Journal of Clinical and Experimental Hepatology最新文献

{"title":"Validation of a Multiplex Hypermethylation-based Blood Test to Detect Hepatocellular Carcinoma: A Prospective Case-control Study","authors":"Ashwin Rammohan ,&nbsp;Dinesh Jothimani ,&nbsp;Kunkumabalasubramanian Sreedurgalakshmi ,&nbsp;Mohammed Farouk ,&nbsp;Srinivasan Lakshmi ,&nbsp;G. Vasanthakumar ,&nbsp;Simon Evangeline ,&nbsp;Komalavalli Subbiah ,&nbsp;Mukul Vij ,&nbsp;Jeyanthi Rebecca ,&nbsp;Srikar Raman ,&nbsp;Mohamed Rela","doi":"10.1016/j.jceh.2025.102578","DOIUrl":"10.1016/j.jceh.2025.102578","url":null,"abstract":"<div><h3>Background/Aims</h3><div>This study aimed to evaluate the performance of an investigational multiplex hypermethylation-based HCC screening test (mhsH) in the detection of hepatocellular carcinoma (HCC) using blood samples.</div></div><div><h3>Methods</h3><div>Adult patients with chronic liver disease (CLD) were enrolled in this prospective case-control study. For the mhsH test, blood samples were collected, and the cell-free DNA obtained from the samples was analyzed for methylation patterns using multiplex droplet digital polymerase chain reaction. The performance of the mhsH test for the detection of HCC was evaluated according to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve and a comparative analysis with alpha-fetoprotein (AFP) was performed. Radiological imaging was used as the clinical reference standard.</div></div><div><h3>Results</h3><div>A total of 649 participants were screened for recruitment, and the mhsH test performance assessment was carried out for 588 patients with complete local data, comprising 142 patients in the HCC group and 446 in the non-HCC CLD control group. The test demonstrated robust HCC signal detection, achieving an AUC of 0.91 (95% confidence interval [CI]: 0.88-0.94). The sensitivity and specificity were 0.91 (0.85-0.95) and 0.88 (0.85-0.91), with PPV and NPV of 0.71 (0.66-0.76) and 0.97 (0.95-0.98), respectively. The sensitivity of early-stage, intermediate-stage, and late-stage (Barcelona Clinic Liver Cancer) was 0.87 (73-0.96), 0.91 (0.77-0.98), and 0.94 (0.82-0.99), respectively. The test correctly identified 57 of 62 (92%) patients with AFP-negative HCC. Combining AFP with the mhsH test increased sensitivity to 0.96 (0.92-0.99).</div></div><div><h3>Conclusion</h3><div>The mhsH test demonstrated high accuracy for detecting HCC signals. Furthermore, when combined with AFP, the test performance for detecting HCC in patients with CLD has significantly improved.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102578"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916106","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":"Feasibility, Safety and Efficacy of Transjugular Intrahepatic Portosystemic Shunt for the Management of Portal Vein Thrombosis in Cirrhosis","authors":"Andrés Conthe ,&nbsp;Luis Ibañez-Samaniego ,&nbsp;Enrique Calleja ,&nbsp;Paula Saralegui ,&nbsp;Arturo Álvarez-Luque ,&nbsp;Miguel-Jesús Echenagusia ,&nbsp;Manuel González-Leyte ,&nbsp;Fernando Carretero ,&nbsp;Carlos Ballano ,&nbsp;José-Ángel López-Baena ,&nbsp;Diego Rincón ,&nbsp;María-Vega Catalina ,&nbsp;Rafael Bañares","doi":"10.1016/j.jceh.2025.102580","DOIUrl":"10.1016/j.jceh.2025.102580","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Anticoagulation is considered the standard of care for portal vein thrombosis (PVT) in cirrhosis; however, a significant number of patients cannot be safely treated or exhibit thrombus progression despite anticoagulation. We evaluated the role of transjugular intrahepatic portosystemic shunt (TIPS) when indicated exclusively as treatment of PVT in cirrhosis.</div></div><div><h3>Methods</h3><div>A retrospective study was conducted including all cirrhotic patients with nontumoral PVT treated with TIPS in a tertiary care center. Patients with PVT and additional indications for TIPS were excluded. Feasibility, safety, and efficacy were analyzed. TIPS outcomes compared with a contemporary cohort of patients with TIPS indicated for refractory ascites.</div></div><div><h3>Results</h3><div>A total of 243 patients were treated by TIPS during the study period, 30 of whom underwent the procedure solely to achieve portal vein recanalization. Portal cavernoma was present in 40% of patients, and 53% of the patients had Yerdel 3 or 4 PVT. Main indications for TIPS were contraindication (53%) or a lack of response (30%) to anticoagulant therapy. In 17% of cases, TIPS was indicated to facilitate liver transplantation (LT) when PVT precluded portal anastomosis. TIPS was successful in 96.6% of patients. Major complications (2 patients) and shunt-related events after TIPS were similar to those reported in the control group. Seventeen percent of patients showed TIPS dysfunction (all successfully treated), a rate similar to that reported in patients with refractory ascites. A higher post-TIPS portacaval pressure gradient was associated with a greater risk of dysfunction. The main portal vein trunk remained patent in all patients, 8 of whom received uneventful LT.</div></div><div><h3>Conclusion</h3><div>TIPS can be safely performed in patients with cirrhosis and PVT, with an indication for recanalization if medical therapy has failed or is contraindicated.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102580"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941295","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":"Carbapenem-resistant Enterobacteriaceae Colonization and Impact on Outcomes in Cirrhosis","authors":"Venishetty Shantan,&nbsp;Kalyan Rakam,&nbsp;Amarthya Sree Racha,&nbsp;Sadhana Y. Veturi,&nbsp;Anand Gupta,&nbsp;Anand V. Kulkarni","doi":"10.1016/j.jceh.2025.102576","DOIUrl":"10.1016/j.jceh.2025.102576","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102576"},"PeriodicalIF":3.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911950","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-related Events and Outcomes in Patients With Metabolic Dysfunction-associated Steatotic Liver Disease Varies With the Type of Cardiometabolic Risk Factor","authors":"Shekhar Swaroop,&nbsp;Sagnik Biswas,&nbsp;Shubham Mehta,&nbsp;Arnav Aggarwal,&nbsp;Umang Arora,&nbsp;Samagra Agarwal,&nbsp;Amitkumar Chavan,&nbsp;Baibaswata Nayak,&nbsp;Shalimar","doi":"10.1016/j.jceh.2025.102559","DOIUrl":"10.1016/j.jceh.2025.102559","url":null,"abstract":"<div><h3>Background</h3><div>The long-term impact of individual cardiometabolic risk factors (CMRFs) and their combinations on outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains poorly defined.</div></div><div><h3>Methods</h3><div>In this single-center retrospective analysis, all consecutive patients diagnosed with MASLD from August 2001 to January 2024 were included. CMRFs were defined as per established criteria, with body mass index threshold of 23 kg/m². Liver-related events (LREs) included ascites, hepatic encephalopathy (HE), variceal bleeding, hepatocellular carcinoma, and liver-related mortality. Rates of LREs and mortality were compared across CMRF combinations, and predictors were evaluated.</div></div><div><h3>Results</h3><div>Of 1395 screened patients, 1043 were analyzed (median follow-up: 5.3 (3.8–6.7) years). LREs occurred in 30 (2.9%) patients, with an incidence of 5.04 (3.48–7.30) per 1000 person-years (PY). All-cause mortality occurred in 32 (3.0%) patients, with an incidence of 5.36 (95% CI: 3.79–7.58) per 1000 PY, including 14 (1.3%) liver-related mortality. Among individual CMRFs, diabetes was associated with the greatest proportion of mortality (4.1%), LREs (7.0%), and extrahepatic events (4.5%), while dyslipidemia was associated with the lowest proportions (2.4%, 2.4% and 2.2%, respectively). Patients with all five CMRFs had the highest rates of all-cause mortality (13.6 per 1000 PY) and LREs (8.8 per 1000 PY), though these differences were not statistically significant compared to those with fewer CMRFs. When assessing CMRF combinations, those with hypertension, low high density lipoprotein, obesity, and diabetes had the highest LRE (17.4 per 1000 PY) and all-cause mortality (21.1 per 1000 PY). Liver stiffness measurement (LSM) ≥10 kPa was an independent predictor of LRE and all-cause mortality.</div></div><div><h3>Conclusion</h3><div>The type of CMRF plays a more critical role than the number of CMRFs in determining MASLD outcomes. Among the CMRFs, diabetes is associated with higher rates of LREs and deaths in patients with MASLD. LSM ≥10 kPa is a key predictor of clinical outcomes.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102559"},"PeriodicalIF":3.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916105","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, 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":"Immunohistochemistry in Progressive Familial Intrahepatic Cholestasis (PFIC): Bridging Gap Between Morphology and Genetics","authors":"Neha Nigam ,&nbsp;Chhagan Bihari ,&nbsp;Moinak S. Sarma ,&nbsp;Anshu Srivastava ,&nbsp;Narendra Krishnani ,&nbsp;Prabhakar Mishra","doi":"10.1016/j.jceh.2025.102562","DOIUrl":"10.1016/j.jceh.2025.102562","url":null,"abstract":"<div><h3>Background/Aims</h3><div>A heterogeneous group of disorders caused by bile secretion and transport defects is progressive familial intrahepatic cholestasis (PFIC). PFIC has various subtypes with different presentations, laboratory findings, treatments, progression, and prognosis. Genetic analysis is the gold standard for diagnosis but is costly, time-consuming, and not readily available. In this study, immunohistochemistry (IHC) was evaluated as a tool for identifying subtypes of PFIC and differentiating them from other causes of pediatric cholestasis.</div></div><div><h3>Methods</h3><div>The study included genetically confirmed PFIC (n = 40) and non-PFIC group (n = 20). Clinical history and laboratory investigations were recorded from the hospital information system. PFIC subtypes 1,2,3,4,5, and 6 showed the genetic mutation in ATP8B1, ABCB11, ABCB4, tight junction protein 2 (TJP2), NR1H4, and MYO5B, respectively. IHC has been applied for bile salt export pump (BSEP), multidrug resistance protein 3 (MDR3), TJP2, Claudin 1, farnesoid X receptor (FXR), and MYO5B.</div></div><div><h3>Results</h3><div>IHC staining for BSEP, MDR3, TJP2, and MYO5B was positive in 100% of PFIC 1 and negative in 90.9%, 84.6%, 100%, and 100%, respectively, of the PFIC subtypes 2, 3, 4, and 6. Significant differences were noted between PFIC and non-PFIC patients for BSEP (<em>P</em> = 0.044), MDR3 (<em>P</em> = 0.022), and TJP2 (<em>P</em> &lt; 0.001). In comparison with the non-PFIC patients, BSEP’s sensitivity and specificity for diagnosing PFIC 2 was 90.9% and 95%, MDR3’s for diagnosing PFIC 3 was 84.6% and 95%, TJP2 for PFIC 4 was 100% and 95%, and MYO5B’'s for PFIC 6.</div></div><div><h3>Conclusion</h3><div>Immunostaining for the markers BSEP, MDR3, TJP2, and MYO5B can differentiate various PFIC subtypes and distinguish between PFIC and non-PFIC patients.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 5","pages":"Article 102562"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891069","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}