Pub Date : 2024-02-24DOI: 10.1016/j.jceh.2024.101372
Barath Jagadisan, Anil Dhawan
{"title":"Combination Treatment With Chelators and Zinc for Wilson Disease: A Double-edged Sword","authors":"Barath Jagadisan, Anil Dhawan","doi":"10.1016/j.jceh.2024.101372","DOIUrl":"https://doi.org/10.1016/j.jceh.2024.101372","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140069597","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}
Pub Date : 2024-02-23DOI: 10.1016/j.jceh.2024.101366
Ajay K. Patwa , Khushboo Yadav , Virendra Atam , Kauser Usman , Satyendra K. Sonkar , Shyam C. Chaudhary , Vivek Kumar , Kamal K. Sawlani , Kamlesh K. Gupta , Munna L. Patel , Dandu H. Reddy , Harish Gupta , Medhavi Gautam , Satish Kumar , Amit Kumar , Ambuj Yadav , Deepak Bhagchandani , Mahak Lamba , Abhishek Singh , Ajay K. Mishra
Background
Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients.
Methods
In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed.
Results
Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18–70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these.
Conclusion
The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.
{"title":"Comparison of a Novel Score “NOD−ACLF” to Other Established Prognostic Scores for Prediction of Mortality in APASL−ACLF Patients: A Cohort Study from a Tertiary Care Center of North India","authors":"Ajay K. Patwa , Khushboo Yadav , Virendra Atam , Kauser Usman , Satyendra K. Sonkar , Shyam C. Chaudhary , Vivek Kumar , Kamal K. Sawlani , Kamlesh K. Gupta , Munna L. Patel , Dandu H. Reddy , Harish Gupta , Medhavi Gautam , Satish Kumar , Amit Kumar , Ambuj Yadav , Deepak Bhagchandani , Mahak Lamba , Abhishek Singh , Ajay K. Mishra","doi":"10.1016/j.jceh.2024.101366","DOIUrl":"https://doi.org/10.1016/j.jceh.2024.101366","url":null,"abstract":"<div><h3>Background</h3><p>Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients.</p></div><div><h3>Methods</h3><p>In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed.</p></div><div><h3>Results</h3><p>Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18–70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these.</p></div><div><h3>Conclusion</h3><p>The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.</p></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067077","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}
Rejection following liver transplantation continues to impact transplant recipients although rates have decreased over time with advances in immunosuppression management. The diagnosis of rejection remains challenging with liver biopsy remaining the reference standard for diagnosis. Proper classification of rejection type and severity is imperative as this guides management and ultimately graft preservation. Future areas of promise include non-invasive testing for detection of rejection to reduce the morbidity associated with invasive testing and further advances in immunosuppression management to reduce toxicities associated with immunosuppression while minimizing rejection related morbidity.
{"title":"Rejection in Liver Transplantation Recipients","authors":"Haripriya Maddur , Nicole Wilson , Pallavi Patil , Sumeet Asrani","doi":"10.1016/j.jceh.2024.101363","DOIUrl":"https://doi.org/10.1016/j.jceh.2024.101363","url":null,"abstract":"<div><p>Rejection following liver transplantation continues to impact transplant recipients although rates have decreased over time with advances in immunosuppression management. The diagnosis of rejection remains challenging with liver biopsy remaining the reference standard for diagnosis. Proper classification of rejection type and severity is imperative as this guides management and ultimately graft preservation. Future areas of promise include non-invasive testing for detection of rejection to reduce the morbidity associated with invasive testing and further advances in immunosuppression management to reduce toxicities associated with immunosuppression while minimizing rejection related morbidity.</p></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062769","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}
Pub Date : 2024-02-20DOI: 10.1016/j.jceh.2024.101373
Bijaya K. Padhi , Aravind P. Gandhi , Mokanpally Sandeep , Muhammad A. Shamim , Arka De , Sahaj Rathi , Surender Singh , Ajay Duseja , Sunil Taneja
Background & aims
Frailty in patients with cirrhosis is associated with increased morbidity and mortality. In this study, we aimed to determine the prevalence of frailty and its impact on mortality and hospitalization in patients with cirrhosis.
Methods
An elaborate search was undertaken in the databases “PubMed, Scopus, Web of Science, and Cochrane, and preprint servers”, and an assessment of all published articles till 17 February 2023 was done. Studies that provided data on prevalence, mortality and hospitalization among frail patients with cirrhosis were included. The study characteristics and data on the prevalence, mortality, and hospitalization were extracted from included studies. The primary outcome was to estimate the pooled prevalence of frailty and determine its impact on mortality and hospitalization in patients with cirrhosis.
Results
Overall, 12 studies were included. Data on prevalence of frailty and mortality were available in 11 studies, while seven studies reported data on hospitalization. The analysis conducted among 6126 patients with cirrhosis revealed pooled prevalence of frailty to be 32% (95% confidence interval [CI], 24–41). A total of 540 events of death revealed a pooled mortality rate of 29% (95% CI, 19–41). Six-month and twelve-month pooled estimates of mortality were found to be 24% (95% CI, 17–33) and 33% (95% CI, 23–45), respectively. The pooled hospitalization rate among the seven studies was 43% (95% CI, 21–68).
Conclusion
The prevalence of frailty in patients with cirrhosis is high, leading to poor outcomes. Frailty assessment should become an integral part of cirrhosis evaluation.
{"title":"Prevalence of Frailty and Its Impact on Mortality and Hospitalization in Patients With Cirrhosis: A Systematic Review and Meta-analysis","authors":"Bijaya K. Padhi , Aravind P. Gandhi , Mokanpally Sandeep , Muhammad A. Shamim , Arka De , Sahaj Rathi , Surender Singh , Ajay Duseja , Sunil Taneja","doi":"10.1016/j.jceh.2024.101373","DOIUrl":"https://doi.org/10.1016/j.jceh.2024.101373","url":null,"abstract":"<div><h3>Background & aims</h3><p>Frailty in patients with cirrhosis is associated with increased morbidity and mortality. In this study, we aimed to determine the prevalence of frailty and its impact on mortality and hospitalization in patients with cirrhosis.</p></div><div><h3>Methods</h3><p>An elaborate search was undertaken in the databases “PubMed, Scopus, Web of Science, and Cochrane, and preprint servers”, and an assessment of all published articles till 17 February 2023 was done. Studies that provided data on prevalence, mortality and hospitalization among frail patients with cirrhosis were included. The study characteristics and data on the prevalence, mortality, and hospitalization were extracted from included studies. The primary outcome was to estimate the pooled prevalence of frailty and determine its impact on mortality and hospitalization in patients with cirrhosis.</p></div><div><h3>Results</h3><p>Overall, 12 studies were included. Data on prevalence of frailty and mortality were available in 11 studies, while seven studies reported data on hospitalization. The analysis conducted among 6126 patients with cirrhosis revealed pooled prevalence of frailty to be 32% (95% confidence interval [CI], 24–41). A total of 540 events of death revealed a pooled mortality rate of 29% (95% CI, 19–41). Six-month and twelve-month pooled estimates of mortality were found to be 24% (95% CI, 17–33) and 33% (95% CI, 23–45), respectively. The pooled hospitalization rate among the seven studies was 43% (95% CI, 21–68).</p></div><div><h3>Conclusion</h3><p>The prevalence of frailty in patients with cirrhosis is high, leading to poor outcomes. Frailty assessment should become an integral part of cirrhosis evaluation.</p></div><div><h3>Registry and registration number of study</h3><p>PROSPERO 2022 CRD42022377507.</p></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067078","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}
Pub Date : 2024-02-19DOI: 10.1016/j.jceh.2024.101371
Bale Govardhan , V. Kulkarni Anand , Padaki Nagaraja Rao , P. Balachandran Menon , Sharma Mithun , Mitnala Sasikala , T.R. Sowmya , Sekaran Anuradha , C. Pawar Smita , D. Nageshwar Reddy , Vishnubhotla Ravikanth
Background
A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role.
Methods
This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann–Whitney U/Chi-square test and odds ratio (95% confidence interval) were used.
Results
There was no significant difference (Odds ratio = 0.76; 95% CI −0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron–exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen.
Conclusion
Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.
{"title":"17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population","authors":"Bale Govardhan , V. Kulkarni Anand , Padaki Nagaraja Rao , P. Balachandran Menon , Sharma Mithun , Mitnala Sasikala , T.R. Sowmya , Sekaran Anuradha , C. Pawar Smita , D. Nageshwar Reddy , Vishnubhotla Ravikanth","doi":"10.1016/j.jceh.2024.101371","DOIUrl":"10.1016/j.jceh.2024.101371","url":null,"abstract":"<div><h3>Background</h3><p>A splice variant in <em>HSD17B13</em> gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (<em>PNPLA3</em>-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role.</p></div><div><h3>Methods</h3><p>This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); <em>HSD17B13</em>-A-INS/I148M-<em>PNPLA3</em> variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann–Whitney U/Chi-square test and odds ratio (95% confidence interval) were used.</p></div><div><h3>Results</h3><p>There was no significant difference (Odds ratio = 0.76; 95% CI −0.57 to 1.03; <em>P</em> = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; <em>P</em> = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; <em>P</em> = 0.91) between <em>HSD17B13-</em>wild and variant carriers were noted. Significantly elevated liver enzymes were seen in <em>PNPLA3</em>-148-variant/<em>HSD17B13-</em>wild compared with <em>PNPLA3</em>-148-variant/<em>HSD17B13-</em>variant (90.44 ± 59.0 vs. 112.32 ± 61.78; <em>P</em> = 0.02). No difference in steatosis (<em>P</em> = 0.51) between <em>HSD17B13</em>-wild and variant carriers was noted. No other variants in the intron–exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen.</p></div><div><h3>Conclusion</h3><p>Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of <em>PNPLA3</em> variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.</p></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965800","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}
Pub Date : 2024-02-19DOI: 10.1016/j.jceh.2024.101370
Gautam Ray
{"title":"Applicability of Risk Scores to an Indian Cohort of Hepatitis B-Related Hepatocellular Carcinoma Patients","authors":"Gautam Ray","doi":"10.1016/j.jceh.2024.101370","DOIUrl":"10.1016/j.jceh.2024.101370","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965855","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}
Pub Date : 2024-02-17DOI: 10.1016/j.jceh.2024.101362
Narendra S. Choudhary, Ajay Podisatti, Swapnil Dhampalwar, Kunwar A. Singh, Neeraj Saraf, Arvinder S. Soin
{"title":"Prevalence of Modifiable Risk Factors for de novo Malignancies After Living Donor Liver Transplantation","authors":"Narendra S. Choudhary, Ajay Podisatti, Swapnil Dhampalwar, Kunwar A. Singh, Neeraj Saraf, Arvinder S. Soin","doi":"10.1016/j.jceh.2024.101362","DOIUrl":"https://doi.org/10.1016/j.jceh.2024.101362","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052280","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}
Pub Date : 2024-02-15DOI: 10.1016/j.jceh.2024.101365
Ali Mahmoudi , Amin Jalili , Alexandra E. Butler , Seyed H. Aghaee-Bakhtiari , Tannaz Jamialahmadi , Amirhossein Sahebkar
Background
MicroRNAs (miRNAs) are promising therapeutic agents for non-alcoholic fatty liver disease (NAFLD). This study aimed to identify key genes/proteins involved in NAFLD pathogenesis and progression and to evaluate miRNAs influencing their expression.
Methods
Gene expression profiles from datasets GSE151158, GSE163211, GSE135251, GSE167523, GSE46300, and online databases were analyzed to identify significant NAFLD-related genes. Then, protein–protein interaction networks and module analysis identified hub genes/proteins, which were validated using real-time PCR in oleic acid-treated HepG2 cells. Functional enrichment analysis evaluated signaling pathways and biological processes. Gene-miRNA interaction networks identified miRNAs targeting critical NAFLD genes.
Results
The most critical overexpressed hub genes/proteins included: TNF, VEGFA, TLR4, CYP2E1, ACE, SCD, FASN, SREBF2, and TGFB1 based on PPI network analysis, of which TNF, TLR4, SCD, FASN, SREBF2, and TGFB1 were up-regulated in oleic acid-treated HepG2 cells. Functional enrichment analysis for biological processes highlighted programmed necrotic cell death, lipid metabolic process response to reactive oxygen species, and inflammation. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the highest adjusted P-value signaling pathways encompassed AGE-RAGE in diabetic complications, TNF, and HIF-1 signaling pathways. In gene-miRNA network analysis, miR-16 and miR-124 were highlighted as the miRNAs exerting the most influence on important NAFLD-related genes.
Conclusion
In silico analyses identified NAFLD therapeutic targets and miRNA candidates to guide further experimental investigation.
{"title":"Exploration of the Key Genes Involved in Non-alcoholic Fatty Liver Disease and Possible MicroRNA Therapeutic Targets","authors":"Ali Mahmoudi , Amin Jalili , Alexandra E. Butler , Seyed H. Aghaee-Bakhtiari , Tannaz Jamialahmadi , Amirhossein Sahebkar","doi":"10.1016/j.jceh.2024.101365","DOIUrl":"10.1016/j.jceh.2024.101365","url":null,"abstract":"<div><h3>Background</h3><p>MicroRNAs (miRNAs) are promising therapeutic agents for non-alcoholic fatty liver disease (NAFLD). This study aimed to identify key genes/proteins involved in NAFLD pathogenesis and progression and to evaluate miRNAs influencing their expression.</p></div><div><h3>Methods</h3><p>Gene expression profiles from datasets GSE151158, GSE163211, GSE135251, GSE167523, GSE46300, and online databases were analyzed to identify significant NAFLD-related genes. Then, protein–protein interaction networks and module analysis identified hub genes/proteins, which were validated using real-time PCR in oleic acid-treated HepG2 cells. Functional enrichment analysis evaluated signaling pathways and biological processes. Gene-miRNA interaction networks identified miRNAs targeting critical NAFLD genes.</p></div><div><h3>Results</h3><p>The most critical overexpressed hub genes/proteins included: TNF, VEGFA, TLR4, CYP2E1, ACE, SCD, FASN, SREBF2, and TGFB1 based on PPI network analysis, of which TNF, TLR4, SCD, FASN, SREBF2, and TGFB1 were up-regulated in oleic acid-treated HepG2 cells. Functional enrichment analysis for biological processes highlighted programmed necrotic cell death, lipid metabolic process response to reactive oxygen species, and inflammation. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the highest adjusted <em>P</em>-value signaling pathways encompassed AGE-RAGE in diabetic complications, TNF, and HIF-1 signaling pathways. In gene-miRNA network analysis, miR-16 and miR-124 were highlighted as the miRNAs exerting the most influence on important NAFLD-related genes.</p></div><div><h3>Conclusion</h3><p><em>In silico</em> analyses identified NAFLD therapeutic targets and miRNA candidates to guide further experimental investigation.</p></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139812453","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}
Pub Date : 2024-02-12DOI: 10.1016/j.jceh.2024.101364
Hafiz Ghufran , Maryam Azam , Azra Mehmood , Muhammad Umair , Maria T. Baig , Saba Tasneem , Hira Butt , Sheikh Riazuddin
Background/Aims
Mesenchymal stem cells (MSCs) are potential alternatives for liver fibrosis treatment; however, their optimal sources remain uncertain. This study compares the ex-vivo expansion characteristics of MSCs obtained from adipose tissue (AT) and umbilical cord (UC) and assesses their therapeutic potential for liver fibrosis treatment.
Methods
Since MSCs from early to mid-passage numbers (P2–P6) are preferable for cellular therapy, we investigated the growth kinetics of AT-MSCs and UC-MSCs up to P6 and evaluated their therapeutic effects in a rat model of liver fibrosis induced by diethylnitrosamine.
Results
Results from the expansion studies demonstrated that both cell types exhibited bona fide characteristics of MSCs, including surface antigens, pluripotent gene expression, and differentiation potential. However, AT-MSCs demonstrated a shorter doubling time (58.2 ± 7.3 vs. 82.3 ± 4.3 h; P < 0.01) and a higher population doubling level (10.1 ± 0.7 vs. 8.2 ± 0.3; P < 0.01) compared to UC-MSCs, resulting in more cellular yield (230 ± 9.0 vs. 175 ± 13.2 million) in less time. Animal studies demonstrated that both MSC types significantly reduced liver fibrosis (P < 0.05 vs. the control group) while also improving liver function and downregulating fibrosis-associated gene expression.
Conclusion
AT-MSCs and UC-MSCs effectively reduce liver fibrosis. However, adipose cultures display an advantage by yielding a higher number of MSCs in a shorter duration, rendering them a viable choice for scenarios requiring immediate single-dose administration, often encountered in clinical settings.
{"title":"Adipose Tissue and Umbilical Cord Tissue: Potential Sources of Mesenchymal Stem Cells for Liver Fibrosis Treatment","authors":"Hafiz Ghufran , Maryam Azam , Azra Mehmood , Muhammad Umair , Maria T. Baig , Saba Tasneem , Hira Butt , Sheikh Riazuddin","doi":"10.1016/j.jceh.2024.101364","DOIUrl":"10.1016/j.jceh.2024.101364","url":null,"abstract":"<div><h3>Background/Aims</h3><p>Mesenchymal stem cells (MSCs) are potential alternatives for liver fibrosis treatment; however, their optimal sources remain uncertain. This study compares the ex-vivo expansion characteristics of MSCs obtained from adipose tissue (AT) and umbilical cord (UC) and assesses their therapeutic potential for liver fibrosis treatment.</p></div><div><h3>Methods</h3><p>Since MSCs from early to mid-passage numbers (P2–P6) are preferable for cellular therapy, we investigated the growth kinetics of AT-MSCs and UC-MSCs up to P6 and evaluated their therapeutic effects in a rat model of liver fibrosis induced by diethylnitrosamine.</p></div><div><h3>Results</h3><p>Results from the expansion studies demonstrated that both cell types exhibited bona fide characteristics of MSCs, including surface antigens, pluripotent gene expression, and differentiation potential. However, AT-MSCs demonstrated a shorter doubling time (58.2 ± 7.3 vs. 82.3 ± 4.3 h; <em>P</em> < 0.01) and a higher population doubling level (10.1 ± 0.7 vs. 8.2 ± 0.3; <em>P</em> < 0.01) compared to UC-MSCs, resulting in more cellular yield (230 ± 9.0 vs. 175 ± 13.2 million) in less time. Animal studies demonstrated that both MSC types significantly reduced liver fibrosis (<em>P</em> < 0.05 vs. the control group) while also improving liver function and downregulating fibrosis-associated gene expression.</p></div><div><h3>Conclusion</h3><p>AT-MSCs and UC-MSCs effectively reduce liver fibrosis. However, adipose cultures display an advantage by yielding a higher number of MSCs in a shorter duration, rendering them a viable choice for scenarios requiring immediate single-dose administration, often encountered in clinical settings.</p></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139832808","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}