Zahm F E, Bonino F, Giuseppetti R, Rapicetta M
F. Hoffman La Roche Ltd., Basel, Switzerland.
Ital J Gastroenterol Hepatol. 1998 Oct;30(5):510-6.
BACKGROUND & AIMS: Ganciclovir is a nucleoside analogue active against cytomegalovirus. The compound has also shown in vitro and in vivo activity against duck hepatitis B virus. We investigated the ability of ganciclovir to inhibit another Hepadnaviridae, the woodchuck hepatitis virus, which is the most closely related with hepatitis B virus. We compared two different quantification methods of woodchuck hepatitis virus DNA.
We treated seven chronic woodchuck hepatitis virus carriers by daily intravenous injections of 5 mg/kg body weight of ganciclovir for seven consecutive days, and followed the animals for 3 weeks post therapy. In addition to traditional X-ray autoradiography, which is a semi-quantitative method, we evaluated woodchuck hepatitis virus DNA levels with storage phosphor technology.
A reduction in serum woodchuck hepatitis virus DNA was observed during treatment in all animals regardless of pre-treatment viraemia levels when using x-ray films and phosphor storage technology. The latter method allowed calculation of mean values of average phosphor imager signals. When comparing the mean values (+/- 95% confidence intervals) before and during therapy, a significant decrease in woodchuck hepatitis virus DNA (80 to 100%) could be shown. After stopping therapy, virus DNA rebounded in all animals.
Our results show that ganciclovir inhibits viral replication in woodchucks chronically infected with woodchuck hepatitis virus. No signs of toxicity were observed. After dot-blot hybridization, storage phosphor imaging was proven superior to X-ray autoradiography for measuring viral DNA. Storage phosphor technology is highly sensitive, quantitative and easy to handle. By comparing mean values and confidence intervals before and during therapy, treatment effects can be distinguished from natural fluctuations.
更昔洛韦是一种对巨细胞病毒有活性的核苷类似物。该化合物在体外和体内对鸭乙型肝炎病毒也显示出活性。我们研究了更昔洛韦抑制另一种嗜肝DNA病毒科——土拨鼠肝炎病毒（woodchuck hepatitis virus）的能力，该病毒与乙型肝炎病毒关系最为密切。我们比较了两种不同的土拨鼠肝炎病毒DNA定量方法。
我们对7只慢性土拨鼠肝炎病毒携带者连续7天每天静脉注射5mg/kg体重的更昔洛韦，并在治疗后3周对动物进行随访。除了传统的X射线放射自显影（一种半定量方法）外，我们还使用存储磷光技术评估土拨鼠肝炎病毒DNA水平。
使用X射线胶片和磷光存储技术时，无论治疗前病毒血症水平如何，所有动物在治疗期间血清土拨鼠肝炎病毒DNA均有下降。后一种方法允许计算平均磷光成像仪信号的平均值。比较治疗前和治疗期间的平均值（±95%置信区间），可显示出土拨鼠肝炎病毒DNA有显著下降（80%至100%）。停止治疗后，所有动物的病毒DNA均反弹。
我们的结果表明，更昔洛韦可抑制慢性感染土拨鼠肝炎病毒的土拨鼠体内的病毒复制。未观察到毒性迹象。在斑点杂交后，证明存储磷光成像在测量病毒DNA方面优于X射线放射自显影。存储磷光技术高度灵敏、定量且易于操作。通过比较治疗前和治疗期间的平均值和置信区间，可将治疗效果与自然波动区分开来。
