Entecavir Treatment of Chronic Hepatitis D
Entecavir Treatment of Chronic Hepatitis D
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DOI：
10.1093/cid/cis459
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发表时间：
2012-09-01
影响因子：
11.8
通讯作者：
Yurdaydin, Cihan
中科院分区：
文献类型：
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作者：
Kabacam, Gokhan;Onder, F. Oguz;Yurdaydin, Cihan
背景丁型肝炎病毒（HDV）需要B型肝炎表面抗原（HBsAg）来传播感染并引起疾病。恩替卡韦是一种具有强效抗病毒功效的核苷类似物，在土拨鼠动物模型中，它还可降低B型肝炎病毒（HBV）cccDNA和土拨鼠表面抗原。本研究旨在探讨恩替卡韦治疗慢性丁型肝炎（CHD）的疗效。这项单中心研究在代偿性肝病患者中进行。所有患者都必须有可检测的肝炎HDV RNA和丙氨酸氨基转移酶（ALT）水平升高。恩替卡韦以1 mg/d的剂量给药1年。主要终点是在治疗结束时达到检测不到HDV RNA。对13名连续患者进行了评估。所有患者在基线时均可检测到HDV RNA，8例可检测到HBV DNA。在治疗结束时，HBV DNA在所有患者中变得不可检测（P = .001）。未观察到HDV RNA、ALT或定量HBsAg水平显著下降。治疗结束时，3例基线HDV RNA水平显著低于无应答者（2.99 log 10拷贝/mL +/- .70 vs 4.68 +/- .97; P = .0185）的患者达到了HDV RNA检测不到的主要终点。在所有3例患者中，ALT水平在治疗结束时也正常。恩替卡韦治疗冠心病一年无效。核苷/核苷酸类似物治疗的任何普遍有益效果可能需要延长治疗。HBV占优势的CHD患者可能发生在CHD的晚期，可能是靶向核苷/核苷酸类似物治疗的合理患者队列。
Background. Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD).Methods. This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment.Results. Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log10 copies/mL +/- .70 vs 4.68 +/- .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment.Conclusions. One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.