International Journal Of Hepatology[JOURNAL]
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200 papers
Incidence of Adverse Cardiac Events After Liver Transplantation in Patients With Different Hemodynamic Classifications of Pulmonary Hypertension.
Wang DW, Katayama A, Ligon MM … +3 more , Crowley SE, Sathe AM, Abuelkasem E
Int J Hepatol · 2026 · PMID 42368181 · Full text
INTRODUCTION: Pulmonary hypertension (PH) in liver transplantation candidates is associated with elevated morbidity and mortality. Few studies have investigated whether different categories of PH based off hemodynamic ch...
INTRODUCTION: Pulmonary hypertension (PH) in liver transplantation candidates is associated with elevated morbidity and mortality. Few studies have investigated whether different categories of PH based off hemodynamic characteristics portend worse outcomes. Furthermore, there have been newly defined parameters for PH classifications. Therefore, we aimed to compare postoperative outcomes after liver transplantation in patients within different newly established hemodynamic categories of PH. METHODS: This was a 20-year single-center retrospective observational study of adult patients undergoing liver transplantation. Patients with a diagnosis of PH and confirmatory right heart catheterization (RHC) were included in the study. Based off pulmonary artery wedge pressure (PAWP) and Wood units (WU), patients were categorized into four groups: precapillary (PrePH), isolated postcapillary (IpcPH), combined postcapillary (CpcPH), unclassified (UncPH). Our primary outcome was a composite of adverse cardiac events within 30 days postoperatively. Secondary outcomes included prolonged ventilation, acute kidney injury, and mortality at 30 days, 6 months, and 1 year. RESULTS: Of the 2409 patients who underwent liver transplantation in the study period, 80 patients met criteria for inclusion. The incidences of ACEs were 0% in PrePH, 31.4% in IpcPH, 25.0% in CpcPH, and 10.3% in UncPH ( = 0.04). Patients with postoperative ACEs had elevated PAWP (18.1 vs. 14.0 mmHg, = 0.01) and lower pulmonary vascular resistance (0.79 vs 1.3 WU, = 0.01). There were no differences observed in secondary outcomes. CONCLUSION: In this single-center study, we observed that patients with isolated precapillary PH did not have adverse cardiac events. Instead, patients with elevated PAWP, indicating postcapillary PH, were more likely associated with adverse cardiac events. This observation is seen despite milder pulmonary disease, as intended by newly established definitions for PH. Further investigation is warranted, as there may be prognostic implications that can drive future guidelines for liver transplantation in patients with PH.
SGLT-2 Inhibitors for Ascites Management in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Available Evidence.
Al Ghnaimat A, Ahmed NAT, Al-Azzawi OM … +10 more , Ibrahim EA, Rayyan R, Alkloub S, Al Joufi E, Breish EE, Shaik S, Al-Kadhimi N, Al Masalha B, Abdelbaqi H, Abouda DA
Int J Hepatol · 2026 · PMID 42358872 · Full text
GOAL: The goal is to systematically evaluate the efficacy and safety of SGLT-2 inhibitors (SGLT2i) versus standard therapy for ascites management in liver cirrhosis. BACKGROUND: SGLT2i promote natriuresis and osmotic diu...
GOAL: The goal is to systematically evaluate the efficacy and safety of SGLT-2 inhibitors (SGLT2i) versus standard therapy for ascites management in liver cirrhosis. BACKGROUND: SGLT2i promote natriuresis and osmotic diuresis, offering potential therapeutic benefits for fluid overload in cirrhosis, similar to their established role in heart failure. However, high-quality comparative evidence remains limited. STUDY: A systematic search of PubMed, Scopus, Cochrane, Embase, and Web of Science was conducted through October 2025 following PRISMA 2020 guidelines. Eligible studies included randomized controlled trials and prospective comparative studies enrolling adults (≥ 18 years) with confirmed cirrhosis treated with dapagliflozin or empagliflozin, alone or alongside standard therapy, versus placebo or standard care for ≥ 2 weeks. The primary outcome was complete ascites resolution; secondary outcomes included mortality, body weight, eGFR, and serum creatinine and sodium levels. RESULTS: Three studies (two RCTs and one prospective trial; = 382) were included, comprising 241 patients receiving SGLT2i and 141 controls. SGLT2i significantly increased complete ascites resolution (OR: 2.39, 95% CI: 1.47-3.90; < 0.001; = 15) and reduced body weight (MD: -4.86 kg, 95% CI: -7.57 to -2.14; = 0.0005; = 0). No significant differences were observed in eGFR, serum creatinine, serum sodium, or mortality within the RCT subgroup (OR: 1.60, 95% CI: 0.53-4.87; = 0); the overall three-study pool (OR: 0.27, 95% CI: 0.13-0.56; = 87) was driven by the nonrandomized trial (test for subgroup differences = 0.001). The only placebo-controlled RCT reported significantly higher rates of AKI (50% vs. 15%, = 0.04) and infections (55% vs. 20%, = 0.04) in the SGLT2i arm. CONCLUSIONS: SGLT2i improved ascites resolution and body weight without changes in routinely measured renal parameters, but unresolved AKI and infection signals and very low GRADE certainty for mortality preclude routine clinical use. SGLT2i should be considered only as individualized investigational therapy under close monitoring pending larger RCTs. PROSPERO (CRD420261303781).
Fibroblast Growth Factor 21 Analogues Improve Fibrosis in Metabolic Dysfunction-Associated Steatohepatitis: An Updated Systematic Review and Meta-Analysis.
Naqash M, Tariq A, Shayan S … +6 more , Sargani SM, Raza MA, Khan NN, Balouch A, Usama RM, Ahmed KAHM
Int J Hepatol · 2026 · PMID 42255485 · Full text
BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) (formerly nonalcoholic steatohepatitis, MASH) is a growing cause of liver morbidity worldwide. Although therapeutic options for MASH fibrosis have expan...
BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) (formerly nonalcoholic steatohepatitis, MASH) is a growing cause of liver morbidity worldwide. Although therapeutic options for MASH fibrosis have expanded, including the approval of resmetirom for noncirrhotic MASH with F2-F3 fibrosis, additional therapies with antifibrotic efficacy remain needed. Fibroblast growth Factor 21 (FGF21) is a liver-derived hormone that regulates lipid metabolism, insulin sensitivity, and energy balance, and long-acting FGF21 analogues have shown promise in Phase 2 trials. We performed a systematic review and meta-analysis to quantify the efficacy and safety of FGF21 analogues in improving liver fibrosis in MASH. METHODS: We searched PubMed, Scopus, and the Cochrane Library (through February 2026) for randomized controlled trials (RCTs) comparing an FGF21 analogue versus placebo in adults with biopsy-confirmed MASH. Primary outcomes were ≥ 1-stage histological fibrosis improvement without MASH worsening. Secondary outcomes included changes in hepatic fat, liver enzymes, and key metabolic parameters. Data were pooled using random-effects models, calculating pooled risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CI). RESULTS: We identified 10 RCTs (total: 1113 patients with F1-F4 fibrosis) meeting inclusion criteria. FGF21 analogue treatment significantly increased the likelihood of achieving ≥ 1-stage fibrosis improvement (RR: 2.25, CI: 1.25-4.03) compared with placebo. FGF21 analogues also produced larger reductions in hepatic fat content, liver stiffness, and fibrosis biomarkers than placebo. The incidence of serious adverse events was similar between groups. The most reported treatment-related side effects were gastrointestinal, especially nausea and diarrhea, and local injection reactions; these were generally mild and did not significantly limit therapy. CONCLUSIONS: FGF21 analogue therapy is associated with significantly greater histological fibrosis improvement in patients with MASH and appears to be well tolerated. These findings suggest that FGF21 analogues may become a valuable pharmacotherapy for MASH, but confirmatory larger trials and long-term data are needed.
LC-Pred: A Transformer-Based Interactive Interface for Liver Cirrhosis Prediction.
Rath B, Dash SR, Mahapatra RK
Int J Hepatol · 2026 · PMID 42183390 · Full text
OBJECTIVES: Incorporating transformer, an innovative deep learning-based model with an authenticated and user-friendly client-server web application namely LC-Pred, this study highlights the early prediction of liver cir...
OBJECTIVES: Incorporating transformer, an innovative deep learning-based model with an authenticated and user-friendly client-server web application namely LC-Pred, this study highlights the early prediction of liver cirrhosis (LC), which will be beneficial for both the clinicians and the LC patients. LC-Pred delivers both single and bulk prediction abilities making it fast, sturdy, and secure to be used in healthcare sectors. METHODS: This study uses a total of 1098 real-time patients' data having both LC and nonliver cirrhosis (NLC) cases to implement and compare traditional scoring systems and AI-based models, by using 20 clinical parameters with two demographic data such as patients' age and gender. RESULTS: The tool consists of authentication, PDF report generation and spontaneous interface elevated for clinical workflow incorporation. Transformer model exhibits the highest accuracy among all the traditional and artificial intelligence (AI) models and is selected to be linked with LC-Pred for classification of cirrhosis. Transformer model accomplishes a vigorous performance with precision recall area under the curve (PR-AUC) of 0.907, receiver operating characteristics area under the curve (ROC-AUC) of 0.989, sensitivity/recall of 0.857 (for LC detection) and specificity of 0.947 (for NLC prediction), Brier score is of 0.027 and test accuracy of 0.977. CONCLUSION: The tool exhibits noteworthy upgradation in AI-assisted hepatology, over traditional scoring techniques like model for end-stage liver disease (MELD) and Child-Pugh, by stabilizing the technical intricacy with clinical efficacy. This note delineates the application framework, model training principles, evaluating results and the importance of implementing an aligned AI system to be utilized by the clinicians.
Comparison of Postoperative MELD-Based Scores in Predicting Mortality After Liver Transplantation: A Retrospective Comparative Study.
Katayama A, Abuelkasem E, Wang DW
Int J Hepatol · 2026 · PMID 42158169 · Full text
BACKGROUND: Postoperative prognostic assessment is critical for patients undergoing liver transplantation (LT). The Model for End-Stage Liver Disease (MELD) scores calculated in the early postoperative period have been s...
BACKGROUND: Postoperative prognostic assessment is critical for patients undergoing liver transplantation (LT). The Model for End-Stage Liver Disease (MELD) scores calculated in the early postoperative period have been shown to be associated with postoperative outcomes. While MELD-Na and MELD 3.0 were developed to improve mortality prediction in pretransplant settings by incorporating serum sodium, albumin, and sex, their comparative utility in the postoperative period remains unclear. METHODS: We conducted a retrospective single-center cohort study including adult LT recipients between January 2012 and June 2023. MELD, MELD-Na, and MELD 3.0 scores were calculated on Postoperative Day (POD) 7. The primary outcome was 30-day all-cause mortality. Predictive performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). Subgroup analyses were performed according to serum sodium, albumin levels, and sex. RESULTS: A total of 1038 patients were included. All three MELD-based scores calculated on POD 7 were associated with 30-day mortality (MELD original, hazard ratio [HR] 1.20, 95% CI 1.13-1.27, < 0.001; MELD-Na, HR 1.20, 95% CI 1.12-1.28, < 0.001; and MELD 3.0, HR 1.21, 95% CI 1.14-1.29, < 0.001, respectively). ROC analysis demonstrated comparable predictive accuracy across MELD, MELD-Na, and MELD 3.0 for 30-day mortality (AUCs: MELD original, 0.82; MELD-Na, 0.79; MELD 3.0, 0.82; overall = 0.24). Exploratory subgroup analyses did not identify any score with consistently superior performance across different strata of sodium, albumin, or sex. CONCLUSION: MELD, MELD-Na, and MELD 3.0 scores calculated on POD 7 showed comparable performance in predicting 30-day mortality after LT. These findings support the use of POD 7 MELD-based scores for postoperative risk stratification, with no meaningful difference in predictive performance among the three scoring systems.
Safety and Drug-Drug Interaction Burden of Direct-Acting Antiviral Therapy for Hepatitis C: A Single-Center Community Hospital Analysis.
Okabe S, Doi A, Matsumoto K … +3 more , Yamamoto M, Fukui K, Nishida T
Int J Hepatol · 2026 · PMID 42089097 · Full text
BACKGROUND: Polypharmacy leads to drug-drug interactions (DDIs) with direct-acting antivirals (DAAs). We quantified the DDI burden (Liverpool categories) and evaluated its association with effectiveness and safety. We as...
BACKGROUND: Polypharmacy leads to drug-drug interactions (DDIs) with direct-acting antivirals (DAAs). We quantified the DDI burden (Liverpool categories) and evaluated its association with effectiveness and safety. We assessed renal function as a predictor of adverse events (AEs) and reported loss to follow-up (LTFU). METHODS: We retrospectively analyzed 145 adults with chronic hepatitis C treated with glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/velpatasvir (SOF/VEL) between February 2018 and October 2024. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12); when SVR12 was missing, SVR24 was substituted (hierarchical SVR). Concomitant drugs were screened using the Liverpool HEP Drug Interaction Checker. The predictors of AEs were assessed using multivariable logistic regression and receiver operating characteristic analysis. A conservative intention-to-treat analysis included missing SVR data as a failure. RESULTS: The median patient age was 67 years, and 23.4% of patients had cirrhosis. Polypharmacy (≥ 5 drugs) occurred in 26.9% of patients, DDIs in 50.3%, multiple DDIs in 14.5%, and contraindicated pairs in 1.4% (all GLE/PIB). AEs occurred in 16.6% of patients, were largely Grades 1-2, and began around Week 2. LTFU was 11.0%. The hierarchical SVR was 99.2%, whereas the conservative analysis was 88.3%. A Cr concentration ≥ 0.86 mg/dL independently predicted AEs (adjusted OR 3.4; 95% CI 1.24-9.2), whereas DDI burden and polypharmacy did not. CONCLUSIONS: Despite frequent DDIs, DDI burden was not independently associated with SVR or AEs. DAA therapy was highly effective and well tolerated. Renal function showed a modest association with AEs.
Changing Landscape of Chronic Liver Diseases in a Tertiary Level Hospital of Bangladesh Over the Last 10 Years.
Shahriar MH, Sarker A, Ghosh T … +4 more , Hoque ME, Arafin MS, Rahman MT, Alam MS
Int J Hepatol · 2026 · PMID 42064707 · Full text
Given significant advances in the treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of chronic liver diseases in Bangladesh may be changing. Our aim was to assess the shi...
Given significant advances in the treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of chronic liver diseases in Bangladesh may be changing. Our aim was to assess the shift in the prevalence of different chronic liver disease etiologies in a tertiary level hospital of Bangladesh over the last 10 years. This was a retrospective observational study conducted in the Department of Hepatology in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. It was based on data from the hospital records (2013-2016 and 2017-2022). A total of 4658 patients were included from the hospital registry between 2013 and 2022. The etiologies of chronic liver disease were compared between two time periods: (2013-2016) and (2017-2022) among these patients. A significant decrease in the prevalence of chronic hepatitis B from 51.1% (2013-2016) to 44.4% (2017-2022) ( < 0.001), chronic hepatitis C from 11.3% (2013-2016) to 10.4% (2017-2022) ( = 0.032), and non-B-non-C from 11.7% (2013-2016) to 8.6% (2017-2022) ( < 0.001) was observed. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD/NASH) increased from 1.2% (2013-2016) to 8.1% (2017-2022) ( < 0.001); anti-HBc (total) from 3.2% (2013-2016) to 5.1% (2017-2022) ( = 0.001), and autoimmune hepatitis (AIH) from 0.2% (2013-2016) to 0.4% (2017-2022) ( = 0.038) also showed a significant increase. Over the last decade (2013-2022), NAFLD has emerged as a rapidly increasing cause of chronic liver disease in Bangladesh, whereas viral etiologies and AIH show a declining trend. Policy makers, clinicians, and stakeholders should take attention to recognize the situation and act properly.
Comparative Efficacy of Bulevirtide, Interferons, and Nucleos(t)ide Analogs for Chronic Hepatitis Delta: A Systematic Review and Network Meta-Analysis.
Karkra R, Mohsen M, Pagán-Busigó JE … +5 more , Shamsian E, Bebawy M, Rella S, Tafesh Z, Gaglio P
Int J Hepatol · 2026 · PMID 42057812 · Full text
BACKGROUND: Chronic hepatitis D virus (HDV) continues to be a global health concern, and the infection remains challenging to treat. Over the past few decades, pegylated interferons, typically in combination with therapy...
BACKGROUND: Chronic hepatitis D virus (HDV) continues to be a global health concern, and the infection remains challenging to treat. Over the past few decades, pegylated interferons, typically in combination with therapy for hepatitis B, have become the standard of care, with considerable side effects and frequently unsatisfactory results. Several new therapies are emerging, including bulevirtide and lonafarnib. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of bulevirtide, interferons, and nucleos(t)ide analogs, alone or in combination, for the treatment of chronic hepatitis D. METHODS: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials and nonrandomized interventional studies assessing HDV RNA suppression, biochemical response, combined response, and histological improvement with various therapies. NMA was performed using a frequentist random-effects model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and forest plots were generated. RESULTS: Thirteen studies ( = 922) were included, studying nine possible treatment arms. At the end of treatment, 31.8% achieved a virological response. Bulevirtide monotherapy (OR 38.63, < 0.05) and combinations with NA (OR 69.36, < 0.05) and peginterferon alpha (OR 260.08, < 0.05) significantly suppressed HDV RNA, with the bulevirtide-peginterferon alpha combination having the highest HDV RNA suppression. At ≥ 24-week follow-up, no regimen maintained significant HDV RNA suppression. Biochemical response was achieved in 42.7% at the end of treatment; however, no group reached statistical significance versus control, though bulevirtide and its combination with peginterferon alpha outperformed peginterferon alpha alone. Combined response was highest with bulevirtide-peginterferon alpha (OR 112.69, < 0.05), followed by bulevirtide monotherapy. Histological response (five studies, = 183) was not statistically significant with any intervention compared with control. CONCLUSION: Bulevirtide and peginterferon alpha combination therapy may offer the most promising treatment for chronic hepatitis D. More studies are needed to assess the efficacy of this regimen and establish the optimum dose and duration of treatment.
Natriuretic Effect of Dapagliflozin in Cirrhosis With Ascites: A Randomized, Placebo-Controlled Crossover Trial.
Kongphakdee N, Piewchan S, Sanpawithayakul K … +2 more , Chonprasertsuk S, Siramolpiwat S
Int J Hepatol · 2026 · PMID 41958639 · Full text
BACKGROUND: Ascites is a frequent complication of decompensated liver cirrhosis and is associated with a poor prognosis. Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, induces osmotic diuresis and nat...
BACKGROUND: Ascites is a frequent complication of decompensated liver cirrhosis and is associated with a poor prognosis. Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, induces osmotic diuresis and natriuresis, with established use in heart failure. However, studies on SGLT2 inhibitors in cirrhotic patients with ascites are limited. OBJECTIVES: The objective of this study is to evaluate changes in urine parameters in cirrhotic patients with ascites treated with dapagliflozin. METHODS: This randomized, double-blind, placebo-controlled, crossover trial enrolled 10 patients with Child-Pugh Class B or C cirrhosis who had persistently moderate or tense ascites. Participants received dapagliflozin or placebo for 4 weeks, followed by a 2-week washout, and then crossed over to alternate treatment. The primary outcome was the change in 24-h urine sodium (UNa) excretion on Days 0, 3, and 28. Secondary outcomes included changes in 24-h urine volume (UV) and serum sodium. RESULTS: Dapagliflozin significantly increased 24-h urinary sodium excretion at Day 3 compared with placebo (treatment difference +35.1 mmol/day; 95% CI 17.5-52.7; < 0.001), indicating a transient natriuretic effect. This effect was not sustained at Day 28 ( = 0.42). There were no significant changes in 24-h UV or serum sodium at either time point. At the end of the dapagliflozin phase, 5 of 7 evaluable participants demonstrated improvement in ascites grade, whereas 2 did not. One serious adverse event occurred; one participant died during the washout period after completing the placebo phase due to variceal bleeding complicated by spontaneous bacterial peritonitis. CONCLUSIONS: In cirrhotic patients with persistent ascites, dapagliflozin was associated with a transient increase in 24-h urinary sodium excretion, without significant sustained effects on urine volume or serum sodium. Dapagliflozin was generally well tolerated in this small pilot trial. TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20241016007.
Association Between Liver Enzymes and Metabolic Syndrome: A Population-Based Cross-Sectional Study of the Bandar Kong Cohort Study.
Ghazalgoo A, Kheirandish M, Hashemi SM … +5 more , Salarpour E, Basham A, Saberian P, Amini-Salehi E, Safa H
Int J Hepatol · 2026 · PMID 41958638 · Full text
BACKGROUND: Metabolic syndrome (MetS) is a major global health concern that increases morbidity and mortality from cardiometabolic diseases. We refined the rationale to highlight the mechanistic involvement of the liver...
BACKGROUND: Metabolic syndrome (MetS) is a major global health concern that increases morbidity and mortality from cardiometabolic diseases. We refined the rationale to highlight the mechanistic involvement of the liver in metabolic dysregulation. METHODS: This population-based study was conducted on 3896 adults aged between 35 and 70 (57.2% female) who participated in the Bandare-Kong Non-Communicable Diseases (BKNCD) cohort study. Participants were categorized into normal quartiles and abnormal levels of liver enzymes including gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). MetS was defined based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for Iranian population. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and values, adjusting for age, sex, residence, BMI, physical activity, energy intake, and financial status. RESULTS: The prevalence of MetS was 36.6%. After multivariable adjustment, abnormal levels of GGT (OR = 1.91, 95% CI: 1.61-2.28, < 0.001), ALT (OR = 1.60, 95% CI: 1.34-1.90, < 0.001), ALP (OR = 1.48, 95% CI: 1.07-2.03, = 0.01), and AST (OR = 1.39, 95% CI: 1.09-1.77, = 0.007) were significantly associated with higher odds of MetS. Within normal ranges, the highest quartile of GGT (OR = 2.81, 95% CI: 2.22-3.56, < 0.001), ALT (OR = 2.39, 95% CI: 1.89-3.03, < 0.001), and ALP (OR = 1.63, 95% CI: 1.30-2.04, < 0.001) showed significant associations, while AST did not. CONCLUSION: Serum liver enzyme levels, including those within normal range, were strongly associated with MetS. GGT showed relatively stronger associations compared with other enzymes; however, these findings should not be interpreted as diagnostic superiority because no performance metrics (AUC, PPV, and NPV) were evaluated. ALT and ALP also showed meaningful associations. Future studies should assess diagnostic accuracy before considering clinical implementation.
Machine Learning Models to Predict Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) With Simple Anthropometric and Biochemical Variables: A Cross-Sectional Study in US Population.
Du S, Yu H, Du J … +1 more , Xu Y
Int J Hepatol · 2026 · PMID 41930207 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern. This study was aimed at exploring the feasibility of utilizing machine learning (ML) algorithms to predic...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern. This study was aimed at exploring the feasibility of utilizing machine learning (ML) algorithms to predict MASLD in large general populations based on simple anthropometric and biochemical parameters. METHODS: Data from the 2017-2020 cycles of the US National Health and Nutrition Examination Survey (NHANES) were utilized. A total of 6814 participants (53.0% female) with complete transient elastography data were included. MASLD was defined as a controlled attenuation parameter ≥ 280 dB/m, with cardiometabolic risk factor and without excessive alcohol use. Key characteristics and biomarkers associated with MASLD were identified using the least absolute shrinkage and selection operator (LASSO) and the Boruta algorithms. ML methods, including logistic regression (LR), extreme gradient boosting (XGBoost), bootstrap aggregating, random forest, naive Bayes, light gradient boosting machine (LightGBM), decision tree, and support vector machines, were employed to develop the MASLD prediction models. RESULTS: The median age of the 6814 participants was 53 years (interquartile range: 37~65). MASLD was detected among 2611 (38.3%) participants. Key predictors selected via LASSO and Boruta algorithms included body weight, standing height, waist circumference, diagnosis of diabetes, alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase. The areas under the receiver operating characteristic curves of LR, XGBoost, and other ML models were 0.841, 0.837, 0.815, 0.838, 0.814, 0.842, 0.796, and 0.828 in the internal validation cohort. Results indicate that LR, XGBoost, and LightGBM models outperform other models in predicting MASLD. CONCLUSIONS: The ML models of LR, XGBoost, and LightGBM are effective and simplified tools for predicting MASLD in the US general population. This study underscores the potential of ML models with simple noninvasive biomarkers in enhancing early detection and personalized management of fatty liver disease.
Injecting Drug Use History and Younger Age Worsen Adherence to Scheduled Hospital Visits in Glecaprevir and Pibrentasvir Therapy for Chronic Hepatitis C.
Tawara S, Watanabe A, Yamaguchi J … +8 more , Omi M, Miyazaki T, Taguchi H, Kiyota R, Yamai T, Kawai S, Inoue T, Yakushijin T
Int J Hepatol · 2026 · PMID 41573355 · Full text
AIM: The use of direct-acting antivirals (DAAs) against the Hepatitis C virus (HCV) has rapidly expanded since their introduction. However, some patients with HCV infection may still not receive appropriate medical care....
AIM: The use of direct-acting antivirals (DAAs) against the Hepatitis C virus (HCV) has rapidly expanded since their introduction. However, some patients with HCV infection may still not receive appropriate medical care. This study analyzed the characteristics and adherence of the population receiving therapy with two later-generation DAAs, glecaprevir (GLE) and pibrentasvir (PIB), to investigate the clinical challenges associated with HCV treatment. METHODS: A total of 141 consecutive patients who underwent GLE/PIB therapy for chronic HCV infection between December 2017 and June 2021 were enrolled. Patient backgrounds and adherence were retrospectively analyzed. RESULTS: Median patient age was 61 years. Eighteen patients had a history of injecting drug use (IDU), accounting for 13% of the sample. At the end of treatment, three patients (2.1%) self-discontinued hospital visits. The number of patients who self-discontinued hospital visits gradually increased over time to 9 (6.4%) at 4 weeks after treatment, 16 (11.3%) at 12 weeks after treatment, and 24 (17.0%) at 24 weeks after treatment. The sustained viral response rate after 12 weeks, excluding patients who self-discontinued hospital visits, was 96.8% (121/125). In a multivariate analysis, age < 60 years and a history of IDU were significant factors associated with the self-discontinuation of hospital visits. The hazard ratio (HR) for those younger than 60 years old was 3.17 ( = 0.012), whereas the HR for those with a history of IDU was 2.41 ( = 0.036). CONCLUSIONS: History of IDU and younger age were significantly associated with poor adherence to GLE/PIB treatment.
Global Bivariate Meta-Analysis of FIB-4 Cut-Offs to Rule Out Advanced Fibrosis in MASLD.
Ghosal A, Ghosal S
Int J Hepatol · 2026 · PMID 41540983 · Full text
BACKGROUND: The fibrosis-4 (FIB-4) index, a non-invasive marker, evaluates advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), but the variability in its performance across different po...
BACKGROUND: The fibrosis-4 (FIB-4) index, a non-invasive marker, evaluates advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), but the variability in its performance across different populations remains unclear. METHODS: We conducted a systematic review and bivariate meta-analysis of 14 studies ( = 5521) with 2 × 2 contingency data for FIB-4 at thresholds < 1.0 and < 1.3, compared with liver biopsy or transient elastography (TE). The Reitsma model (R v4.4.3) estimated pooled sensitivity and specificity. Subgroup analyses assessed region (India vs. global) and reference standard effects, with heterogeneity and publication bias (Deeks' test) evaluated. RESULTS: Pooled sensitivity was 0.73 (95% CI: 0.69-0.77), and specificity was 0.69 (95% CI: 0.61-0.76) at < 1.3. The < 1.0 threshold demonstrated higher specificity (0.83, 95% CI: 0.75-0.89) but lower sensitivity (0.63, 95% CI: 0.58-0.68). Indian cohorts ( = 3) exhibited higher specificity (0.83) than the global estimate (0.66) at < 1.3, whereas sensitivity remained similar. CONCLUSION: FIB-4 below 1.3 is a useful initial tool for ruling out advanced fibrosis in MASLD, with potential regional variations in specificity. Larger studies are needed to confirm cut-offs, supporting tailored guidelines with sequential testing.
Noninvasive Assessment of Prehepatic Portal Hypertension: Pilot Data on Spleen Stiffness in Portal Vein Thrombosis.
Chan KTL, Chan OL, Lam YY … +1 more , Lai SWL
Int J Hepatol · 2025 · PMID 41476788 · Full text
BACKGROUND: Portal vein thrombosis (PVT) is a vascular liver disorder defined by a thrombus in the portal vein or its intrahepatic branches. Computed tomography (CT) and upper endoscopy are, respectively, used to monitor...
BACKGROUND: Portal vein thrombosis (PVT) is a vascular liver disorder defined by a thrombus in the portal vein or its intrahepatic branches. Computed tomography (CT) and upper endoscopy are, respectively, used to monitor for PVT progression and portal hypertensive complications. A noninvasive modality-spleen stiffness (SS)-has shown promise in identifying clinically significant portal hypertension (CSPH) in cirrhosis. It is unknown whether SS demonstrates any correlation with PVT, a condition associated with prehepatic portal hypertension. AIMS: The primary aim was to determine the association between SS and the presence of PVT. The secondary aim was to evaluate the association between SS and portal hypertension-related complications among patients with PVT. METHODS: This cross-sectional study was undertaken at two regional hospitals in Hong Kong from January 2023 to March 2024. Patients were identified via CT and allocated to either the PVT or non-PVT group. Chronic liver disease was an exclusion criterion for both groups. SS was assessed using transient elastography within 3 months of PVT diagnosis. Demographic, clinical, and laboratory data were collected within 3 months of PVT diagnosis. RESULTS: A total of 46 patients with PVT (median age, 69 years; interquartile range [IQR], 62-78; 74% male) were compared with 45 controls. Both SS and liver stiffness (LS) were significantly higher in the PVT cohort than in controls (SS: 27.9 [IQR, 19.5-42.8] vs. 16.9 kPa [IQR, 13.6-21.2], < 0.001; LS: 6.0 [IQR, 4.8-8.6] vs. 4.6 kPa [IQR, 3.7-5.9], < 0.001). Among patients with PVT, those with portal hypertension-related complications demonstrated markedly elevated SS compared with those without complications (77.7 [IQR, 47.2-85.0] vs. 24.4 kPa [IQR, 18.9-37.1], < 0.001). Furthermore, SS values increased in proportion to the anatomical extent of PVT involvement. CONCLUSION: Elevated SS was observed in patients with PVT, particularly in those with PVT-induced portal hypertension. Large-scale, prospective studies are warranted to confirm the association between SS and PVT and to establish its potential role in noncirrhotic portal hypertension.
PFKL Inhibition by DT-13: A Novel Approach to Combat Hepatocellular Carcinoma.
Yu Q, Hu L, Tan C … +2 more , Gao M, Wen Z
Int J Hepatol · 2025 · PMID 41476787 · Full text
Aerobic glycolysis modulates proliferation, apoptosis, immune evasion, and targeted drug resistance in hepatocellular carcinoma (HCC) patients. Therefore, inhibiting aerobic glycolysis could represent a novel chemotherap...
Aerobic glycolysis modulates proliferation, apoptosis, immune evasion, and targeted drug resistance in hepatocellular carcinoma (HCC) patients. Therefore, inhibiting aerobic glycolysis could represent a novel chemotherapeutic strategy for HCC. The effects of Baily's Saponin C (DT-13), a novel compound isolated from the traditional Chinese medicine (Decne) Baily, on HCC and its underlying mechanism remain unknown. This study revealed that DT-13 induces apoptosis and inhibits the in vivo and in vitro proliferation of HCC cells. Furthermore, DT-13 significantly reduced glucose consumption and lactate production. Moreover, it was observed that DT-13 could inhibit Phosphofructokinase-1 liver (PFKL) type via c-myc signaling to modulate the aerobic glycolysis, proliferation, and apoptosis of HCC. Moreover, DT-13 improved the anticancer effects of sorafenib in HCC. In summary, this study provided evidence for the potential application of DT-13 in HCC treatment.
Randomized Controlled Trial Evidence on Peroxisome Proliferator-Activated Receptor (PPAR) Agonists in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.
Dar MS, Fatima T, Azhar SD … +13 more , Rehman Z, Affan M, Saleem YM, Ali S, Athar F, Ishaq S, Ain NU, Zahid J, Khan AW, Ovais H, Ahmad TKF, Ahmed KAHM, Bharadwaj HR
Int J Hepatol · 2025 · PMID 41377195 · Full text
PURPOSE: Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid (UDCA) is the first-line treatment, while obeticholic...
PURPOSE: Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid (UDCA) is the first-line treatment, while obeticholic acid (OCA) serves as a second-line option because of moderate UDCA nonresponsiveness and cirrhosis-related concerns. Additional therapies are necessary because of recent warnings regarding OCA usage in patients with cirrhosis. This study aimed to evaluate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in PBC. METHODS: We searched PubMed, Google Scholar, and the Cochrane Library until October 2023. We included all randomized controlled trials (RCTs) that studied the efficacy and safety of PPAR agonists in treating PBC. The primary outcome of interest was change in alkaline phosphatase (ALP) levels. In contrast, the secondary outcomes were changes in gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), triglyceride levels, and pruritis. We used a random-effects model to calculate the risk ratio (RR) and standardized mean difference (SMD) with 95% CI. RESULTS: A total of eight RCTs ( = 515) were eligible for the analysis. Pooled data showed beneficial effects of PPAR agonists compared with placebo for change in ALP level (SMD = -2.81, 95%CI = -4.10 to - 1.51; < 0.0001, I = 96%), GGT level (SMD = -1.29, 95%CI = -2.09 to - 0.48; = 0.002, I = 92%), TBil level (SMD = -0.77, 95%CI = -1.32 to - 0.22; = 0.006, I = 86%), and Tg level (SMD = -0.99, 95%CI = -1.63 to - 0.35; = 0.003, I = 83%). There was no significant difference between PPAR agonists and placebo for ALT level (SMD = -0.93, 95%CI = -1.94 to 0.08; = 0.07, I = 95%), AST level (SMD = -0.01, 95%CI = -0.67 to 0.66; = 0.99, I = 91%), and pruritus (RR = 0.77, 95%CI = 0.29 to 2.06; = 0.60, I = 34%). CONCLUSION: Our study found a superior efficacy of PPAR agonists compared with placebo for change in ALP, GGT, TBil, and Tg levels, highlighting the potentially beneficial effect of PPAR agonists on liver health.
Association Between Subclinical Hypothyroidism and MASLD: A Systematic Review and Meta-Analysis.
Amdetsion GY, Pan CW, Tebeje H … +3 more , Sapkota A, Nandyal S, Kotwal V
Int J Hepatol · 2025 · PMID 41357781 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder that can progress to cirrhosis and hepatocellular carcinoma. Although overt hypothyroidism has bee...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder that can progress to cirrhosis and hepatocellular carcinoma. Although overt hypothyroidism has been identified as a MASLD risk factor, the impact of subclinical hypothyroidism (SCH), which affects approximately 4.6% of US adults, remains unclear. We conducted a systematic review and meta-analysis to determine whether SCH is independently associated with MASLD and to inform targeted screening recommendations. METHODS: We systematically searched PubMed, Embase, Cochrane, ClinicalTrials.gov, and Web of Science up to June 2025 for studies evaluating the association between SCH and MASLD. Random-effects meta-analyses were performed on eligible cross-sectional and longitudinal studies. RESULTS: We screened 537 records and ultimately included 10 high-quality studies with 71,332 participants. Overall, 22.3% had MASLD and 7.7% had SCH. In cross-sectional analyses ( = 39,814), SCH was linked to 46% higher odds of MASLD (pooled OR = 1.46, 95% CI 1.23-1.73; = 36%). Across four longitudinal cohorts ( = 31,518), SCH raised the risk of incident MASLD by 59% (pooled HR = 1.59, 95% CI 1.05-2.40). Limiting the analysis to prospective studies strengthened the association (HR = 1.90, 95% CI 1.50-2.39) and eliminated heterogeneity ( = 0). CONCLUSIONS: This meta-analysis provides evidence that SCH is associated with both higher odds of prevalent MASLD and increased risk of incident MASLD. Clinicians should consider routine screening for MASLD in patients with SCH and vice versa.
Impact of Elevated Liver Enzymes on the Severity of Clinical Course of COVID-19: A Retrospective Study From Saudi Arabia.
Makkawy E, Alamro SM, Ibn Awadh S … +4 more , Basalasil R, Alkhelaiwi Z, Al-Mutairi B, Rebh F
Int J Hepatol · 2025 · PMID 41346355 · Full text
BACKGROUND: According to recent research, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause liver injury, which may be linked to a poorer prognosis. In this retrospective study, we evaluated the inci...
BACKGROUND: According to recent research, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause liver injury, which may be linked to a poorer prognosis. In this retrospective study, we evaluated the incidence of high liver enzyme levels in patients with COVID-19 and their correlation with the severity and prognosis of clinical outcomes. METHODS: A retrospective cohort study was performed from March 2020 to October 2020 at Prince Mohammed Bin Abdulaziz Hospital (PMAH), Riyadh, Saudi Arabia. Demographic information of COVID-19 patients as well as data on clinical features and laboratory parameters were collected. Pearson's correlation () test was used to assess the correlation between elevated liver enzymes and COVID-19 severity. The multivariate logistic binary regression analysis was used to identify the predictors of elevated liver enzyme levels and mortality among patients with COVID-19. RESULTS: This cohort included 1033 patients, 73% of whom were male, with a mean age of 49.9 years. Elevated liver enzymes were observed in 52.7% of patients, most commonly with a hepatitis pattern (63.1%). Elevated levels of hemoglobin, creatine kinase-myocardial band, and C-reactive protein, as well as pneumoniae, the requirement of an intensive care unit, comorbidities, and the use of paracetamol, -lactamase, and steroids were significant predictors of elevated liver enzymes ( < 0.05). Interestingly, Saudi patients ( = 0.019) were found to be a significant protective predictor of elevated liver enzymes. Our findings revealed that elevated liver enzyme levels were significantly correlated with the severity of COVID-19 ( < 0.05) in terms of qSOFA score. Moreover, older age, diabetes, qSOFA score, and elevated hepatitis enzymes were associated with mortality ( = 0.043). CONCLUSIONS: Elevated liver enzyme levels were common in patients with COVID-19 and were associated with the severity and prognosis of clinical outcomes.
Impact of Age on Mortality and Decompensation Events in Patients With Liver Cirrhosis: A Multicenter, Propensity Score Matched Study.
Shabbir M, Salazar M, Kayali Z
Int J Hepatol · 2025 · PMID 41333005 · Full text
BACKGROUND: The incidence of cirrhosis is increasing in the older population. Limited data are available on the disease progression and mortality in the older population with cirrhosis. This study is aimed at evaluating...
BACKGROUND: The incidence of cirrhosis is increasing in the older population. Limited data are available on the disease progression and mortality in the older population with cirrhosis. This study is aimed at evaluating the impact of age at diagnosis on all-cause mortality and decompensation events in patients with liver cirrhosis. METHODS: This is a retrospective cohort study utilizing TriNetX. ICD codes were used to identify individuals with the diagnosis of liver cirrhosis between the ages of 20 and 80. Patients with the diagnosis of congestive heart failure (CHF), end-stage renal disease (ESRD), chronic kidney disease (CKD) Stage IV and V, human immunodeficiency virus (HIV), malignant neoplasm, and psychoactive substance abuse were excluded from the analyses. Patients were divided into two cohorts: Cohort 1 included individuals with the diagnosis of liver cirrhosis between the ages of 51 and 80, and Cohort 2 included individuals with the diagnosis between the ages of 20 and 50. Statistical analyses were conducted using TriNetX Live. A 1:1 propensity score matching was performed for variables including race, gender, ethnicity, comorbidities, laboratory values for MELD 3.0, and etiology of liver cirrhosis. There were 70,983 patients in each cohort after matching. The primary outcome was all-cause mortality, and the composite outcome of decompensation events at 5- and 10-year intervals from the age of diagnosis of liver cirrhosis. Secondary outcomes included the risk of decompensation events, all-cause hospitalization at 5-year intervals, and a subgroup analysis of all-cause mortality and decompensation events among males and females. RESULTS: Older age at diagnosis of liver cirrhosis was associated with increased all-cause mortality at 5 years (aOR 1.378, 95% CI: 1.335-1.422; < 0.001) and 10 years (aOR 1.418, 95% CI: 1.376-1.462; < 0.001). These patients also demonstrated an increased risk of decompensation events at 5 years (aOR 1.236, 95% CI: 1.199, 1.275; < 0.001) and at a 10-year interval (aOR 1.266, 95% CI: 1.229, 1.305; < 0.001). At 5-year intervals, these patients (Cohort 1) were found to have an increased risk of variceal bleeding (aOR 1.309, 95% CI: 1.258-1.361; < 0.001), ascites (aOR 1.114, 95% CI: 1.052-1.180; < 0.001), hepatic encephalopathy (aOR 1.1, 95% CI: 1.026-1.180; < 0.001), hepatopulmonary syndrome (aOR 1.45, 95% CI: 0.820-2.564; = 0.101), and hepatocellular carcinoma (aOR 2.924, 95% CI: 2.477-3.453, < 0.001). Conversely, in younger patients, there were increased odds of developing spontaneous bacterial peritonitis (SBP) (aOR 0.848, 95% CI: 0.720-0.998, = 0.02) and hepatorenal syndrome (HRS) (aOR 0.753, 95% CI: 0.651-0.871, < 0.01). The differences were persistent in a subgroup analysis among males (mortality, aOR 1.37, 95% CI: 1.319, 1.424; < 0.001) and females (mortality aOR 1.384, 95% CI: 1.311, 1.462; < 0.001). CONCLUSION: Older age at diagnosis of liver cirrhosis is associated with increased all-cause mortality and key decompensation events. Certain conditions, like SBP and HRS, are more common in the younger population, likely due to increased alcohol abuse. Early detection of portal hypertension and early appropriate prophylaxis for variceal bleeding can provide benefit in this high-risk population, although the exact impact of such strategies needs further studies. Besides early recognition, alcohol remains a key factor that needs to be concomitantly addressed as it drives life-threatening decompensating events.
Unraveling the Role of CYP2E1 in Antitubercular Drug-Induced Hepatotoxicity: From Molecular Mechanisms to Clinical Implications.
Bishnu D, Santra S, Purkait S … +1 more , Santra A
Int J Hepatol · 2025 · PMID 41323558 · Full text
Antitubercular (AT) drugs, particularly isoniazid (INH), rifampicin (RIF), pyrazinamide (PYZ), and ethambutol (EMB), are the cornerstone of tuberculosis (TB) treatment. However, their use is often limited by the risk of...
Antitubercular (AT) drugs, particularly isoniazid (INH), rifampicin (RIF), pyrazinamide (PYZ), and ethambutol (EMB), are the cornerstone of tuberculosis (TB) treatment. However, their use is often limited by the risk of hepatotoxicity, a potentially severe side effect. Among the factors implicated in drug-induced liver injury, cytochrome P450 2E1 (CYP2E1) is emerging as a key enzyme in the pathogenesis of hepatotoxicity. CYP2E1 is involved in the oxidative metabolism of many xenobiotics, including AT drugs, and is known to produce reactive oxygen species (ROS) during the metabolism process, which can lead to cellular damage. This review investigates the potential role of CYP2E1 in the mechanisms behind AT drug-induced hepatotoxicity and explores the biochemical and molecular pathways through which CYP2E1 might contribute to liver injury. Genetic polymorphisms in the CYP2E1 gene, which affect its activity, may also play a role in individual susceptibility to AT drug-induced hepatotoxicity. This review also deals with how multifactorial interactions including genetic polymorphisms in CYP2E1, N-acetyl transferase 2 (NAT2), and glutathione-S-transferase (GST), as well as factors such as drug-drug interactions, nutritional status, coexisting infections (e.g., hepatitis B/C), and alcohol consumption collectively modulate individual susceptibility to AT drug-induced hepatotoxicity. By elucidating the role of CYP2E1 in AT drug-induced hepatotoxicity, this review provides a foundation for future therapeutic strategies, including the development of safer drug formulations or adjunct therapies targeting CYP2E1 to mitigate hepatotoxicity.
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