{"title":"CTLA-4 单倍型可预测慢性 HBV 感染儿童的 HBsAg 和 HBcrAg 水平以及 HBeAg 血清转换年龄","authors":"Jia-Feng Wu , Chi-San Tai , Kai-Chi Chang , Ting-Wei Chen , Huey-Ling Chen , Yen-Hsuan Ni , Hong-Yuan Hsu , Mei-Hwei Chang","doi":"10.1016/j.jhepr.2024.101061","DOIUrl":null,"url":null,"abstract":"<div><h3>Background & Aim</h3><p>Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between <em>CTLA-4</em> genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection.</p></div><div><h3>Methods</h3><p>We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the <em>CTLA-4</em> gene single nucleotide polymorphisms rs4553808 (–A1661G)/rs5742909 (–C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort.</p></div><div><h3>Results</h3><p><em>CTLA-4</em> promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the <em>CTLA-4</em> AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; <em>p</em> = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 <em>vs.</em> 0.03 log<sub>10</sub> IU/ml/year, <em>p</em> = 0.02). The <em>CTLA-4</em> AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (<em>p</em> = 0.01).</p></div><div><h3>Conclusions</h3><p>Chronic HBV-infected patients with a <em>CTLA-4</em> AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion.</p></div><div><h3>Impact and implications</h3><p>The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that <em>CTLA-4</em> haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000624/pdfft?md5=e9342693fd6a0ee89670eb57871848b4&pid=1-s2.0-S2589555924000624-main.pdf","citationCount":"0","resultStr":"{\"title\":\"CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection\",\"authors\":\"Jia-Feng Wu , Chi-San Tai , Kai-Chi Chang , Ting-Wei Chen , Huey-Ling Chen , Yen-Hsuan Ni , Hong-Yuan Hsu , Mei-Hwei Chang\",\"doi\":\"10.1016/j.jhepr.2024.101061\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background & Aim</h3><p>Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between <em>CTLA-4</em> genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection.</p></div><div><h3>Methods</h3><p>We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the <em>CTLA-4</em> gene single nucleotide polymorphisms rs4553808 (–A1661G)/rs5742909 (–C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort.</p></div><div><h3>Results</h3><p><em>CTLA-4</em> promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the <em>CTLA-4</em> AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; <em>p</em> = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 <em>vs.</em> 0.03 log<sub>10</sub> IU/ml/year, <em>p</em> = 0.02). The <em>CTLA-4</em> AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (<em>p</em> = 0.01).</p></div><div><h3>Conclusions</h3><p>Chronic HBV-infected patients with a <em>CTLA-4</em> AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion.</p></div><div><h3>Impact and implications</h3><p>The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that <em>CTLA-4</em> haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.</p></div>\",\"PeriodicalId\":14764,\"journal\":{\"name\":\"JHEP Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.5000,\"publicationDate\":\"2024-03-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2589555924000624/pdfft?md5=e9342693fd6a0ee89670eb57871848b4&pid=1-s2.0-S2589555924000624-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JHEP Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2589555924000624\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JHEP Reports","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589555924000624","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection
Background & Aim
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection.
Methods
We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (–A1661G)/rs5742909 (–C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort.
Results
CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01).
Conclusions
Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion.
Impact and implications
The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.
期刊介绍：
JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology.
The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies.
In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.
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