Journal of Clinical and Experimental Hepatology最新文献

{"title":"Living Donor Liver Transplantation for Pediatric Wilson’s Disease-related Acute Liver Failure—Hard Work With High Rewards","authors":"Somashekara H. Ramakrishna ,&nbsp;Vellaichamy Katheresan ,&nbsp;Mohan B. Kasala ,&nbsp;Karnan Perumal ,&nbsp;Selvakumar Malleeswaran ,&nbsp;Joy Varghese ,&nbsp;Rajanikanth V. Patcha ,&nbsp;Prashant Bachina ,&nbsp;Poushya S. Madhavapeddy ,&nbsp;Mettu S. Reddy","doi":"10.1016/j.jceh.2025.102560","DOIUrl":"10.1016/j.jceh.2025.102560","url":null,"abstract":"<div><h3>Background</h3><div>Liver transplantation (LT) is indicated for children with Wilson’s disease (WD) presenting with acute liver failure (ALF) or with chronic liver disease (CLD) that has progressed to decompensation. We present our experience of living donor liver transplantation (LDLT) for pediatric WD, discuss the challenges of managing WD-ALF and compare outcomes of children presenting with WD-ALF with WD-CLD.</div></div><div><h3>Methods</h3><div>We compared presentation and outcomes of the WD-ALF and WD-CLD cohorts. Fifty-three children (WD-ALF: 28 (53%), WD-CLD: 25 (47%)) underwent LDLT for WD.</div></div><div><h3>Results</h3><div>WD-ALF group had higher Kings New Wilson Index (KNWI) (15 vs 9, <em>P</em> = 0.001), higher pediatric end-stage liver disease/model for end-stage liver disease score (35 vs 20, <em>P</em> = 0.001), were more frequently encephalopathic (64% vs 4%, <em>P</em> = 0.001), and had ongoing hemolysis (86% vs 28%, &lt;0.001). Preoperative mechanical ventilation, operative continuous renal replacement therapy (CRRT), therapeutic plasma exchange (TPE) was needed in 32%, 46.5%, and 89% of WD-ALF children, respectively. WD-ALF patients had longer postoperative ICU stay (4.5 days vs 3 days, <em>P</em> = 0.001), longer hospital stay (20.5 days vs 14 days, <em>P</em> = 0.001), more major complications (57% vs 20%, <em>P</em> = 0.006). WD-ALF cohort also had more postoperative neurological complications (42.9% vs 8%, <em>P</em> = 0.004) and invasive fungal infections (21.4% vs none, <em>P</em> = 0.024). There were two perioperative (90 day) mortalities in WD-ALF group and none in WD-CLD group. Patient survival of the entire cohort at median follow-up of 26 months was 94.3% and all survivors had good allograft function neurological sequelae. Patient survival was inferior for WD-ALF cohort though the difference was not statistically significant (88.5% vs 100%, log rank test, <em>P</em> = 0.089).</div></div><div><h3>Conclusion</h3><div>LDLT is a curative treatment for children with WD with excellent short-term and long-term outcomes. WD-ALF patients can have a complicated postoperative course but have good long-term survival.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102560"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac Evaluation in Liver Transplant Candidates","authors":"Dinesh Jothimani,&nbsp;Navin Kumar Marannan,&nbsp;Karan Jain,&nbsp;Aswin Krishna,&nbsp;Mohamed Rela","doi":"10.1016/j.jceh.2025.102554","DOIUrl":"10.1016/j.jceh.2025.102554","url":null,"abstract":"<div><div>Liver transplantation (LT) is the only cure for patients with end-stage liver disease. With an increase in the prevalence of obesity and associated metabolic risk factors cardiovascular disease, in particular coronary artery disease is increasingly recognised in patients with liver cirrhosis. Identification and management of these cardiovascular risk factors may influence post-transplant clinical outcomes. A detailed assessment of patients’ cardiovascular status is therefore crucial in the decision-making of patients for LT. Identification of patients with CAD requires risk stratification around perioperative and long term post-operative period. Advanced age, male sex, smoking diabetes mellitus, hypertension, obesity and metabolic-associated steatohepatitis (MASH) cirrhosis significantly increase the risk of coronary artery disease (CAD).</div><div>Patients with these high-risk factors should undergo cardiac investigations with higher sensitivity to identify CAD. Patients with low-risk factors for CAD may undergo cardiac investigations with high specificity. Patients with cirrhosis may also suffer from conditions directly related to liver disease such as cirrhotic cardiomyopathy and porto-pulmonary hypertension, and conditions unrelated to liver disease such as arrhythmias. Rarely, valvular heart disease may be identified during transplant evaluation. Clinicians managing patients for liver transplantation should carefully evaluate cardiovascular risk and treat it appropriately prior to the surgery, to minimise post-transplant complication. A multidisciplinary approach involving transplant physicians, anaesthetists, cardiologists and transplant surgeons is strongly recommended.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102554"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Understanding of Liver Fibrosis in Type 2 Diabetes: Methodological Considerations and Future Directions","authors":"Mohamed El-Kassas,&nbsp;Khalid M. AlNaamani,&nbsp;Yusuf Yilmaz,&nbsp;Khalid A. Alswat","doi":"10.1016/j.jceh.2025.102553","DOIUrl":"10.1016/j.jceh.2025.102553","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102553"},"PeriodicalIF":3.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Accuracy of Noninvasive Scores for Fibrotic MASH in a Cohort of Biopsy-proven MASLD Patients With Predominantly High BMI in the Primary Care Setting","authors":"Alexa Giammarino ,&nbsp;Nairuti Shah ,&nbsp;Maham Ghani ,&nbsp;Hassam Ali ,&nbsp;Sanjaya K. Satapathy","doi":"10.1016/j.jceh.2025.102556","DOIUrl":"10.1016/j.jceh.2025.102556","url":null,"abstract":"<div><h3>Background</h3><div>Currently, the Fibrosis-4 (FIB-4) and nonalcoholic fatty liver disease fibrosis score (NFS) are used to predict fibrosis and steatosis in patients with or at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). More recently, the fibrotic nonalcoholic steatohepatitis (NASH) index (FNI) and steatosis-associated fibrosis estimator (SAFE) have been created. We have compared the accuracy of these noninvasive scoring systems in MASLD patients.</div></div><div><h3>Methods</h3><div>This is a retrospective analysis of 244 biopsy-proven MASLD patients from a tertiary health care system. Score performances were determined by calculating the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).</div></div><div><h3>Results</h3><div>About 25 (10.3%) patients had fibrotic metabolic dysfunction-associated steatohepatitis (MASH). The FNI score was best at predicting fibrotic MASH with an AUROC of 0.78, while NFS was the worst at predicting fibrotic NASH with an AUROC of 0.60. In the entire cohort, FNI of 0.33, FIB-4 of 2.67, SAFE &gt;100, and NFS &gt;0.675 had PPVs of 17%, 31%, 17%, and 16%, respectively, and NPVs of 97%, 92%, 96%, and 91%, respectively. Specificity was greatest for FIB4 at 92% and NFS at 86%, whereas the sensitivity was greatest for FNI and SAFE scores at 88% and 80%, respectively.</div></div><div><h3>Conclusion</h3><div>FNI and SAFE scores have superior diagnostic accuracy for fibrotic MASH compared to other scoring systems. While liver biopsy remains the gold standard diagnostic method, noninvasive scores like FNI, and SAFE scores can be used in everyday clinical practice to assess for fibrotic MASH.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102556"},"PeriodicalIF":3.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Impact of Therapeutic Plasma Exchange on Organ Function in Patients With ACLF: A Retrospective, Single-center Propensity Score-matched Cohort Study","authors":"Jonas Schumacher ,&nbsp;Reinhard Henschler ,&nbsp;Raymund Buhmann ,&nbsp;Sirak Petros ,&nbsp;Lorenz Weidhase ,&nbsp;Rhea Veelken ,&nbsp;Adam Herber ,&nbsp;Janett Fischer ,&nbsp;Thomas Berg","doi":"10.1016/j.jceh.2025.102550","DOIUrl":"10.1016/j.jceh.2025.102550","url":null,"abstract":"<div><h3>Background and aims</h3><div>Acute on chronic liver failure (ACLF) represents the most severe outcome of acute decompensation in patients with liver cirrhosis, with ACLF-grade 3 carrying a nearly 80% mortality rate within 28 days. Prognosis is especially dire within the first 3–7 days with full organ support. Currently, effective treatments are limited to transplantation, but therapeutic plasma exchange (TPE) may contribute by removing harmful inflammatory mediators and replenishing essential proteins, thus offering promise for patients unresponsive to standard medical treatments (SMT).</div></div><div><h3>Material and methods</h3><div>This retrospective study analyzed patients with ACLF receiving SMT with or without TPE at a tertiary care transplant center. Patients were monitored for at least 90 days postdiagnosis. The primary endpoint was 28-day transplant-free survival, with secondary endpoints including 90-day transplant-free survival, organ dysfunction parameters, and chronic liver failure consortium (CLIF-C) scores. A cohort of 25 patients treated with SMT + TPE and 65 with SMT alone was identified. Propensity scores enabled 1:1 matching, resulting in a final analysis of 40 patients (20 TPE group and 20 SMT group).</div></div><div><h3>Results</h3><div>Patients underwent a median of three (IQR 2.25–5) TPE sessions, starting a median of 14 (IQR 7.25–17) days after ACLF diagnosis. Significant improvements were observed in ACLF grade, CLIF-C-ACLF score, hepatic encephalopathy and prothrombin time 24–48 h postfinal TPE session. The 28-day transplant-free survival rates were 70% in the TPE group versus 45% in the SMT group (<em>P</em> = 0.083) and at 90 days, survival rates were 30% in bothgroups (<em>P</em> = 0.426). Patients unresponsive to SMT who received TPE had significantly higher 28-day transplant-free survival rates compared to those treated with SMT alone (70.6% vs 26.7%, <em>P</em> = 0.008).</div></div><div><h3>Conclusion</h3><div>TPE may demonstrate potential efficacy in ameliorating organ dysfunction in patients with ACLF and could contribute to enhanced short-term survival in selected cases. However, clear criteria for initiating TPE have yet to be established. Unresponsiveness to standard medical treatment may serve as a potential surrogate parameter to guide clinical decision-making on an individual basis.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102550"},"PeriodicalIF":3.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics Analysis and Machine Learning-based Identification of Molecular Signatures for Diagnostic Classification in Liver Disease Types Along the Microbiota-gut-liver Axis","authors":"Betul Comertpay,&nbsp;Esra Gov","doi":"10.1016/j.jceh.2025.102552","DOIUrl":"10.1016/j.jceh.2025.102552","url":null,"abstract":"<div><h3>Background</h3><div>Liver disease, responsible for around two million deaths annually, remains a pressing global health challenge. Microbial interactions within the microbiota–gut–liver axis play a substantial role in the pathogenesis of various liver conditions, including early chronic liver disease (eCLD), chronic liver disease (CLD), acute liver failure (ALF), acute-on-chronic liver failure (ACLF), non-alcoholic fatty liver disease (NAFLD), steatohepatitis, and cirrhosis. This study aimed to identify key molecular signatures involved in liver disease progression by analyzing transcriptomic and gut microbiome data, and to evaluate their diagnostic utility using machine learning models.</div></div><div><h3>Methods</h3><div>Transcriptomic analysis identified differentially expressed genes (DEGs) that, when integrated with regulatory elements microRNAs, transcription factors, receptors, and the gut microbiome highlight disease-specific molecular interactions. To assess the diagnostic potential of these molecular signatures, a two-step analysis involving principal component analysis (PCA) and Random Forest classification was conducted, achieving accuracies of 75% for ALF and 89% for NAFLD. Additionally, machine learning algorithms, including K-neighbors, multi-layer perceptron (MLP), decision tree, Random Forest, logistic regression, gradient boosting, CatBoost, Extreme Gradient Boosting (XGB), and Light Gradient Boosting Machine (LGBM), were applied to gene expression data for ALF and NAFLD.</div></div><div><h3>Results</h3><div>Key genes including CLDN14, EGFR, GSK3B, MYC, and TJP2, alongside regulatory miRNAs let-7a-5p, miR-124-3p, and miR-195-5p and transcription factors NFKB1 and SP1 may be suggested as critical to liver disease progression. Additionally, gut microbiota members, Dictyostelium discoideum and Eikenella might be novel candidates associated with liver disease, highlighting the importance of the gut-liver axis. The Random Forest model reached 75% accuracy and 83% area under the curve for ALF, while NAFLD classification achieved 100% accuracy, precision, recall, and area under the curve underscoring robust diagnostic potential.</div></div><div><h3>Conclusion</h3><div>This study establishes a solid foundation for further research and therapeutic advancement by identifying key biomolecules and pathways critical to liver disease. Additional experimental validation is needed to confirm clinical applicability.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102552"},"PeriodicalIF":3.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Options for the Management of the Cholestatic Phase of Viral Hepatitis A and E—A Systematic Review","authors":"Suprabhat Giri ,&nbsp;Gaurav Khatana ,&nbsp;Prasanna Gore ,&nbsp;Dibya L. Praharaj ,&nbsp;Anand V. Kulkarni ,&nbsp;Anil C. Anand","doi":"10.1016/j.jceh.2025.102557","DOIUrl":"10.1016/j.jceh.2025.102557","url":null,"abstract":"<div><h3>Background/Aims</h3><div>The cholestatic hepatitis associated with acute viral hepatitis leads to prolonged jaundice and pruritus. While several treatment approaches have been proposed, there is a noticeable absence of agreement over the most effective course of action. The goal of this systematic review is to compile and assess the available data on treatment approaches for prolonged hepatitis associated with viral hepatitis.</div></div><div><h3>Methods</h3><div>We comprehensively searched for relevant studies in MEDLINE, Embase, and Scopus from their inception to May 2024. Studies reporting the treatment option for the management of the cholestatic phase associated with viral hepatitis were included.</div></div><div><h3>Results</h3><div>A total of 28 studies describing 164 patients were included in the review, of which 18 were case reports, 8 were case series, and 2 were interventional studies. The benefit of ursodeoxycholic acid (UDCA) was reported in two case reports, with doses varying from 10 to 30 mg/kg/d in the included studies. The use of corticosteroids in adult patients was reported in 21 studies, with prednisolone doses varying from 30 to 60 mg/day in adults. Two studies used nasobiliary drain (NBD) for patients who failed to respond to conventional therapy. Lastly, three studies reported using plasma exchange (PLEX) in patients refractory to standard treatment.</div></div><div><h3>Conclusion</h3><div>Patients not responding to UDCA or cholestyramine may benefit from a short course of corticosteroids, suggesting an immune-mediated phenomenon. NBD placement or PLEX may be tried after analyzing the risk-to-benefit ratio for patients who are nonresponsive to corticosteroids. Further research is required to determine the optimal treatment strategy.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102557"},"PeriodicalIF":3.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world Prevalence of Hepatitis B Reactivation in Patients With Resolved Hepatitis B Receiving Rituximab and Non-rituximab-based Immunosuppressive Therapy Without Chemoprophylaxis","authors":"Valerie Yeap,&nbsp;Wei-Lun Liou,&nbsp;Gayathry Morvil,&nbsp;Rajneesh Kumar","doi":"10.1016/j.jceh.2025.102551","DOIUrl":"10.1016/j.jceh.2025.102551","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis B virus reactivation (HBVr) can occur in patients with resolved hepatitis B virus (HBV) infection receiving immunosuppressive therapy. The class of immunosuppression influences HBV reactivation (HBVr) risk, with B-cell depleting agents such as Rituximab conferring a higher risk. The presence of hepatitis B surface antibodies (HBsAb) may be protective against HBVr.</div></div><div><h3>Objective</h3><div>To compare the rates of HBVr amongst individuals with resolved HBV infection receiving rituximab and non-rituximab immunosuppressive therapy, without chemoprophylaxis. Our secondary objective was to explore the role of HBsAb in risk stratification for HBVr.</div></div><div><h3>Methods</h3><div>We retrospectively collected the data of patients with resolved HBV infection receiving immunosuppressants between 2014 and 2022. HBVr rates amongst patients receiving rituximab and non-rituximab therapy were compared. Logistic regression analysis was performed to identify risk factors for HBVr.</div></div><div><h3>Results</h3><div>148 patients with resolved HBV infection did not receive chemoprophylaxis. Of the 20 (13.5%) patients who developed HBVr, none developed HBV flare. 42 of the 148 (28.3%) patients received rituximab-based therapy. Patients who received rituximab had a higher risk of HBVr, 12(28.6%) vs 8(7.5%), <em>P</em> = 0.001. This was confirmed on multivariable analysis (OR 4.19 [C.I. 1.47–11.9], <em>P</em> = 0.007). HBsAb titres of above 100 mIU/ml were protective against HBVr (OR 0.04 [CI 0.001–0.84], <em>P</em> = 0.039) in the rituximab exposed cohort, but not in the non-rituximab exposed cohort.</div></div><div><h3>Conclusion</h3><div>The risk of HBVr was higher in patients receiving rituximab; however, no patient developed HBV flare. In patients with resolved HBV infection, the presence of HBsAb titres above 100 mIU/ml may confer additional protection against HBVr and can be used as part of risk stratification for HBVr. In such patients, close surveillance with on-demand therapy instead of chemoprophylaxis may be considered.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102551"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Bile Acid Elevation is an Independently Associated With Pruritus in Patients With At-risk Metabolic Dysfunction-associated Steatotic Liver Disease","authors":"Zobair M. Younossi ,&nbsp;Michael J. Estep ,&nbsp;Sean Felix ,&nbsp;Brian Lam ,&nbsp;Sumanta Mukherjee ,&nbsp;Brandon Swift ,&nbsp;Linda Casillas ,&nbsp;Andrea R. de Souza ,&nbsp;Jake Hunnicutt ,&nbsp;Megan M. McLaughlin ,&nbsp;Andrei Racila ,&nbsp;Fatema Nader ,&nbsp;Maria Stepanova","doi":"10.1016/j.jceh.2025.102549","DOIUrl":"10.1016/j.jceh.2025.102549","url":null,"abstract":"<div><h3>Background and aims</h3><div>Elevated serum bile acids are associated with pruritus in cholestatic liver diseases. We assessed the association of serum bile acids and other putative biomarkers of cholestatic pruritus (autotaxin and interleukin-31 (IL-31) with pruritus in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).</div></div><div><h3>Methods</h3><div>We used serum from patients with MASLD and metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis B, viral hepatitis C, and healthy blood donors to measure the levels of bile acids, autotaxin, and IL-31. Clinically significant pruritus was defined from the Chronic Liver Disease Questionnaire.</div></div><div><h3>Results</h3><div>Six hundred fifty-one subjects were included [MASLD (N = 497, 88 MASH), viral hepatitis B and C (VH, N = 98), healthy controls (N = 56)]. Post hoc definitions of high biomarker levels associated with the presence of clinically significant pruritus were as follows: high bile acids ≥5.9 μmol/L, high autotaxin ≥220 ng/mL, and high IL-31 ≥ 25 pg/mL. The VH patients had the highest bile acids levels and lowest levels were in healthy controls (<em>P</em> &lt; 0.0001). The highest autotaxin levels were seen in hepatitis C, while the highest IL-31 levels in MASH. MASH patients had higher levels of all three biomarkers than non-MASH-MASLD. Also, at-risk MASLD or MASLD with advanced fibrosis (AF) had higher bile acids and autotaxin (all <em>P</em> &lt; 0.01) but not IL-31 (<em>P</em> &gt; 0.05). MASLD patients with high bile acids had more pruritus (all MASLD: 25% vs. 17%; MASH 30% vs. 13%; at-risk MASLD: 33% vs. 12%; AF: 41% vs. 8%). In multivariable logistic regressions, having high bile acids was an independent predictor of pruritus in at-risk MASLD [odds ratio (OR) (95% CI) = 4.4 (1.6–12.1)] and MASLD with advanced fibrosis [OR = 7.5 (2.0–29.0)]; but not autotaxin or IL-31 (all <em>P</em> &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>High serum bile acid level is independently associated with pruritus in at-risk MASLD.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102549"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis","authors":"Syed H. Ali ,&nbsp;Muhammad H. Shah ,&nbsp;Sakshi Roy ,&nbsp;Hareesha R. Bharadwaj ,&nbsp;Joecelyn K. Tan ,&nbsp;Medha S. Rao ,&nbsp;Muhtasim Fuad ,&nbsp;Arjun Ahluwalia ,&nbsp;Aditya Gaur ,&nbsp;Priyal Dalal ,&nbsp;Arkadeep Dhali ,&nbsp;Harishankar Gopakumar","doi":"10.1016/j.jceh.2025.102541","DOIUrl":"10.1016/j.jceh.2025.102541","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Chronic hepatitis B virus remains a significant cause of liver disease in the developing world, leading to sequelae such as hepatocellular carcinoma. While entecavir (ETV) serves as a first-line treatment, its growing resistance rates underscore the need to explore viable alternatives. Tenofovir disoproxil fumarate (TDF) monotherapy and entecavir plus tenofovir (TDF + ETV) combination therapy are both employed as treatments, but one's efficacy over another is in question. This meta-analysis aims to investigate any primacy of either treatment.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive literature search across PubMed/Medline, Embase, Cochrane Central, Web of Science, and China National Knowledge Infrastructure from inception till 7th October 2024. Studies comparing the safety and efficacy of TDF monotherapy versus TDF + ETV combination therapy in patients resistant to entecavir were considered. Data about the virologic response (VR), virologic breakthrough, HbeAg seroconversion, HbeAg/HbsAg seroclearance, and alanine aminotransferase normalization were extracted. Relative risks (RRs) and their corresponding 95% confidence intervals (CIs) were calculated, pooled, and analyzed in a random-effects model. <em>P</em>-value &lt;0.05 was regarded as significant for all analyses.</div></div><div><h3>Results</h3><div>Nine studies, comprising 335 patients undergoing monotherapy and 352 patients undergoing combination therapy, satisfied the criteria. TDF + ETV combination therapy was found slightly advantageous to TDF monotherapy, stimulating a VR at 48 weeks (RR 1.081 95% CI: [1.001–1.167] <em>P</em> = 0.046, I2 = 0%), along with the HbeAg seroconversion rate (RR 1.711 95% CI: [1.005–2.913] <em>P</em> = 0.048, I2 = 0%). There were no significant adverse events in individual studies to warrant a meta-analysis.</div></div><div><h3>Conclusions</h3><div>TDF + ETV shows slightly better efficacy to TDF monotherapy over a 48-week treatment regimen, with minimal safety concerns. However, further high-quality studies like randomized controlled trials are needed to further solidify conclusions, with this meta-analysis only achieving borderline significances.</div></div><div><h3>Registration</h3><div>This review is registered on the PROSPERO database (ID: CRD42024581443).</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102541"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}