2018-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647696摘要：慢性B 型肝炎病毒(HBV)感染時間常在嬰幼期。若要發展兒童早期有效清除HBV 藥物，必須對於兒童宿主與HBV 交互作用有更多了解。B 肝核心抗體(anti-HBc)濃度是測量宿主對HBV免疫反應的非侵犯性標記;牛磺膽酸鈉共轉運多肽(NTCP)是新發現的HBV 感染肝細胞之接受器，然上述此二者與兒童HBV 感染預後之關係仍缺乏資料，值得研究。本計畫擬探討(1)長程追蹤之HBV 帶原兒童早期HBV e 抗原抗體轉換之特徵;(2)anti-HBc 濃度變化可否作為預測HBV 感染自然史標記;(3)兒童NTCP 基因變異對HBV e 與S 抗原雙陽性母親嬰兒預防注射失敗及自然史之影響。450 名長程追蹤之慢性HBV 帶原兒童，及另100 名HBV e 及S 抗原雙陽性母親之嬰兒將進入本研究。本計畫第一年將研究HBV 帶原兒童<=5，6-10，11-20，及>20 歲時血中anti-HBc濃度與性別，HBV 預防注射史，母親HBV 肝標記，最高ALT 值，HBV e 抗原抗體轉換年齡， HBV S抗原濃度，及S 抗原清除年齡等之關聯。第二年將分析兒童NTCP 基因序列變異是否影響e 及S抗原雙陽性母親嬰兒預防注射成敗。第三年將探討兒童NTCP 基因變異對慢性HBV 感染病程之影響，及其在肝組織之表現與肝細胞HBV S 及核心抗原表現及預後的關係。本研究成果將增進對影響HBV 慢性感染由兒童與成人之自然病程，及HBV e 與S 抗原雙陽母親嬰兒預防注射失敗原因的了解。<br> Abstract: Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and liver cancer. Itmainly starts in infancy and early childhood. Children with chronic HBV infection are considered to be in animmune tolerance status to HBV. Occasionally children may overcome immune tolerance, entering theinflammatory phase with hepatitis B e antigen (HBeAg) seroconversion very early. To develop effectivetherapy for early elimination of HBV, understanding the host factor and immune response to HBV in earlychildhood is needed.Antibody to hepatitis B core antigen (anti-HBc) is a noninvasive seromarker for host immune responseto HBV, thus is suitable for use in children. Furthermore, sodium-taurocholate co-transporting polypeptide(NTCP) is a newly recognized HBV hepatocyte cell receptor, and was related to the outcome of HBVinfection in adults. Chronic HBV infection often starts in infancy and early childhood, but the related data arelacking.Specific aims of this project are to study : (1) the age at HBeAg seroconversion in chronic HBVinfected children during long-term follow-up, and factors facilitating the early and very early HBeAgseroconversion; (2) the significance of sequential anti-HBc titers in the natural course of chronic HBVinfection from infancy to adulthood; (3) the role of host NTCP on HBV vaccine failure in infants of HBeAgpositive hepatitis B surface antigen (HBsAg) carrier mothers, and in the long-term natural history of chronicHBV infection.Totally 450 children with chronic HBV infection, long-term followed every 6 months (first cohort), andanother 100 infants of HBeAg and HBsAg positive mothers (second cohort) will be studied. During the 1styear of the project, factors facilitating early HBeAg seroconversion will be studied. Serial anti-HBcquantitation will be performed for children at <=5, 6-10, 11-20, and >20 years old during follow-up.Anti-HBc titers will be correlated with gender, HBV vaccination history, maternal HBV status, peak ALTlevels, age at HBeAg seroconversion, serial HBsAg titers, and age at HBsAg seroclearance.During the 2nd year, NTCP genetic sequences and its variants will be studied in 100 infants of HBsAgand HBeAg positive mothers. The role of NTCP genetic variants on the follow-up outcome of HBVimmunization (vaccine failure or not) will be analyzed in those infants.During the 3rd year, the effect of NTCP genetic variation on the clinical course, including age atHBeAg seroconversion, severity of acute exacerbation, age at HBsAg clearance, and complication(s) will beanalyzed in children with chronic HBV infection. Correlation will be made between the protein expressionpatterns of NTCP and HBsAg/HBcAg expression, and also the clinical course and outcome of chronic HBVinfection.The results of our study will enhance the understanding on the host-virus interaction in chronic HBVinfection starting from perinatal transmission to adulthood. Hopefully it will be helpful to clarify, at least inpart, the mechanisms of vaccine failure and the natural history of chronic HBV infection.LovastatinVildagliptinExosomeAnaplastic thyroid cancerproteomicscellular differentiationOxythiamineTransketolase