Dienstag J L, Perrillo R P, Schiff E R, Bartholomew M, Vicary C, Rubin M
Gastrointestinal Unit, Massachusetts General Hospital, Boston 02114, USA.
N Engl J Med. 1995 Dec 21;333(25):1657-61. doi: 10.1056/NEJM199512213332501.
Better treatments for chronic hepatitis B are needed. Lamivudine, the (-)enantiomer of 3'-thiacytidine, is a potent inhibitor of hepatitis B virus (HBV).
In a double-blind trial, we randomly assigned 32 patients with chronic hepatitis B (including 17 who had no response to earlier treatment with interferon) to receive 25, 100, or 300 mg of oral lamivudine daily for 12 weeks. The patients were then followed for 24 additional weeks. All the patients had hepatitis B antigen in serum.
Levels of HBV DNA became undetectable (< or = 1.5 pg per milliliter) in 70 percent of the patients who received the 25-mg dose of lamivudine and 100 percent of those treated with the 100-mg or 300-mg dose. In most patients, HBV DNA reappeared after therapy was completed; however, six patients (19 percent), including five who had not responded to interferon, had sustained suppression of HBV DNA accompanied by normalization of alanine aminotransferase levels. Hepatitis B e antigen disappeared in four of these six patients (12 percent), three of whom had had no response to interferon. Levels of HBV DNA fell in all patients, including those who had had high levels at base line or normal alanine aminotransferase levels at base line, but sustained responses were more likely in patients with initially low HBV DNA levels and high alanine aminotransferase levels. During and after therapy, alanine aminotransferase levels at least doubled in five patients (50 percent) given the 25-mg dose and eight patients (36 percent) given the 100-mg or 300-mg dose. Minor adverse events occurred that were not related to the dose, as did transient, asymptomatic elevations of amylase, lipase, and creatine kinase levels.
In a preliminary trial, 12 weeks of lamivudine therapy was well tolerated, and daily doses of 100 mg and 300 mg reduced HBV DNA to undetectable levels.
需要更好的慢性乙型肝炎治疗方法。拉米夫定是3'-硫代胞苷的（-）对映体，是一种有效的乙型肝炎病毒（HBV）抑制剂。
在一项双盲试验中，我们将32例慢性乙型肝炎患者（包括17例对早期干扰素治疗无反应者）随机分为三组，分别每日口服25毫克、100毫克或300毫克拉米夫定，疗程为12周。之后对患者再随访24周。所有患者血清中均有乙肝抗原。
接受25毫克剂量拉米夫定治疗的患者中，70%的患者HBV DNA水平降至检测不到（≤每毫升1.5皮克），接受100毫克或300毫克剂量治疗的患者中，100%的患者HBV DNA水平降至检测不到。大多数患者在治疗结束后HBV DNA再次出现；然而，6例患者（19%），包括5例对干扰素无反应者，HBV DNA得到持续抑制，同时丙氨酸转氨酶水平恢复正常。这6例患者中有4例（12%）乙肝e抗原消失，其中3例对干扰素无反应。所有患者的HBV DNA水平均下降，包括那些基线时水平高或基线时丙氨酸转氨酶水平正常的患者，但初始HBV DNA水平低且丙氨酸转氨酶水平高的患者更有可能出现持续反应。治疗期间及治疗后，接受25毫克剂量的5例患者（50%）和接受100毫克或300毫克剂量的8例患者（36%）丙氨酸转氨酶水平至少升高一倍。出现了与剂量无关的轻微不良事件，淀粉酶、脂肪酶和肌酸激酶水平也出现了短暂的无症状升高。
在一项初步试验中，拉米夫定治疗12周耐受性良好，每日剂量100毫克和300毫克可将HBV DNA降至检测不到的水平。
