Pub Date : 2024-10-01Epub Date: 2024-05-14DOI: 10.3350/cmh.2024.0348
Joseph C Ahn, Ju Dong Yang
{"title":"Unveiling etiology-specific blood biomarkers in hepatocellular carcinoma: A gateway to personalized medicine: Editorial on \"Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma\".","authors":"Joseph C Ahn, Ju Dong Yang","doi":"10.3350/cmh.2024.0348","DOIUrl":"10.3350/cmh.2024.0348","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-05-29DOI: 10.3350/cmh.2024.0058
Xueshuai Wan, Karin Wisskirchen, Tao Jin, Lu Yang, Xiaorui Wang, Xiang'an Wu, Fang Liu, Yu Wu, Christy Ma, Yong Pang, Qi Li, Ke Zhang, Ulrike Protzer, Shunda Du
Background/aims: Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).
Methods: Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results: SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood.
Conclusion: SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
{"title":"Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting.","authors":"Xueshuai Wan, Karin Wisskirchen, Tao Jin, Lu Yang, Xiaorui Wang, Xiang'an Wu, Fang Liu, Yu Wu, Christy Ma, Yong Pang, Qi Li, Ke Zhang, Ulrike Protzer, Shunda Du","doi":"10.3350/cmh.2024.0058","DOIUrl":"10.3350/cmh.2024.0058","url":null,"abstract":"<p><strong>Background/aims: </strong>Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).</p><p><strong>Methods: </strong>Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.</p><p><strong>Results: </strong>SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood.</p><p><strong>Conclusion: </strong>SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-01DOI: 10.3350/cmh.2024.0482
Abdelrahman M Attia, Hasmik Adetyan, Ju Dong Yang
{"title":"Severity of microvascular invasion does matter in hepatocellular carcinoma prognosis: Editorial on \"Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging\".","authors":"Abdelrahman M Attia, Hasmik Adetyan, Ju Dong Yang","doi":"10.3350/cmh.2024.0482","DOIUrl":"10.3350/cmh.2024.0482","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-03DOI: 10.3350/cmh.2024.0465
Cho-Rong Lee, Sung-Gyoo Park
{"title":"Class II transactivator restricts viral replication, extending its effect to HBV: Editorial on \"Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction\".","authors":"Cho-Rong Lee, Sung-Gyoo Park","doi":"10.3350/cmh.2024.0465","DOIUrl":"10.3350/cmh.2024.0465","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-08DOI: 10.3350/cmh.2024.0499
Beom Kyung Kim
{"title":"Decreasing performance of HCC prediction models during antiviral therapy for hepatitis B: what else to keep in mind: Editorial on \"Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients\".","authors":"Beom Kyung Kim","doi":"10.3350/cmh.2024.0499","DOIUrl":"10.3350/cmh.2024.0499","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-19DOI: 10.3350/cmh.2024.0252
Gi-Ae Kim, Seung Won Choi, Seungbong Han, Young-Suk Lim
Background/aims: Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are significantly associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. Nonetheless, the relationship between HBV DNA levels and liver fibrosis scores is unclear.
Methods: A historical cohort comprising 6,949 non-cirrhotic Korean CHB patients without significant alanine aminotransferase elevation was investigated. The association of HBV DNA levels with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (FIB)-4 score at baseline was analyzed using general linear models.
Results: In HBeAg-negative patients (n=4,868), HBV DNA levels correlated linearly with both APRI and FIB-4 scores. In contrast, in HBeAg-positive patients (n=2,081), HBV DNA levels correlated inversely with both APRI and FIB-4 scores. Across the entire cohort, a significant non-linear parabolic relationship was identified between HBV DNA levels and fibrosis scores, independent of age and other covariates. Notably, moderate viral loads (6-7 log10 IU/mL) corresponded to the highest APRI and FIB-4 scores (p<0.001). Over a median 10-year follow-up, 435 patients (6.3%) developed HCC. Higher APRI scores ≥0.5 and FIB-4 scores ≥1.45 were significantly associated with elevated HCC risk (p<0.001 for both). HBV DNA level remained a significant predictive factor for HCC development, even after adjusting for APRI or FIB-4 scores.
Conclusion: HBV viral load is significantly correlated with APRI and FIB-4 scores, and is also associated with HCC risk independent of those scores in CHB patients. These findings suggest that HBV DNA level is associated with hepatocarcinogenesis through both direct and indirect pathways.
背景/目的:血清乙型肝炎病毒(HBV)DNA水平和非侵入性肝纤维化评分与慢性乙型肝炎(CHB)患者的肝细胞癌(HCC)风险显著相关。然而,HBV DNA水平与肝纤维化评分之间的关系尚不清楚:方法:调查了由 6,949 名无肝硬化、丙氨酸氨基转移酶无明显升高的韩国慢性乙型肝炎患者组成的历史队列。采用一般线性模型分析了基线时 HBV DNA 水平与天冬氨酸氨基转移酶与血小板比值指数(APRI)和纤维化(FIB)-4 评分的关系:结果:在 HBeAg 阴性患者(4 868 人)中,HBV DNA 水平与 APRI 和 FIB-4 评分呈线性相关。相比之下,在 HBeAg 阳性患者(人数=2,081)中,HBV DNA 水平与 APRI 和 FIB-4 评分成反比。在整个队列中,HBV DNA 水平与纤维化评分之间存在显著的非线性抛物线关系,不受年龄和其他协变量的影响。值得注意的是,中等病毒载量(6-7 log10 IU/mL)与最高的 APRI 和 FIB-4 评分相对应(PConclusions:HBV病毒载量与APRI和FIB-4评分有明显相关性,而且与HCC风险相关,与CHB患者的这些评分无关。这些研究结果表明,HBV DNA水平通过直接和间接途径与肝癌发生相关。
{"title":"Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B.","authors":"Gi-Ae Kim, Seung Won Choi, Seungbong Han, Young-Suk Lim","doi":"10.3350/cmh.2024.0252","DOIUrl":"10.3350/cmh.2024.0252","url":null,"abstract":"<p><strong>Background/aims: </strong>Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are significantly associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. Nonetheless, the relationship between HBV DNA levels and liver fibrosis scores is unclear.</p><p><strong>Methods: </strong>A historical cohort comprising 6,949 non-cirrhotic Korean CHB patients without significant alanine aminotransferase elevation was investigated. The association of HBV DNA levels with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (FIB)-4 score at baseline was analyzed using general linear models.</p><p><strong>Results: </strong>In HBeAg-negative patients (n=4,868), HBV DNA levels correlated linearly with both APRI and FIB-4 scores. In contrast, in HBeAg-positive patients (n=2,081), HBV DNA levels correlated inversely with both APRI and FIB-4 scores. Across the entire cohort, a significant non-linear parabolic relationship was identified between HBV DNA levels and fibrosis scores, independent of age and other covariates. Notably, moderate viral loads (6-7 log10 IU/mL) corresponded to the highest APRI and FIB-4 scores (p<0.001). Over a median 10-year follow-up, 435 patients (6.3%) developed HCC. Higher APRI scores ≥0.5 and FIB-4 scores ≥1.45 were significantly associated with elevated HCC risk (p<0.001 for both). HBV DNA level remained a significant predictive factor for HCC development, even after adjusting for APRI or FIB-4 scores.</p><p><strong>Conclusion: </strong>HBV viral load is significantly correlated with APRI and FIB-4 scores, and is also associated with HCC risk independent of those scores in CHB patients. These findings suggest that HBV DNA level is associated with hepatocarcinogenesis through both direct and indirect pathways.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-23DOI: 10.3350/cmh.2024.0552
Xiaoqian Xu, Hong You, Jidong Jia, Yuanyuan Kong
{"title":"Correspondence to editorial on \"Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients\".","authors":"Xiaoqian Xu, Hong You, Jidong Jia, Yuanyuan Kong","doi":"10.3350/cmh.2024.0552","DOIUrl":"10.3350/cmh.2024.0552","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-05-07DOI: 10.3350/cmh.2024.0327
Junlong Dai, Jimmy Che-To Lai, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip
{"title":"Unlocking the future: Machine learning sheds light on prognostication for early-stage hepatocellular carcinoma: Editorial on \"Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma\".","authors":"Junlong Dai, Jimmy Che-To Lai, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip","doi":"10.3350/cmh.2024.0327","DOIUrl":"10.3350/cmh.2024.0327","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-05-10DOI: 10.3350/cmh.2024.0343
Yasuko Iwakiri
{"title":"Unlocking the role of liver sinusoidal endothelial cells: Key players in liver fibrosis: Editorial on \"Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis\".","authors":"Yasuko Iwakiri","doi":"10.3350/cmh.2024.0343","DOIUrl":"10.3350/cmh.2024.0343","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}