of 32.5 months. Treatment, age, aspartate aminotransferase, and serum total bilirubin were independent risk factors for predicting death. The survival of patients in the TIPS group was significantly greater than that of patients in the continuing anticoagulation therapy group ( = 0.028). When stratified by the Drum-Tower Severity Scoring, in the TIPS group, mild and moderate patients had better outcomes than severe patients. CONCLUSION: TIPS can improve the transplant-free survival rate in patients with PA-HSOS who do not respond to short-term anticoagulation therapy, and patients with mild and moderate Drum-Tower Severity Scoring grade can benefit from TIPS.
Adipokine profiles reflect metabolic dysfunction but not fibrosis in patients with primary biliary cholangitis.
Koky T, Drazilova S, Komarova S … +7 more , Macej M, Toporcerova D, Janicko M, Spakova I, Rabajdova M, Marekova M, Jarcuska P
World J Hepatol · 2026 Feb · PMID 41809476 · Full text
BACKGROUND: Primary biliary cholangitis (PBC) is a rare, nonsuppurative cholestatic disease that affects the small intrahepatic bile ducts. If not adequately managed, it may progress to liver cirrhosis and hepatocellular...
BACKGROUND: Primary biliary cholangitis (PBC) is a rare, nonsuppurative cholestatic disease that affects the small intrahepatic bile ducts. If not adequately managed, it may progress to liver cirrhosis and hepatocellular carcinoma. Only a few studies have explored the impact of cardiometabolic risk factors on liver fibrosis progression in PBC. Relevant data on the role of adipokines in these processes are also limited. AIM: To compare leptin and adiponectin levels in PBC patients stratified by the presence of metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic syndrome (MetS), fibrosis, and biochemical response. METHODS: We conducted a cross-sectional study involving 81 PBC patients diagnosed according to European Association for the Study of the Liver guidelines, all followed at a tertiary care center in Košice, Slovakia. Patients were included consecutively from the patient database in hepatology clinic in a prospective manner. Data on biochemical, clinical and anthropometric variables and their associations with MASLD, MetS, fibrosis, and biochemical response were evaluated using statistical methods including logistic regression and receiver operating characteristic analysis. RESULTS: Patients with PBC/MASLD had significantly lower adiponectin levels (1698.24 pg/mL 2042.08 pg/mL, = 0.015) and higher leptin levels (1.89 ng/mL 0.62 ng/mL, < 0.001) compared with those without MASLD. The leptin-to-adiponectin (L/A) ratio was also significantly elevated (1.63 0.27, < 0.001). Similar patterns were observed in patients with MetS: Adiponectin (1208.41 pg/mL 2086.10 pg/mL, = 0.002), leptin (1.51 ng/mL 0.79 ng/mL, = 0.002), and L/A ratio (1.28 0.41, = 0.009). By contrast, no significant differences in adipokine levels were observed between patients with and without advanced fibrosis or complete biochemical response (all > 0.05). CONCLUSION: Adipokines reflect metabolic status in PBC. The L/A ratio is promising biomarker for MASLD. No significant association between leptin and adiponectin levels and advanced fibrosis was detected within the limited sample size of this study.
Development and prospective validation of a machine learning model to predict mortality in cirrhosis with esophageal variceal bleeding.
Rech MM, Corso LL, Dal Bó EF … +7 more , Ferraza AD, Tomé F, Terres AZ, Balbinot RS, Balbinot RA, Balbinot SS, Soldera J
World J Hepatol · 2026 Feb · PMID 41809475 · Full text
BACKGROUND: Acute esophageal variceal bleeding (AEVB) is a critical complication in patients with cirrhosis, associated with high mortality despite advancements in management. Traditional prognostic scores often lack pre...
BACKGROUND: Acute esophageal variceal bleeding (AEVB) is a critical complication in patients with cirrhosis, associated with high mortality despite advancements in management. Traditional prognostic scores often lack predictive accuracy in this context. AIM: To develop, internally validate, and prospectively validate a machine learning (ML) model to predict 1-year mortality in patients with cirrhosis presenting with AEVB. METHODS: A retrospective cohort of 94 patients treated between 2010 and 2016 was used to train ML models, incorporating 36 clinical, laboratory, and imaging variables. Four algorithms (generalized linear models, boosted generalized linear models, naive Bayes, random forests) were evaluated, and the best-performing model was prospectively validated in a cohort of 24 patients treated between 2017 and 2018. Performance metrics included the area under the curve (AUC), sensitivity, specificity, and calibration Brier scores. Data preprocessing involved k-nearest neighbor imputation, one-hot encoding, and scaling. RESULTS: The random forest model achieved the highest AUC (0.91, 95% confidence interval [CI]: 0.85-0.96) during internal validation and demonstrated robust performance in the prospective cohort (AUC 0.88, 95%CI: 0.80-0.94). Calibration was excellent, with a low Brier score (0.12). The model was deployed as an online prediction tool. CONCLUSION: This ML model shows promise in improving mortality prediction for AEVB, potentially aiding timely clinical interventions and decision-making. Prospective validation underscores its generalizability and clinical utility. Future research should explore external validation in diverse settings.
Diagnostic challenges of clinically significant portal hypertension in geriatric metabolic dysfunction-associated fatty liver disease: A case report.
Akbar FN, Darnindro N, Wardhani AA … +6 more , Choirida SR, Saphira SN, Ismed G, Kshanti IAM, Mustika S, Hendarto H
World J Hepatol · 2026 Feb · PMID 41809474 · Full text
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) may progress to cirrhosis and lead to serious complications. Lipid accumulation, hepatocellular ballooning, and sinusoidal endothelial dysfunction...
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) may progress to cirrhosis and lead to serious complications. Lipid accumulation, hepatocellular ballooning, and sinusoidal endothelial dysfunction increase intrahepatic vascular resistance, resulting in early clinically significant portal hypertension (CSPH). Although hepatic venous pressure gradient (HVPG) remains the gold standard, decompensated cirrhosis may yield deceptively low values. Transient elastography and platelet count provide supportive diagnostic evidence, yet obesity can overestimate disease severity. This report highlights the diagnostic challenge of CSPH, especially MAFLD in geriatric patients. CASE SUMMARY: A 78-year-old woman with class I obesity, type 2 diabetes mellitus, and dyslipidemia presented with hematemesis and melena for a three-day period. A prior computed tomography scan revealed moderate diffuse hepatic steatosis, splenic vein dilatation, and splenomegaly. On admission, she presented with pallor, epigastric tenderness, splenomegaly, and mild ascites. Laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia, and hyperglycemia. Abdominal ultrasound confirmed chronic liver disease with splenomegaly. Esophagogastroduodenoscopy demonstrated grade II-III esophageal varices and portal hypertensive gastropathy. Noninvasive fibrosis assessments (non-alcoholic fatty liver disease fibrosis score, aspartate transaminase-to-platelet ratio index, fibrosis-4 index, and FibroScan: E = 28 kPa, controlled attenuation parameter = 191 dB/m) indicated advanced hepatic fibrosis. HVPG measurement was not performed, however due to the Baveno VII criteria (transient elastography ≥ 25 kPa and platelet count < 150 × 10/L), confirmed the diagnosis of CSPH. The patient received endoscopic variceal ligation, a nonselective beta-blocker, a proton pump inhibitor, insulin, a sodium-glucose cotransporter 2 inhibitor, and lifestyle modification, resulting in clinical improvement. CONCLUSION: Early and precise evaluation of CSPH in geriatric MAFLD requires an integrated clinical assessment to optimize diagnosis, management, and improve outcomes.
Should the theory of methotrexate-induced liver toxicity be abandoned?
Al-Hammada Y, Sharba S, Al-Dury S
World J Hepatol · 2026 Feb · PMID 41809473 · Full text
Methotrexate (MTX) remains a cornerstone therapy for chronic inflammatory diseases (, rheumatoid arthritis, psoriasis). However, long-standing concerns about MTX hepatotoxicity - especially liver fibrosis - have historic...
Methotrexate (MTX) remains a cornerstone therapy for chronic inflammatory diseases (, rheumatoid arthritis, psoriasis). However, long-standing concerns about MTX hepatotoxicity - especially liver fibrosis - have historically led to conservative monitoring and routine invasive liver biopsies at predefined cumulative dose thresholds. These practices often prompted early discontinuation of MTX therapy. These concerns originated from early liver biopsy studies in high-dose MTX patients that did not adequately account for metabolic risk factors. Emerging evidence indicates that advanced fibrosis is rare in MTX-treated patients and usually attributable to coexisting metabolic comorbidities (, obesity, insulin resistance) rather than the cumulative MTX dose itself. Moreover, noninvasive fibrosis assessment modalities and recent large cohort studies demonstrate that MTX at standard doses with folate supplementation seldom drives fibrogenesis independently. This review reappraises MTX-related fibrosis risk in light of contemporary data and highlights a shift from dose-driven biopsy protocols to risk-based, noninvasive monitoring strategies. Recognizing that MTX is less hepatotoxic than historically assumed can prevent unnecessary drug discontinuation and refocus management on modifiable metabolic risk factors.
Predictive tool for evident histological liver injury in chronic hepatitis B patients: Development and validation.
Dai ZS, Cao X, Jiang YF … +1 more , He B
World J Hepatol · 2026 Feb · PMID 41809472 · Full text
BACKGROUND: Chronic hepatitis B (CHB) is a leading cause of liver-related mortality, progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Existing noninvasive tools (, aspartate aminotransferase to platelet...
BACKGROUND: Chronic hepatitis B (CHB) is a leading cause of liver-related mortality, progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Existing noninvasive tools (, aspartate aminotransferase to platelet ratio index, fibrosis-4 index, liver stiffness measurement) and invasive liver biopsy have limitations in assessing evident histological liver injury (EHLI), highlighting the need for novel predictive models. AIM: To develop and validate a predictive model for EHLI in CHB patients using a cohort from Hunan Province, China, to facilitate early risk identification and optimize resource allocation. METHODS: This observational real-world study enrolled 223 CHB patients (August 2020 to March 2022) from the Second Xiangya Hospital, divided into development ( = 159) and validation ( = 64) cohorts (7:3 ratio). EHLI was defined as Ishak fibrosis stage ≥ 3 and/or histologic activity index ≥ 9. Variables were screened univariable logistic regression and least absolute shrinkage and selection operator regression, and a multivariable logistic regression model and nomogram were constructed. Performance was evaluated using area under the curve (AUC), calibration plots, Hosmer-Lemeshow test, and decision curve analysis (DCA). Gene expression profiles were analyzed to identify immune-related pathways. RESULTS: L59, platelet count (PLT), alanine transaminase (ALT), and aspartate transaminase (AST) were identified as independent predictors of EHLI. The model showed high discriminative ability, with AUC of 0.921 [95% confidence interval (CI): 0.880-0.963] in the development cohort and 0.959 (95%CI: 0.910-1.0) in the validation cohort, demonstrating a 20%-32% relative improvement in AUC over conventional noninvasive scores. Calibration plots demonstrated good agreement between predicted and observed EHLI, and DCA confirmed clinical utility (threshold probabilities: 20%-80%). Transcriptomic analysis identified 210 differentially expressed genes, with hub genes (, ) and transforming growth factor-β/Smad pathway involvement linked to liver injury. CONCLUSION: A novel nomogram incorporating L59, PLT, ALT, and AST robustly predicts EHLI in CHB patients. This model, using routinely measured variables, aids clinical decision-making and optimizes resource allocation.
as leading cause of pyogenic liver abscess: Three years study in Southern Vietnam.
Mai-Phan TA, Thai KP, Le KL … +6 more , Pham TN, Tran MQ, Pham PC, Duong NN, Trinh MT, Le NK
World J Hepatol · 2026 Feb · PMID 41809471 · Full text
BACKGROUND: Pyogenic liver abscess (PLA) is increasingly recognized worldwide. In Asia, () has emerged as the predominant pathogen, yet contemporary data from Vietnam remain limited. AIM: To determine the microbial spec...
BACKGROUND: Pyogenic liver abscess (PLA) is increasingly recognized worldwide. In Asia, () has emerged as the predominant pathogen, yet contemporary data from Vietnam remain limited. AIM: To determine the microbial spectrum of PLA and compare clinical, computed tomography (CT), management, and outcomes between and non- cases in Southern Vietnam. METHODS: This retrospective cohort included adults with PLA managed at Nhan Dan Gia Dinh Hospital from June 2021 to June 2024. Of 123 cases, 17 were excluded (8 with unspecified Gram-negative bacilli, 9 without CT), leaving 106 patients (83 , 23 non-). Data on demographics, comorbidities, presentation, laboratory, imaging, microbiology, treatment, and outcomes were analyzed using standard parametric/nonparametric and /Fisher tests (two-sided = 0.05). RESULTS: Mean age was 59.2 years, and 67.0% were male. Diabetes was more frequent in (55.4% 30.4%; = 0.034). C-reactive protein was higher in but not significant (229.9 mg/L 185.0 mg/L; = 0.069). Aspartate aminotransferase was significantly elevated ( = 0.048) and alanine aminotransferase borderline ( = 0.065). On CT, abscesses more often had irregular margins ( = 0.038) and heterogeneous architecture ( = 0.003). predominated in pus (71.9%) and blood (78.6%) cultures. Source-control and hospital stay were similar. Mortality was 10.4% overall, occurring only in (13.3% 0%). Older age predicted poorer survival (odds ratio = 0.95; = 0.029). CONCLUSION: In Southern Vietnam, predominates in PLA, characterized by distinctive CT features and higher mortality, emphasizing early recognition, pathogen-directed therapy, and timely image-guided drainage.
Performance of three clinical scores for steatosis and steatohepatitis and their interaction with metabolic syndrome in obese individuals.
Farina GS, Brambilla B, Pandolfo EM … +16 more , Lazzaretti LKN, Kuiava SMS, Graciolli AM, Kriger VM, Fistarol CHDB, Sgarioni AC, Giovanardi HP, Tregnago AC, Riva F, Scholze CDS, Agostini DC, Dellamea B, Tamayo A, Cerqueira TL, Soldera J, Illigens BM
World J Hepatol · 2026 Feb · PMID 41809470 · Full text
BACKGROUND: Non-invasive clinical scores are widely used to detect hepatic steatosis and steatohepatitis, but their accuracy in individuals with obesity is limited. Most of these tools were developed for non-obese popula...
BACKGROUND: Non-invasive clinical scores are widely used to detect hepatic steatosis and steatohepatitis, but their accuracy in individuals with obesity is limited. Most of these tools were developed for non-obese populations and do not account for metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum. Moreover, the potential modifying effect of metabolic syndrome (MetS) on the diagnostic performance of these scores remains unclear. Given the global burden of obesity and MASLD, there is a pressing need to refine diagnostic strategies for early detection. We hypothesized that diagnostic performance may vary by MetS status and can be improved with adjusted thresholds. AIM: To evaluate and optimize three clinical scores for steatosis and metabolic dysfunction-associated steatohepatitis (MASH), including assessment by MetS status. METHODS: This cross-sectional study included 95 individuals undergoing bariatric surgery at a hospital in Brazil. Clinical scores [non-alcoholic fatty liver disease liver fat score (NLFS), hepatic steatosis index (HSI), and fatty liver index (FLI)] were calculated from preoperative data. Liver biopsy was used as the reference standard to assess steatosis and MASH. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve, and optimal cut-offs were determined by Youden's index. Logistic regression with interaction terms assessed whether MetS modified the diagnostic performance of each score across histological outcomes. RESULTS: Sixty-six individuals (69.5%) had steatosis, and fifteen (15.8%) had moderate-to-severe steatosis and MASH. The area under the receiver operating characteristic curves for any steatosis was 0.676 (NLFS), 0.540 (HSI), and 0.468 (FLI); for moderate-to-severe steatosis, 0.671 (NLFS), 0.659 (HSI), and 0.700 (FLI); and for MASH, 0.671 (NLFS), 0.625 (HSI), and 0.639 (FLI). Standard cut-offs performed poorly; optimized thresholds improved both sensitivity and specificity. NLFS outperformed FLI for any steatosis ( = 0.021). No significant interactions were found between MetS and any score (all > 0.05), indicating that diagnostic accuracy did not significantly differ by MetS status. CONCLUSION: NLFS, HSI, and FLI show limited accuracy in obese individuals. Adjusting thresholds improves performance. Diagnostic utility remains consistent regardless of MetS, supporting their use across the MASLD spectrum.
Assessing the associations between immunosuppressant use and COVID-19 severity in patients with autoimmune hepatitis.
Rai K, Lindquist KJ, Kornak J … +1 more , Ge J
World J Hepatol · 2026 Feb · PMID 41809469 · Full text
BACKGROUND: Due to immunosuppression (IS) use, patients with autoimmune hepatitis (AIH) may be at high risk for poor coronavirus disease 2019 (COVID-19) outcomes. AIM: To investigate the associations between IS type and...
BACKGROUND: Due to immunosuppression (IS) use, patients with autoimmune hepatitis (AIH) may be at high risk for poor coronavirus disease 2019 (COVID-19) outcomes. AIM: To investigate the associations between IS type and COVID-19 severity in AIH patients using the National Clinical Cohort Collaborative (N3C) COVID enclave. METHODS: We identified all AIH patients with COVID-19 in the N3C COVID enclave. We used adjusted logistic regressions to determine associations between IS type and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We used Cox models to determine associations between IS type and all-cause mortality in the subset of AIH patients infected with SARS-CoV-2. RESULTS: Of 15187 AIH patients, 5106 (33%) had IS exposure, and 1604 (11%) tested positive for SARS-CoV-2 during the study period from March 2020 through March 2025. There was an association with prednisone [odds ratio (OR): 0.81, 95%CI: 0.65-0.99, = 0.04] exposure and SARS-CoV-2 test positivity. For interactions between different IS combinations and SARS-CoV-2 test positivity in the overall cohort, budesonide and azathioprine (OR: 1.88, 95%CI: 1.02-3.44, = 0.04) and prednisone and tacrolimus interactions (OR: 1.99, 95%CI: 1.14-3.53, = 0.02) showed significant associations. Within the subgroup finding of patients with full model for end stage liver disease data, budesonide and azathioprine interaction (OR: 4.44, 95%CI: 1.29-16.72, = 0.02) also had a significant association. In our adjusted Cox regressions and corresponding subgroup analysis, we found no specific IS type that was statistically significant in association with all-cause mortality. CONCLUSION: Prednisone exposure was negatively associated, and statistically significant IS interactions were positively associated with testing positive for SARS-CoV-2. Further work involves determining the impact of vaccinations and advances in COVID-19 treatment on outcomes in this population.
Environmental considerations in hepatitis E virus transmission: Is there a missing link?
Campbell R, Russell C, Izopet J … +5 more , Nassim K, Sonderup M, Pischke S, Wallace SJ, Madden RG
World J Hepatol · 2026 Feb · PMID 41809468 · Full text
Hepatitis E virus (HEV) is a zoonotic infection that varies according to genotype and geographical location. The full environmental and public health impact of hepatitis E remains uncertain. In this review, we aim to syn...
Hepatitis E virus (HEV) is a zoonotic infection that varies according to genotype and geographical location. The full environmental and public health impact of hepatitis E remains uncertain. In this review, we aim to synthesise the evidence regarding HEV circulation in the environment. A literature search was conducted regarding HEV transmission and findings in environmental context, and this was synthesised to propose a hypothesis and identify gaps in our current understanding. Environmental spillover occurs due to increased interactions at the human-animal-environmental interface, with multiple causative factors. HEV genotypes 3 and 4 have been documented in pigs, deer, chicken, rat, mongoose, rabbit, dolphin, cats, dogs and horses. Other HEV genotypes 1,2 and 5-7 have been found in bandicoot, musk shrew, mink, moose, fish and camel. HEV seropositivity has also been identified in ruminant species without HEV - related sequences being identified. HEV has been found in fruit, shellfish and crops irrigated with infected water. This leads to environmental contamination. HEV circulates in the environment the asymptomatic wild animal host with episodes of spillover into domestic animal populations with increasing burden within the everchanging 'virosphere'. Through domestic animal amplification, the spillover effect from both wild and domestic animal populations leads to human amplification causing disease with high morbidity and mortality in certain patient populations. Further research is required to consider the viral determinants for HEV cross-species infection and how this relates to HEV-contaminated food products and its impact on environment and human health.
Levodopa: A novel therapeutic prospect for liver disease.
Xu J, Qian Y, Wang JM … +2 more , Wu XL, Zheng YY
World J Hepatol · 2026 Feb · PMID 41809467 · Full text
In this article, we discuss the recently published study by Wang , which investigated the therapeutic potential of levodopa, a well-known drug used to treat Parkinson's disease, for the treatment of liver diseases. The s...
In this article, we discuss the recently published study by Wang , which investigated the therapeutic potential of levodopa, a well-known drug used to treat Parkinson's disease, for the treatment of liver diseases. The study revealed that levodopa, a dopamine precursor, exerts therapeutic effects by modulating dopamine receptor D1 signaling and activating Hippo/Yes-associated protein 1 pathway, which plays an important role in liver fibrosis. Furthermore, given that dysregulation of the brain-liver axis, including the dopaminergic reward circuit, has been implicated in the progression of liver diseases, particularly those exacerbated by stress, the purpose of this article is to make a further investigation on the potential of levodopa in regulating metabolic dysfunction and addressing maladaptive eating behaviors. Considering the important role of dopamine in regulating lipid metabolism, inflammation, and fibrosis in the liver, levodopa may present as a promising therapeutic candidate for chronic liver diseases characterized by altered dopamine sensitivity.
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