Journal of Clinical and Experimental Hepatology最新文献

{"title":"Role of Steatosis in Preventing Post-hepatectomy Liver Failure After Major Resection: Findings From an Animal Study","authors":"Andrea Lund ,&nbsp;Mikkel T. Thomsen ,&nbsp;Jakob Kirkegård ,&nbsp;Anders R. Knudsen ,&nbsp;Kasper J. Andersen ,&nbsp;Michelle Meier ,&nbsp;Jens R. Nyengaard ,&nbsp;Frank V. Mortensen","doi":"10.1016/j.jceh.2024.102453","DOIUrl":"10.1016/j.jceh.2024.102453","url":null,"abstract":"<div><h3>Background/Aim</h3><div>Post-hepatectomy liver failure (PHLF) and hepatic steatosis are evident shortly after extensive partial hepatectomy (PH) in rodents. This study aimed to extrapolate the protein expression and biological pathways involved in recovering PHLF (rPHLF) and non-recovering PHLF (nrPHLF).</div></div><div><h3>Methods</h3><div>Rats were randomly assigned to 90% PH or sham surgery. rPHLF was distinguished from nrPHLF using a quantitative scoring system. The sham (n = 6), rPHLF (n = 8), and nrPHLF (n = 13) groups were compared 24 h post-PH. Proteomics was used to assess protein variations and to investigate differentially regulated biological pathways. Stereological methods were used to quantify hepatic lipid content. The plasma triglyceride levels were measured.</div></div><div><h3>Results</h3><div>rPHLF demonstrated substantial downregulation of proteins involved in lipid metabolism compared to nrPHLF (<em>P</em> &lt; 0.001). Several proteins associated with lipogenesis, beta-oxidation, lipolysis, membrane trafficking, and inhibition of cell proliferation were markedly downregulated in rPHLF.</div><div>The hepatic lipid proportion was significantly higher for rPHLF (61% of hepatocyte volume, 95% confidence interval [CI]: 48%–82%) than for nrPHLF (32% of hepatocyte volume, 95% CI: 22%–39%). The median lipid volume per hepatocyte in rPHLF was 2815 μm³ (95% CI: 2208–3774 μm³) and 1759 μm³ in nrPHLF (95% CI: 1188–2134 μm³). Lipid droplets were not detected in the sham-operated rats. No significant differences in plasma triglyceride levels were found between the groups (<em>P</em> &gt; 0.08).</div></div><div><h3>Conclusion</h3><div>The degree of hepatic steatosis is a promising prognostic indicator for early liver regeneration and nrPHLF onset immediately following extensive PH. Intrahepatic lipid accumulation appears to be linked to the coordinated downregulation of proteins integral to lipid metabolism and cellular transport.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102453"},"PeriodicalIF":3.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Preoperative Recipient Portal Vein Thrombosis in Living-donor Liver Transplantation","authors":"Vivek Rajendran,&nbsp;Danny Joy,&nbsp;Sudheer Mohammed,&nbsp;Biju Chandran,&nbsp;Mathew Jacob","doi":"10.1016/j.jceh.2024.102445","DOIUrl":"10.1016/j.jceh.2024.102445","url":null,"abstract":"<div><div>Portal vein thrombosis (PVT) occurs as a part of the natural history of cirrhosis in up to 15% of patients with cirrhosis. In the initial days, PVT was considered a contraindication to liver transplantation, but now with advanced techniques and perioperative management, patients with complex PVT also undergo living-donor liver transplantation (LDLT) with a similar outcome. This review provides a comprehensive overview of methods to proceed with liver transplantation when the recipient has PVT. Preoperatively, anticoagulation remains the mainstay of treatment, with transjugular intrahepatic portosystemic shunt (TIPS) playing an adjunct role in preparing patients for liver transplantation. In all patients, thrombectomy with re-establishment of physiological portal flow is the initial step. In patients where flow cannot be established, other physiological or nonphysiological means are employed, especially in complex PVT. Patients with grade III/IV PVT have worse outcomes (graft failure, mortality, recurrence) than those with lower-grade PVT. Physiological reconstruction is the method of choice, whereas non-physiological means are used as a bailout procedure.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102445"},"PeriodicalIF":3.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971043","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":"Genes of DLK1-DIO3 Locus and miR-379/656 Cluster is a Potential Diagnostic and Prognostic Marker in Patients With Hepatocellular Carcinoma: A Systems Biology Study","authors":"Shreyas H. Karunakara ,&nbsp;Rohit Mehtani ,&nbsp;Shama P. Kabekkodu ,&nbsp;Divya P. Kumar ,&nbsp;Prasanna K. Santhekadur","doi":"10.1016/j.jceh.2024.102450","DOIUrl":"10.1016/j.jceh.2024.102450","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma is the sixth most common malignancy reported globally. This highlights the need for reliable biomarkers that can be employed for diagnostic and prognostic applications. The present study aimed to classify and characterize the clinical potential of delta like non-canonical Notch ligand 1–type III iodothyronine deiodinase (DLK1-DIO3) and miR-379/656 cluster genes in hepatocellular carcinoma.</div></div><div><h3>Methods</h3><div>We extensively studied the clinical potential of DLK1-DIO3 genes through a comprehensive systems biology approach and assessed the diagnostic and prognostic potential of the genes associated with the region. Additionally, we have predicted the gene targets of the miR-379/656 cluster associated with the locus and have identified the gene ontology, pathway, and disease associations.</div></div><div><h3>Results</h3><div>We report this region as a potential biomarker for hepatocellular carcinoma. About thirty clustered miRNAs, a long-non-coding RNA, and two coding genes of the region were underexpressed in tumors. The receiver operating characteristic analysis identified 11 clustered miRNAs with diagnostic potential. Survival analyses identified maternally expressed gene 3 and the miR-379/656 cluster as prognostically significant. Further, the random forest model predicted that the miRNA cluster classifies patients according to Tumor, Node, Metastasis (TNM) staging. Furthermore, overrepresentation analysis identified several key pathways, molecular functions, and biological processes associated with the cluster gene targets.</div></div><div><h3>Conclusion</h3><div>Our study suggests that DLK1-DIO3 genes, miR-379/656 cluster, and its target gene network might be potential diagnostic and prognostic markers for hepatocellular carcinoma management and therapy.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102450"},"PeriodicalIF":3.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743158","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":"Toward Rational Strategies for Prevention of Bleeding During Invasive Procedures in Patients With Cirrhosis","authors":"Ton Lisman","doi":"10.1016/j.jceh.2024.102452","DOIUrl":"10.1016/j.jceh.2024.102452","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 1","pages":"Article 102452"},"PeriodicalIF":3.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748023","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":"First Series of Living Donor Liver Retransplants From India: Challenges and Outcomes","authors":"Shaleen Agarwal ,&nbsp;Rajesh Dey ,&nbsp;Sanjiv Saigal ,&nbsp;Phani K. Nekarakanti ,&nbsp;Subash Gupta","doi":"10.1016/j.jceh.2024.102454","DOIUrl":"10.1016/j.jceh.2024.102454","url":null,"abstract":"<div><h3>Background</h3><div>There is a paucity of Indian data on long-term survival after living donor liver transplant (LDLT) or the need for retransplant (re-LT). In this article, we report the first series of retransplants from India with focus on indications, technical challenges and results.</div></div><div><h3>Methods</h3><div>A retrospective study on 29 patients undergoing a liver retransplant (re-LT) was analysed with respect to survival outcomes and postoperative complications. Patients were divided into early and late retransplant groups based on whether re-LT was performed within or beyond 30 days of primary transplant.</div></div><div><h3>Results</h3><div>Liver retransplant was performed in 29 (0.81%) patients out of a total of 3563 liver transplants (28 living donor and one deceased donor liver transplant). The primary transplant was an LDLT in 27 (93%) patients. Retransplant was performed at a median of 26 days after the first transplant. Re-LT was performed early (within 30 days) in 17 (59%) patients and late (beyond 30 days) in 12 (41%). Hepatic artery thrombosis (53%) and early graft dysfunction (47%) were the indications for early retransplant, while biliary complications (50%) and chronic rejection (33%) were primary indications for late retransplant. Postretransplant complications occurred in 22 (75%) patients, the commonest being gram-negative bacterial sepsis. The 30-day mortality after retransplant was 27% (8/29). The primary cause of mortality was gram-negative septicaemia. The mortality in the late retransplant group (2, 16.6%) was lower than in the early retransplant group (6, 35%).</div></div><div><h3>Conclusion</h3><div>Retransplant using living donors is a viable option in properly selected patients with prior LDLT.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102454"},"PeriodicalIF":3.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080201","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":"Issue Highlights","authors":"","doi":"10.1016/S0973-6883(24)01110-1","DOIUrl":"10.1016/S0973-6883(24)01110-1","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"14 6","pages":"Article 102443"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592726","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 SVIN-Trial—Just Another Brick in the Wall?","authors":"Rohit Mehtani","doi":"10.1016/j.jceh.2024.102449","DOIUrl":"10.1016/j.jceh.2024.102449","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102449"},"PeriodicalIF":3.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702458","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":"Global Epidemiology of Hepatocellular Carcinoma","authors":"Satender P. Singh,&nbsp;Tushar Madke,&nbsp;Phool Chand","doi":"10.1016/j.jceh.2024.102446","DOIUrl":"10.1016/j.jceh.2024.102446","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and a significant global health challenge due to its high mortality rate. The epidemiology of HCC is closely linked to the prevalence of chronic liver diseases, the predominant etiology being hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol consumption, and metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD). HCC incidence varies widely globally, with the highest rates observed in East Asia and sub-Saharan Africa. This geographic disparity is largely attributed to the endemicity of HBV and HCV in these regions. In Western countries, the incidence of HCC has been rising, driven by increasing rates of alcohol abuse and the presence of steatosis liver disease. MASLD-associated HCC has a higher body mass index, a higher rate of type 2 diabetes mellitus, hyperlipidemia, hypertension, and association with cardiovascular diseases. Steatosis-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related liver disease and viral hepatitis. Prevention strategies vary by region, focusing on vaccination against HBV, antiviral treatments for HBV and HCV, alcohol moderation, and lifestyle interventions along with weight reduction to reduce obesity and incidence of MASLD-related HCC incidence.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102446"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702456","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":"Safety and Effectiveness of Naltrexone in the Management of Alcohol Use Disorder in Patients With Alcohol-associated Cirrhosis: First Clinical Observation From Indian Cohort","authors":"Mohit Varshney ,&nbsp;Apinderjit Kaur ,&nbsp;Shiv K Sarin ,&nbsp;Saggere Muralikrishna Shasthry ,&nbsp;Vinod Arora","doi":"10.1016/j.jceh.2024.102447","DOIUrl":"10.1016/j.jceh.2024.102447","url":null,"abstract":"<div><h3>Background and aims</h3><div>Naltrexone is a promising drug to treat alcohol use disorder with limited evidence of safety in liver diseases. An observational study was performed to study the safety, effectiveness, and tolerability of Naltrexone in the management of alcohol use disorder in patients with alcohol-associated cirrhosis.</div></div><div><h3>Methods</h3><div>Naltrexone was started in patients with alcohol-related liver disease for the management of alcohol use disorder in 86 patients who were followed up for 4 weeks. Baseline liver parameters were compared with those at 4 weeks to establish safety of the drug. Effectiveness was determined by observing reduction in AUDIT scores, craving, number and days of drinking. Self-report of side effects was noted.</div></div><div><h3>Results</h3><div>After 4 weeks of starting Naltrexone there was a decrease in AST-89.86 vs 57.61, ALT-50.19 vs 27.08, SAP-121.81 vs 98.19, GGT-166.93 vs 109 and MELD 16.32 vs 12.13 (none statistically significant). There was a statistically significant reduction in Serum Bilirubin- (4.31 vs 1.98), INR (1.49 vs 1.32), self-reported craving (3.71 Vs 1.97; <em>P</em> = 0.01), AUDIT scores (24.13 Vs 16.91; <em>P</em> &lt;0.01) and number of drinking days in last one month (10.22 Vs 4.19; <em>P</em> = 0.03).</div></div><div><h3>Conclusion</h3><div>The reduction in all liver parameters and AUDIT scores and craving after treatment with Naltrexone supports its safety and utility in the management of alcohol use disorder in alcohol-related liver cirrhosis.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102447"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702455","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":"Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma","authors":"Prabhjyoti Pahwa ,&nbsp;Deepti Sharma ,&nbsp;Pushpa Yadav ,&nbsp;Sherin S. Thomas ,&nbsp;Sandhya Hora ,&nbsp;E. Preedia Babu ,&nbsp;Gayatri Ramakrishna ,&nbsp;Shiv K. Sarin ,&nbsp;Nirupama Trehanpati","doi":"10.1016/j.jceh.2024.102444","DOIUrl":"10.1016/j.jceh.2024.102444","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients.</div></div><div><h3>Methods</h3><div>We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded.</div></div><div><h3>Results</h3><div>The cohort had a median follow-up duration of 12.5 months (range 4–30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9–26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7–14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (<em>P</em> = 0.028) and VEGF-A (<em>P</em> = 0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (<em>P</em> = 0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (<em>P</em> = 0.326) in patients in whom HGF was reduced post-SBRT.</div></div><div><h3>Conclusion</h3><div>We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102444"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702457","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}