兒童慢性B型肝炎病毒感染自然病程影響因子之長程研究：病毒量及病毒全長基因變化之探討(1/3)

Abstract

目的/背景：在B 型肝炎病毒慢性感染之自然史中，急性肝功能惡化可能造成進行性肝傷害， 甚至肝衰竭。長程前瞻性研究以探討B 肝病毒量在急性肝功能惡化之及後，e 抗原抗體轉變 是否具帶動角色，是很重要的，可惜這方面的研究極欠缺，尤其在兒童及年輕成人方面。 對象及方法：我們長程追蹤了460 名慢性B 型肝炎病毒的兒童。每半年檢驗一次肝功能及血 B 肝標記。其中72 名最初年齡小於15 歲，追蹤期間大於10 年，而且未曾接受過治療者進入 本研究。共有59 人在追蹤過程中發生e 抗原抗體轉變，另13 人則一直保持e 抗原陽性。在 病人肝功能變化前後我們測量其血清病毒濃度，然後並與其性別年齡，基因型等作相關分析。 結果：發現B 型肝炎濃度變化主要有三種型式：(一)在肝功能上升前，病毒濃度保持高水平， 經過一到數次的肝功能變化之後，病毒濃度便急速下降(>102 copies/ml ) (n=62) (二)在肝功能 上揚之前，病毒濃度也上升(n=5)。(三)在肝功能上揚之前，病毒濃度先下降(n=4)。另外有一 人無法歸類。在 e 抗原陰轉之前的病毒濃度明顯高於陰轉之後。在陰轉之前，肝功能上升下 降起伏變化的次數明顯等於陰轉之後，但是B 型肝炎病毒濃度的上下起伏次數在陰轉前後都 並無改變。 結論：大多數B 型肝炎帶原的兒童及青少年，他們身上的病毒濃度在e 抗原陰轉之後才會真 正下降。在陰轉之前，肝功能上下起伏是常見，但不見得伴有B 型肝炎病毒濃度的上下起伏。 所以病毒濃度並非啟動e 抗原陰轉的主因，應另外思考其他因素，例如宿主與病毒間的免疫 反應。

Aim/Background: In the natural history of chronic hepatitis B virus (HBV) infection, the acute exacerbation or alanine aminotransferase (ALT) flare-up episodes can lead to progression of liver damage, and even liver failure. Long term prospective study to explore the role of HBV viral load in the exact mechanism of acute exacerbation and its subsequent hepatitis B e antigen (HBeAg) seroconversion is very important but lacking particularly in children and young adults. Subjects and Methods: Totally 460 children with chronic HBV infection were long-term followed up for liver function profiles and HBV serum markers every 6 months. We recruited 72 children who were enrolled at the age <15 years, followed-up for more than 10 years, and without treatment. Fifty-nine of them were tepatitis B e antigen (HBeAg) seroconverted during follow-up, while 13 remained HBeAg sero-positive. We measured serum HBV DNA levels by real time PCR before, at, and after ALT flare-up was detected. Then we correlated viral levels with subsequent HBeAg seroconversion, gender, age, genotype, and histological findings. Results: The temporal profiles of HBV DNA, ALT, and HBeAg seroconversion can be divided into three major patterns among these 72 patients: (1) Plateau of HBV DNA before ALT flare-up (>2x UNL) and decreasing viral load (>102 copies/ml) (n=62). After one or several episodes of ALT flare-up, the viral load started to decrease sharply. (2) Increased viral load (>102 copies/ml) before ALT flare-up (n=5). (3) Decreased viral load (>102 copies/ml) before ALT flare-up (n=4). One patient was unclassified. The mean HBV DNA titer was much higher in the pre-HBeAg seroconversion phase than that in the 3 post-HBeAg seroconversion phase. While those of ALT flare-up are higher in the pre- HBeAg seroconversion phase, the frequencies of HBV DNA fluctuations are not different between those two phases. Conclusion: HBV viral load would not decline until they finally underwent HBeAg seroconversion in the majority of HBV carrier children and young adults. Several episodes of ALT flare-up were common in the natural course, yet they were not commonly accompanied by a surge of HBV DNA level. Most Factor(s) other than the surge of viral load may plays the key role in the initiation process of HBeAg seroconversion.