Basic HepatologyPub Date : 2022-09-01DOI: 10.1136/gutjnl-2022-iddf.21
K. Sun, Jie Zhao, Edmund Anthony Severn Nelson, L. Hui
{"title":"IDDF2022-ABS-0106 Iron status and non-alcoholic fatty liver disease: a mendelian randomization study","authors":"K. Sun, Jie Zhao, Edmund Anthony Severn Nelson, L. Hui","doi":"10.1136/gutjnl-2022-iddf.21","DOIUrl":"https://doi.org/10.1136/gutjnl-2022-iddf.21","url":null,"abstract":"","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114784776","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}
Basic HepatologyPub Date : 2022-09-01DOI: 10.1136/gutjnl-2022-iddf.18
John Mark Torres
{"title":"IDDF2022-ABS-0047 Prevalence and associated risk factors of hepatitis B infection among healthcare workers at a tertiary public hospital in the philippines","authors":"John Mark Torres","doi":"10.1136/gutjnl-2022-iddf.18","DOIUrl":"https://doi.org/10.1136/gutjnl-2022-iddf.18","url":null,"abstract":"","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130641943","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}
Basic HepatologyPub Date : 2021-09-01DOI: 10.1136/gutjnl-2021-iddf.9
Xiaoyu Liu, Jingying Zhou, Man Liu, Ying Wang, Mengying Hu, Rihe Liu, Leaf Huang, Hanzhuang Liu, Alfred Sze Lok Cheng
{"title":"IDDF2021-ABS-0185 Overcome primary resistance to immune checkpoint blockade in hepatocellular carcinoma","authors":"Xiaoyu Liu, Jingying Zhou, Man Liu, Ying Wang, Mengying Hu, Rihe Liu, Leaf Huang, Hanzhuang Liu, Alfred Sze Lok Cheng","doi":"10.1136/gutjnl-2021-iddf.9","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.9","url":null,"abstract":"Background Although immune checkpoint blockade (ICB) such as anti-programmed cell death 1 or its ligand (anti-PD-1/PD-L1) has revolutionized the treatment paradigm for cancer patients, most hepatocellular carcinoma (HCC) patients did not show benefits in the clinical scenario. The aim of this study is to investigate the underlying mechanisms of immunotherapy resistance in HCC and explore therapeutic approaches for enhancing HCC immunotherapy. Methods Fibrosis-associated HCC mouse model was established by chemical induction and tumor inoculation. Non-alcoholic fatty liver disease (NAFLD)-associated HCC was established by high-fat high carbohydrate diet and tumor implantation. Integrated analysis of single-cell RNA sequencing and bulk RNA sequencing were applied to identify monocytic myeloid-derived suppressor cells (M-MDSC) signature genes. Immune profiles were determined by flow cytometry. Results We found M-MDSC was specifically enriched in non-responders and a protein phosphatase was identified as a novel signature gene in M-MDSC. Inhibition of this protein phosphatase suppressed M-MDSC expansion and reduced reactive oxygen species generation, which holds promise in ameliorating the immunosuppressive microenvironment for tumor eradication. To further improve HCC therapy in ICB manner, we found an elegant nanoparticle-parceled PD-L1 trap which was superior to the conventional antibody-mediated ICB therapy. This PD-L1 trap was more up taken by the fibrotic liver environment compared to the normal liver indicating it would be suitable for majority of HCC patients. Ultimately, the PD-L1 trap triggered robust anti-tumor response in both fibrotic HCC and NAFLD-associated HCC. Mechanistically, PD-L1 trap exerted potent immune-editing function by diminishing immunosuppressive cells and boosting CD8+ T cells infiltration to the tumor. Those tumor-infiltrating CD8+ T cells were more cytotoxic with augmented cytokines production. More importantly, improved survival was observed in PD-L1 trap-treated HCC. Conclusions We uncovered a novel target for immunosuppressive myeloid cells which was closely associated with immunotherapy resistance in HCC. Moreover, a novel ICB approach showed translational potential for treating HCC with the enhanced therapeutic effect but reduced toxicity. We anticipate providing more efficacious options for HCC patients with long-term benefits. Acknowledgements: This study is supported by HMRF (16170451, 07180556) and Li Ka Shing Foundation.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121091963","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":"IDDF2021-ABS-0177 RNF135 promoter methylation is associated with immune infiltration and prognosis in hepatocellular carcinoma","authors":"Gui-jun Zhao, Xiong Liang, Yu-Ru Bai, Hao Li, Guang Yong, Yusha Liu, Yukun Liang, Xiao Wang","doi":"10.1136/gutjnl-2021-iddf.8","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.8","url":null,"abstract":"Background RING finger protein 135 (RNF135) has an important role in the occurrence of many cancers, however, the regulation and function of RNF135 in hepatocellular carcinoma (HCC) remains unknown. Methods The promoter methylation status and mRNA expression of RNF135 were evaluated by methylation-specific PCR and real-time PCR in HCC cell lines and tissues, and further analyzed from The Cancer Genome Atlas database. Transwell migration, wound healing assay, cell viability, and colony formation assay were performed to investigate the function of RNF135. GSEA analysis, TIMER database and ESTIMATE algorithm were used to decipher the associated pathway and immune infiltration. The survival analysis was applied to assess the prognostic value of RNF135. Results RNF135 expression was downregulated in 5 of 8 HCC cell lines and HCC tissues, and was negatively correlated with its promoter hypermethylation. Demethylating regent decitabine restored RNF135 expression on the cellular level. Knockdown of RNF135 expression enhanced the migration of HCC cells, while RNF135 overexpression repressed cell migration. Bioinformatics analysis revealed a positive relationship between RNF135 expression and six immune cell infiltrates (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells). Survival analysis disclosed that RNF135 hypermethylation is independently associated with poor clinical outcomes in HCC. Conclusions Decreased RNF135 expression driven by promoter hypermethylation is frequently occurred in HCC and associated with prognosis of HCC. RNF135 functions as a tumor suppressor and involves in tumor immune microenvironment in HCC.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"177 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131720887","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":"IDDF2021-ABS-0073 Characteristics of biliary microbes in patients with recurrent choledocholithiasis","authors":"Wen-hui Tan, Ruiyan Chen, Jianchuan Wu, Fang Wang, Biao Liang","doi":"10.1136/gutjnl-2021-iddf.16","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.16","url":null,"abstract":"Background To observe the characteristics of biliary tract microorganisms in patients with recurrent choledocholithiasis, and to analyze the influence of biliary tract microorganisms on the recurrence of choledocholithiasis. Methods The of tract","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132570424","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}