Journal of Clinical and Experimental Hepatology最新文献

{"title":"Efficacy, Safety, and Tolerability of Farnesoid X Receptor Agonists in the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease: A Systematic Review and Meta-analysis","authors":"Joel G.K. Mekontso ,&nbsp;Joseph Y.B. Nnang ,&nbsp;Ticha B.T. Tembi ,&nbsp;Anifatou B. Kortim ,&nbsp;Guy L. Nguefang ,&nbsp;Justin Wagner ,&nbsp;Michael Bernstein","doi":"10.1016/j.jceh.2025.102563","DOIUrl":"10.1016/j.jceh.2025.102563","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease. Farnesoid X receptor (FXR) agonists are emerging as promising therapies for fibrosis, steatosis, and metabolic dysfunctions. However, its efficacy and safety remain unclear.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Embase, and Cochrane databases identified randomized controlled trials (RCTs) comparing FXR agonists with placebo in patients with MASLD. The main outcomes included improvement in fibrosis without worsening steatohepatitis, changes in liver chemistry and lipid profiles, and liver fat content (LFC). The safety outcomes assessed included side effects and treatment discontinuation rates. Heterogeneity was evaluated using I² statistics, with a random-effects model applied to the pooled analyses.</div></div><div><h3>Results</h3><div>Ten RCTs involving 3,779 patients were included, of which 2,527 (67%) were randomized to receive FXR agonists. FXR agonists significantly improved fibrosis by ≥ 1 stage (RR, 1.52; 95% CI: [1.23, 1.88]; <em>P</em> &lt; 0.0001) and reduced LFC (mean difference: −4.9%; 95% CI: [−8.26, −1.55]; <em>P</em> &lt; 0.001). A higher proportion of patients achieved a ≥30% reduction in LFC (42.8% vs. 18.4%; RR, 2.42; 95% CI: [1.69, 3.46]; <em>P</em> &lt; 0.00001). Significant reductions in alanine aminotransferase and gamma glutamyltransferase levels were observed, whereas alkaline phosphatase levels were increased. FXR agonists were associated with a slight reduction in High-Density Lipoprotein (HDL) cholesterol levels and a higher incidence of pruritus (37.8% vs. 18.7%; RR, 2.67; 95% CI: [1.63, 4.38]; <em>P</em> &lt; 0.00001), leading to higher treatment discontinuation rates.</div></div><div><h3>Conclusion</h3><div>FXR agonists have the potential to improve fibrosis and steatosis in MASLD patients. However, safety concerns still remain. Further research is required to determine the long-term efficacy and tolerability of these drugs.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102563"},"PeriodicalIF":3.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864682","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":"The Role of Stereotactic Body Radiation Therapy in the Outcomes of Intrahepatic Recurrent Small Hepatocellular Carcinoma","authors":"Yongjie Shui ,&nbsp;Dongjun Dai ,&nbsp;Yang Yang ,&nbsp;Jia Yang ,&nbsp;Feng Xuan ,&nbsp;Haiyan Chen ,&nbsp;Lihong Liu ,&nbsp;Qianqian Yu ,&nbsp;Yinglu Guo ,&nbsp;Risheng Yu ,&nbsp;Jianying Lou ,&nbsp;Qichun Wei","doi":"10.1016/j.jceh.2025.102561","DOIUrl":"10.1016/j.jceh.2025.102561","url":null,"abstract":"<div><h3>Background and aim</h3><div>To retrospectively evaluate the role of stereotactic body radiation therapy (SBRT) played for the outcomes of intrahepatic recurrent small hepatocellular carcinoma (HCC).</div></div><div><h3>Methods</h3><div>We collected 51 intrahepatic recurrent ≤5 cm small HCC patients between January 2016 and December 2021. SBRT was given as 4–5 fractions with 32.5–50Gy. The baseline data of the patients and the radiotherapy strategy data were collected and survival analyses were performed among these factors. The outcomes comprised overall survival (OS), freedom from local progression (FFLP), and progression-free survival (PFS), with the 95% confidence interval (95%CI). The follow-up time was calculated from the date of the SBRT to the date of the last follow-up communication, hospitalization, or death. Survival analysis was conducted by the Kaplan–Meier methods and log-rank test.</div></div><div><h3>Results</h3><div>The median follow-up time was 48 months (range: 4.8–90). The 1-year, 3-year, and 5-year OS rates of the overall cohort were 95.9% (95%CI: 0.905–1.000), 84.9% (95%CI: 0.751–0.959) and 69.1% (95%CI: 0.553–0.862), respectively. The 1-year, 3-year, and 5-year FFLP rates of the overall cohort were 97.5% (95%CI: 0.928–1.000), 82.0% (95%CI: 0.697–0.965), and 72.8% (95%CI: 0.578–0.918), respectively. The 1-year, 3-year, and 5-year PFS rates of the overall cohort were 85.7% (95%CI: 0.758–0.970), 43.4% (95%CI: 0.296–0.635), and 27.3% (95%CI: 0.149–0.498), respectively. The 5-year FFLP rate of lesions less than 2 cm [72.5% (95%CI: 0.52–1)] and those 2–5 cm [71.9% (95%CI: 0.514–0.976)] were similar. We suggested that the lesions received 45Gy/50Gy with 5 fractions were associated with a higher 5-year FFLP rate [74.6% (95%CI: 0.57–0.976)] than 40Gy/5F [40.0% (95%CI: 0.137–1)].</div></div><div><h3>Conclusion</h3><div>We found SBRT was effective in patients with lesion size of 2–5 cm, with similar results in those with tumor size of 0–2 cm. We suggested that the lesions received over 85.5Gy of biological effective dose with α/β = 10Gy were associated with a higher FFLP.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102561"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848555","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":"Indian National Association for the Study of Liver (INASL) Guidance Statements for Determining Futility in Liver Transplantation","authors":"Anil Arora ,&nbsp;Praveen Sharma ,&nbsp;Ashish Kumar ,&nbsp;S.K. Acharya ,&nbsp;Shiv K. Sarin ,&nbsp;Ajay Duseja ,&nbsp;Pankaj Puri ,&nbsp;Samir Shah ,&nbsp;Y.K. Chawla ,&nbsp;P.N. Rao ,&nbsp;Anoop Saraya ,&nbsp;Ravi Mohanka ,&nbsp;Shweta Singh ,&nbsp;Sanjeev Saighal ,&nbsp;Mohamed Rela ,&nbsp;Vivek Vij ,&nbsp;Sonal Asthana ,&nbsp;Akash Shukla ,&nbsp;Prashant Bhangui ,&nbsp;Neeraj Saraf ,&nbsp;Naimish Mehta","doi":"10.1016/j.jceh.2025.102539","DOIUrl":"10.1016/j.jceh.2025.102539","url":null,"abstract":"<div><div>Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102539"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873501","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":"Predictive Factors and Nomogram (MAP-BNP) for Post Stereotactic Body Radiotherapy Survival in Advanced Hepatocellular Carcinoma Patients","authors":"Deepti Sharma ,&nbsp;Babu Lal Meena ,&nbsp;Hanuman Prasad Yadav ,&nbsp;Guresh Kumar ,&nbsp;Anju K. V ,&nbsp;Deepak Jagya ,&nbsp;Shiv Kumar Sarin","doi":"10.1016/j.jceh.2025.102555","DOIUrl":"10.1016/j.jceh.2025.102555","url":null,"abstract":"<div><h3>Background</h3><div>Stereotactic body radiation therapy (SBRT) is a widely recognized approach for managing hepatocellular carcinoma (HCC), particularly in its advanced stages, with prognosis highly dependent on tumour burden and baseline liver function. This study aimed to develop a predictive model and nomogram that incorporates these factors to improve survival outcomes in advanced HCC patients treated with SBRT and systemic therapy.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed records of 110 patients with advanced HCC treated with SBRT between May 2020 and April 2023. Inclusion criteria included age ≥18 years, cirrhosis, and suitability for SBRT.</div></div><div><h3>Results</h3><div>The median age was 63 years (range 28–84), with viral cirrhosis (40.9%) and NASH (38.2%) as the main aetiologies. At presentation, 83.6% of patients had portal vein thrombosis, 32.7% had nodal metastasis, and 50% had distant metastasis. The median tumour diameter was 9 cm, and 73.6% of patients had the multifocal disease.</div><div>A median SBRT dose of 35 Gy (range 25–45 Gy) in 5 fractions was administered. Significant reductions in tumour markers were noted at three months: AFP levels dropped from a median of 309.75 ng/ml to 62 ng/ml (<em>P</em> = 0.015), and PIVKA II from 2230 mAU/ml to 345 mAU/ml (<em>P</em> = 0.001). Complete and partial responses were seen in 33% and 45% of patients, respectively. The median overall survival (OS) was 14 months (95% CI 11.7–16.2), with OS rates of 90%, 58%, and 34% at 6, 12, and 24 months. Progression-free survival (PFS) was 9 months (95% CI 6.4–11.5). Significant predictors of OS included multifocal tumour, portal vein thrombosis, lymph node involvement, serum bilirubin, serum albumin, and log PIVKA-II. The developed MAP-BNP nomogram achieved a C-index of 0.853, outperforming the Child-Turcotte-Pugh (0.62) and ALBI (0.64) scores. Patients were classified into low-risk (&lt;200 points) and high-risk (&gt;200 points) groups, with the low-risk group showing a significantly longer OS (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>The MAP-BNP nomogram, integrating tumour burden and liver function, provides a more individualized approach for predicting survival in advanced HCC patients treated with SBRT and systemic therapy, outperforming traditional staging systems.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102555"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844959","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":"Liver Transplantation for Non-hepatocellular Carcinoma: The Role of Immune Checkpoint Inhibitors","authors":"Pegah Bahrami ,&nbsp;Mohammad Al Zein ,&nbsp;Ali H. Eid ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.jceh.2025.102558","DOIUrl":"10.1016/j.jceh.2025.102558","url":null,"abstract":"<div><div>Colorectal cancer (CRC), gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), and cholangiocarcinoma (CCA) exhibit high rates of morbidity and mortality once metastasized to the liver. Liver transplantation (LT) is a viable therapeutic approach for these cancers in highly selected patients; however, their invasive nature at late stages causes many patients to be delisted from transplantation or to require further downstaging. Immunotherapy with immune checkpoint modulators has revolutionized cancer research. Immune checkpoint inhibitors (ICI) leverage the chronic inflammatory state and the overexpression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) by malignant cells and regulatory T cells, to block immune checkpoints and counteract tumor's ability to evade the immune system. However, the interaction between allograft PD-L1 and PD-1 on infiltrating T cells functions as a means of graft tolerance in cases of LT. Therefore, the application of ICIs might block this protective effect and induce graft rejection, a phenomenon particularly observed in PD-1/PD-L1 inhibiting ICIs. The risk of post-LT graft rejection can be mitigated by applying advanced biomarkers and specifying certain mutations that enhance patient selection criteria for pre-LT ICI use. Furthermore, the determination of optimal intervals of ICI administration pre- and post-LT, identification of ICI indications in <em>de novo</em> malignancies occurring after LT, and investigation of biomarkers for early rejection detection, pave the way for more promising LT outcomes in patients with CRC, GEP-NEN, or CCA. Therefore, this review aims to illustrate a comprehensive overview of the role of ICI therapy in the management of non-hepatocellular carcinoma transplant oncology cancers by demonstrating the potential for its application in both pre-and post-LT states, and pathways to reduce or timely detect ICI-associated graft rejection.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102558"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844960","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":"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":"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}