Wolters L M, van Nunen A B, Honkoop P, Vossen A C, Niesters H G, Zondervan P E, de Man R A
Department of Hepatogastroenterology, Erasmus University Hospital, Rotterdam, The Netherlands.
J Viral Hepat. 2000 Nov;7(6):428-34. doi: 10.1046/j.1365-2893.2000.00254.x.
Currently, the best option for patients with hepatitis delta is interferon alpha therapy for at least one year. To evaluate the effect of the combination lamivudine-high-dose interferon alpha therapy, we first treated eight patients with chronic hepatitis delta infection with lamivudine for at least 24 weeks; then lamivudine was combined with a high dose of interferon alpha followed by a regular dose (9 MU tiw). Follow-up was 12 weeks. Virological, biochemical and histological features were evaluated for response to therapy. At baseline, all patients were HBsAg positive in serum and HDV RNA-(PCR)positive in plasma; HBV DNA was undetectable with the Digene Hybrid Capture assay (limit of detection 1.5 x 10(6) geq ml-(1)) in all cases. Transaminases were elevated in all patients; median ALT 68 (range 48-143) IU l(1). Seven of eight patients completed the course; one patient with a pre-existing sickle cell trait was withdrawn from the trial due to the development of a nephrotic syndrome. The HBsAg-concentration in serum decreased in two out of seven patients (29%). However, there was no significant decrease in the HBsAg-concentration in serum during treatment (median 3654 PEU l(-1) (range 548-7,684) to 5300 PEU l(-1) (range 168-19,639)). The drop of HDV RNA in plasma from baseline during treatment was not significant. Decrease of HDV RNA was observed in three out of seven patients (43%) (median 10(5) geq ml(-1); range 10(3)-10(6) to median 10(3) geq ml(-1); range 10(2)-10(7)). Serum ALT did not change as reflected by a median of 68 IU l(-1) (range 48-143) at start of therapy to 63 IU l(-1) (range 20-171) at the end of therapy. At the end of treatment transaminases had normalised in one patient and decreased in three other patients (improvement in 57%). However, three of these four patients showed a rebound after withdrawal of therapy. The Histology Activity Index (HAI) indicated a drop from a median score of 7 (range 5-9) at baseline to 5 (range 3-8) at the end of treatment, but an increase in fibrosis from a median grade of 2 (range 1-3) at baseline to 3 (range 1-4) at the end of treatment was observed. In conclusion, this study does not yield support for the combination of an HBV suppressor and 16 weeks of high-dose interferon for therapy aimed at eradicating the hepatitis delta virus.
目前，对于丁型肝炎患者，最佳选择是使用α干扰素治疗至少一年。为评估拉米夫定联合大剂量α干扰素治疗的效果，我们首先对8例慢性丁型肝炎感染患者使用拉米夫定治疗至少24周；然后将拉米夫定与大剂量α干扰素联合使用，随后使用常规剂量（9MU，每周3次）。随访12周。评估病毒学、生化和组织学特征以判断治疗反应。基线时，所有患者血清HBsAg阳性，血浆HDV RNA（PCR法）阳性；所有病例中，Digene杂交捕获试验均未检测到HBV DNA（检测下限为1.5×10⁶ geq/ml⁻¹）。所有患者转氨酶均升高；ALT中位数为68（范围48 - 143）IU/l⁻¹。8例患者中有7例完成了疗程；1例患有镰状细胞性状的患者因肾病综合征的发生退出试验。7例患者中有2例（29%）血清HBsAg浓度下降。然而，治疗期间血清HBsAg浓度无显著下降（中位数从3654 PEU/l⁻¹（范围548 - 7684）降至5300 PEU/l⁻¹（范围168 - 19639））。治疗期间血浆HDV RNA较基线的下降不显著。7例患者中有3例（43%）观察到HDV RNA下降（中位数从10⁵ geq/ml；范围10³ - 10⁶降至中位数10³ geq/ml；范围10² - 10⁷）。血清ALT未发生变化，治疗开始时中位数为68 IU/l⁻¹（范围48 - 143），治疗结束时为63 IU/l⁻¹（范围20 - 171）。治疗结束时，1例患者转氨酶恢复正常，另外3例患者转氨酶下降（改善率为57%）。然而，这4例患者中有3例在治疗停药后出现反弹。组织学活动指数（HAI）显示从基线时的中位数7分（范围5 - 9）降至治疗结束时的5分（范围3 - 8），但纤维化程度从基线时的中位数2级（范围1 - 3）升至治疗结束时的3级（范围1 - 4）。总之，本研究不支持将一种HBV抑制剂与16周大剂量干扰素联合用于旨在根除丁型肝炎病毒的治疗。
