Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
J Hepatol. 2012 Jan;56(1):115-22. doi: 10.1016/j.jhep.2011.06.016. Epub 2011 Jul 14.
BACKGROUND & AIMS: Chronic HDV infection is an inflammatory liver disease and liver transplantation (LTX) remains the only curative treatment option for most patients. The hepatitis D virus (HDV) uses HBsAg as its surface protein, however, it is controversial to what extend HDV may be detected independently of HBsAg in blood and liver after LTX. The aims of this study were to investigate kinetics of HDV RNA and HBsAg early after LTX, to apply the data to a mathematical model and to study long-term persistence of HDV after LTX.
We retrospectively analyzed 26 patients with chronic hepatitis delta who underwent LTX between 1994 and 2009. Blood samples were obtained every 1-3 days during the first 14 days after LTX. Data were applied to a mathematical model to study viral kinetics. Available liver biopsy samples were stained for HBV and HDV viral antigens and tested for HBV DNA/cccDNA.
HBsAg and HDV RNA became negative after a median of 5 days (range 1-13) and 4 days (range 1-10), respectively. Early HDV RNA and HBsAg decline paralleled almost exactly in all patients; however the mathematical model showed a high variability of virion death. HDAg stained positive in transplanted livers in six patients in the absence of liver HBV DNA/cccDNA, serum-HBsAg, and HDV RNA for up to 19 months after LTX.
HDV RNA and HBsAg decline follow almost identical kinetic patterns within the first days after LTX. Nevertheless, intrahepatic latency of HDAg has to be considered when exploring novel concepts to withdraw HBIG.
慢性 HDV 感染是一种炎症性肝病，肝移植（LTX）仍然是大多数患者的唯一治愈治疗选择。乙型肝炎病毒（HBV）使用 HBsAg 作为其表面蛋白，然而，HBV 抗原在 LTX 后血液和肝脏中是否可以独立于 HBsAg 检测到，这存在争议。本研究的目的是研究 LTX 后早期 HDV RNA 和 HBsAg 的动力学，将数据应用于数学模型，并研究 LTX 后 HDV 的长期持续存在。
我们回顾性分析了 1994 年至 2009 年间接受 LTX 的 26 例慢性乙型肝炎 delta 患者。LTX 后第 1 至 14 天，每 1-3 天采集一次血样。数据应用于数学模型研究病毒动力学。可获得的肝活检样本进行 HBV 和 HDV 病毒抗原染色，并检测 HBV DNA/cccDNA。
HBsAg 和 HDV RNA 在中位数为 5 天（范围 1-13）和 4 天（范围 1-10）后分别变为阴性。所有患者的早期 HDV RNA 和 HBsAg 下降几乎完全平行；然而，数学模型显示病毒粒子死亡的变异性很高。在 LTX 后长达 19 个月，在没有肝 HBV DNA/cccDNA、血清 HBsAg 和 HDV RNA 的情况下，六名患者的移植肝中 HDAg 染色阳性。
HBV 抗原在 LTX 后最初几天内，HBV RNA 和 HBsAg 的下降遵循几乎相同的动力学模式。然而，在探索停止 HBIG 的新方法时，必须考虑 HDAg 的肝内潜伏性。
