Lim Seng Gee, Ng Tay Meng, Kung Nelson, Krastev Zahary, Volfova Miroslava, Husa Petr, Lee Samuel S, Chan Sing, Shiffman Mitchell L, Washington Mary Kay, Rigney Amy, Anderson Jane, Mondou Elsa, Snow Andrea, Sorbel Jeff, Guan Richard, Rousseau Franck
National University Hospital, Singapore.
Arch Intern Med. 2006 Jan 9;166(1):49-56. doi: 10.1001/archinte.166.1.49.
Emtricitabine is a nucleoside analogue approved for treatment of human immunodeficiency virus 1 with clinical activity against hepatitis B virus (HBV).
To compare the safety and efficacy of emtricitabine with placebo in patients with HBV, we conducted a randomized (2:1), double-blind study at 34 sites in North America, Asia, and Europe that enrolled adults between November 2000 and July 2002 who had chronic HBV infection but had never been exposed to nucleoside or nucleotide treatment. Each patient received either 200 mg of emtricitabine (n=167) or placebo (n=81) once daily for 48 weeks and underwent a pretreatment and end-of-treatment liver biopsy. Histologic improvement was defined as a 2-point reduction in Knodell necroinflammatory score with no worsening in fibrosis.
At the end of treatment, 103 (62%) of 167 patients receiving active treatment had improved liver histologic findings vs 20 (25%) of 81 receiving placebo (P<.001), with significance demonstrated in subgroups positive (P<.001) and negative (P=.002) for hepatitis Be (HBe) antigen. Serum HBV DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001); alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81), respectively (P<.001). At week 48, 20 (13%) of 159 patients in the emtricitabine group with HBV DNA measured at the end of treatment had detectable virus with resistance mutations (95% confidence interval, 8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss were not different between arms. The safety profile of emtricitabine during treatment was similar to that of placebo. Posttreatment exacerbation of HBV infection developed in 23% of emtricitabine-treated patients.
In patients with chronic HBV, both positive and negative for HBe antigen, 48 weeks of emtricitabine treatment resulted in significant histologic, virologic, and biochemical improvement.
恩曲他滨是一种核苷类似物，已被批准用于治疗人类免疫缺陷病毒1，对乙型肝炎病毒（HBV）具有临床活性。
为比较恩曲他滨与安慰剂对HBV患者的安全性和疗效，我们在北美、亚洲和欧洲的34个地点进行了一项随机（2:1）、双盲研究，纳入了2000年11月至2002年7月期间患有慢性HBV感染但从未接受过核苷或核苷酸治疗的成年人。每位患者每天接受一次200mg恩曲他滨（n = 167）或安慰剂（n = 81），持续48周，并在治疗前和治疗结束时进行肝脏活检。组织学改善定义为Knodell坏死性炎症评分降低2分且纤维化无恶化。
治疗结束时，167例接受活性治疗的患者中有103例（62%）肝脏组织学检查结果改善，而81例接受安慰剂治疗的患者中有20例（25%）改善（P <.001），在乙型肝炎e（HBe）抗原阳性（P <.001）和阴性（P =.002）亚组中均有显著差异。恩曲他滨组167例患者中有91例（54%）血清HBV DNA读数低于400拷贝/mL，而安慰剂组81例中有2例（2%）（P <.001）；丙氨酸转氨酶水平正常的比例分别为65%（109/167）和25%（20/81）（P <.001）。在第48周时，恩曲他滨组159例在治疗结束时检测HBV DNA的患者中有20例（13%）检测到带有耐药突变的病毒（95%置信区间，8% - 18%）。两组之间抗-HBe血清转换率（12%）和HBe抗原消失率无差异。恩曲他滨治疗期间的安全性与安慰剂相似。23%接受恩曲他滨治疗的患者出现治疗后HBV感染恶化。
在HBe抗原阳性和阴性的慢性HBV患者中，48周的恩曲他滨治疗导致组织学、病毒学和生化方面的显著改善。
