Hepatology：替诺福韦酯治疗青少年HBV感染安全有效

近期公布的一项临床试验结果表明，成人用抗病毒药物替诺福韦酯（tenofovir DF）可安全有效地治疗青少年HBV感染。研究表明，替诺福韦酯对HBV的抑制率达89%，该结果发表于今年12月的《肝病学》（Hepatology）杂志上，该杂志隶属于美国肝病研究协会。

慢性HBV感染给全球健康带来巨大的负担，共有3.5亿人感染HBV，其中有60万人死于这种疾病。疾病控制中心（CDC）估计，超过100万美国人感染慢性HBV，大多数都是在幼年时期感染。医学证据表明，大约90%患者感染于婴儿时期，感染于1至4岁之间的患者中超过半数发展为慢性HBV；于幼年时期感染的成人患者中有25%发展为肝硬化或肝癌。华盛顿州西雅图市儿童医院胃肠病学和肝病学科主负责人KarenMurray说：“感染慢性HBV的儿童发展为严重肝脏疾病的风险较高，并且致死率也高。替诺福韦酯能够非常有效地治疗成人慢性HBV感染，我们的试验旨在评估这种药物在青少年身上的安全性和有效性。”

本项随机双盲安慰剂对照临床试验共纳入了101名年龄在12至17周岁之间的青少年患者。该试验持续72周，在试验过程中，受试者被随机分配，其中52名青少年接受每日300mg剂量的替诺福韦酯，剩下的患者接受安慰剂。此项临床试验的主要终点是抗病毒药物的病毒应答能力对HBV的抑制效果。在实验开始前，91%的受试者为HBeAg阳性，85%既往接受过乙肝治疗。研究人员发现，替诺福韦酯治疗组89%的受试患者出现病毒学应答，而安慰剂组所有患者均未出现HBV抑制。在治疗组中，替诺福韦酯能够有效抑制HBV增殖并使谷丙转氨酶恢复到正常范围，这种疗效在既往有或无乙肝治疗史的患者身上均得到验证。没有报道出现安全性问题，实验人群亦未出现耐药现象。

Murray博士称：“替诺福韦酯治疗青少年HBV感染表现出良好的耐受性和有效性，试验证明了替诺福韦对青少年慢性HBV的病情控制是有益的。”他还透露，将有一项为期两年的开放性试验研究对替诺福韦DF的持续性病毒学应答和安全性作进一步研究。

该杂志也刊登了加州大学旧金山分校的Philip Rosenthal博士撰写的一篇评论性文章，对应采取何种手段才能改变那些慢性HBV感染儿童发展为肝病和肝癌的进程提出疑问。Rosenthal说：“不久前，治疗HBV的药物还很有限，但如今我们很欣喜地发现被批准用于儿童和青少年的治疗药物的增加。然而Murray等人的研究只限于青少年人群，有关替诺福韦酯用于更小年龄儿童的进一步研究还正在进行中。”

与替诺福韦酯相关的拓展阅读：

• Lancet：长期替诺福韦酯治疗可逆转慢乙肝肝硬化

DOI: 10.1002/hep.25818
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Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B

Karen F. Murray1,¶,*, Leszek Szenborn2, Jacek Wysocki3, Stephen Rossi4, Amoreena C. Corsa4, Phillip Dinh4, John McHutchison4, Phillip S. Pang4, Luminita M. Luminos5, Malgorzata Pawlowska6, Jacek Mizerski7

Tenofovir disoproxil fumarate (DF) is highly effective for the suppression of hepatitis B virus (HBV) in chronically infected adults. This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B (CHB). In this double-blind, placebo-controlled trial, adolescents 12 to <18 years of age with CHB were randomized to tenofovir DF 300 mg (n = 52) or placebo (n = 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL) at week 72. One hundred six patients were enrolled; 101 patients completed 72 weeks of treatment. At baseline, 91% of patients were hepatitis B e antigen–positive and 85% had prior exposure to HBV therapy. A virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) level greater than the upper limit of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72. Conclusion: Tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment-naïve adolescents and those with prior exposure to HBV therapy.