Wolters Leonieke M M, Hansen Bettina E, Niesters Hubert G M, DeHertogh Deborah, de Man Robert A
Department of Gastroenterology & Hepatology, University Hospital Rotterdam, Rotterdam, The Netherlands.
J Hepatol. 2002 Jul;37(1):137-44. doi: 10.1016/s0168-8278(02)00115-0.
BACKGROUND/AIMS: Nucleoside analogues inhibit hepatitis B virus (HBV) replication. Entecavir, a new guanine nucleoside, has also been shown to reduce covalently closed circular DNA (cccDNA) to undetectable levels in woodchucks chronically infected with hepatitis virus. Mathematical description of changes in viral load during and after therapy may help to understand the several events that take place during nucleoside analogue treatment.
Ten chronic hepatitis B patients were evaluated with a mathematical model during and after withdrawal of four doses of entecavir. Blood was drawn for HBV DNA measurement at frequent intervals. Non-linear modelling was used to fit individual patient data.
The median effectiveness in blocking viral production is 96% (n=10, range 87-98%). The median half-life of viral turn-over was 16 h (range 12-29 h). The median half-life of infected hepatocytes was 257 h (=10.7 days) (n=9, range 112-762 h). Rebound of viral replication also followed a bi-phasic return to baseline levels.
Decay and rebound of viral concentration during and after entecavir therapy, respectively, showed a bi-phasic pattern. Both can be described with a mathematical model. Data on levels of cccDNA in the liver in these patients could be helpful in supporting the parameters as calculated with the model.
背景/目的：核苷类似物可抑制乙型肝炎病毒（HBV）复制。恩替卡韦，一种新型鸟嘌呤核苷，已被证明可使慢性感染肝炎病毒的土拨鼠体内共价闭合环状DNA（cccDNA）降至检测不到的水平。对治疗期间及之后病毒载量变化进行数学描述，可能有助于理解核苷类似物治疗期间发生的一系列事件。
在给予四剂恩替卡韦期间及停药后，使用数学模型对10例慢性乙型肝炎患者进行评估。频繁采集血液以检测HBV DNA。采用非线性建模拟合个体患者数据。
阻断病毒产生的中位有效性为96%（n = 10，范围87 - 至98%）。病毒周转的中位半衰期为16小时（范围12 - 至29小时）。受感染肝细胞的中位半衰期为257小时（= 10.7天）（n = 9，范围112 - 至762小时）。病毒复制的反弹也呈双相恢复至基线水平。
恩替卡韦治疗期间及之后病毒浓度的衰减和反弹分别呈现双相模式。两者均可用数学模型描述。这些患者肝脏中cccDNA水平的数据可能有助于支持用该模型计算出的参数。
