替诺福韦治疗青少年乙肝安全、有效

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近期一项临床试验发现，成人抗病毒药物富马酸替诺福韦（替诺福韦DF）治疗青少年乙型病毒性肝炎（HBV）是安全有效的。试验结果发表在美国肝病研究协会（AASLD）的杂志《肝脏学》（12月版）上，结果显示在89%儿童参与者中替诺福韦DF能抑制HBV复制。
慢性HBV给社会造成沉重负担，研究显示，世界范围内大约有3.5亿患者，60万患者死于该种慢性疾病。疾病预防与控制中心（CDC）估计，美国有超过100万慢性HBV患者，大多数人是在幼年受到感染。医学证据表明，90%患者在婴儿阶段受到感染，其中，在1岁到4岁这段时间高达50%患者发展成慢性HBV；25%幼年感染并演变为慢性疾病的成人患者发展为肝硬化或肝癌。
“慢性HBV感染的儿童出现严重肝脏疾病（甚至死亡）的风险很高，主要是因为疾病并发症。”临床试验首席研究员、华盛顿西雅图儿童医院胃肠病和肝病科主任Karen Murray博士说，“替诺福韦DF在治疗成人慢性HBV方面卓有成效，我们的试验评价了该药对于青少年的安全性和有效性。”
该试验是一项双盲、安慰剂对照试验，涉及101名12到17岁青少年患者。受试者被随机分组，52名接受替诺福韦DF（每日300毫克剂量），54名接受安慰剂，为期72周。病毒学应答（受试者中抗病毒药物抑制病毒的能力）是此次临床试验的主要结果。试验开始前，91%参与者乙型肝炎e抗原阳性，85%曾接受过HBV治疗。
研究者发现，89%替诺福韦DF受试者出现病毒学应答，而安慰剂受试者无一人出现HBV抑制反应。在未曾接受和曾经接受过HBV治疗的青少年中，该药均能有效地抑制HBV，并且将丙氨酸氨基转移酶（ALT）降至正常范围。没有报告安全性问题，例如脊柱骨密度下降6%（安全终点）。在服用替诺福韦的受试者中没有出现耐药现象。
“在青少年患者中替诺福韦DF治疗耐受性良好，能有效抑制HBV。”Murray博士总结说，“我们的试验表明，在治疗青少年慢性HBV方面替诺福韦是一种有效的治疗。”作者指出，一项为期2年的开放性试验将进一步调查替诺福韦DF的持续反应和安全性。
在一份发表在《肝病学》杂志上的社论中，旧金山加州大学（UCSF）的Philip Rosenthal博士提出了一个问题，怎样才能避免慢性乙型病毒性肝炎儿童患者发展成肝病和肝癌。“不久前用于治疗HBV的药物还十分有限，很高兴能见到抗争这种疾病的药物在逐渐增多，而且还能获批应用于儿童和青少年。”Rosenthal博士说，“Murray等人的研究仅限于青少年，未来替诺福韦DF的研究将在更小的儿童中进行。”

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A recent clinical trial found that the adult antiviral drug, tenofovir disoproxil fumarate (tenofovir DF), is safe and effective in treating adolescents with hepatitis B virus (HBV). Trial results published in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD), show that tenofovir DF suppressed HBV in 89% of pediatric participants.

Chronic HBV is a major health burden that studies estimate affects 350 million people worldwide, with 600,000 deaths attributed to this chronic disease. The Centers for Disease Control and Prevention (CDC) estimate that more than one million Americans have chronic HBV, with most patients infected during childhood. Medical evidence suggests that 90% of patients infected as infants, and up to 50% infected between one and four years of age develop chronic HBV; 25% of adults who become chronically infected in childhood develop cirrhosis or liver cancer.

"Children chronically infected with HBV are at great risk of developing severe liver disease and possible death due to complications from the disease," said Dr. Karen Murray, Chief of the Division of Gastroenterology and Hepatology at Seattle Children's Hospital in Washington and lead researcher of the clinical trial. "Tenofovir DF is highly effective in treating adults with chronic HBV and our trial evaluated safety and efficacy of the drug in adolescents."

This double-blind, placebo-controlled trial was conducted in 101 adolescents aged 12 to 17 years. Participants were randomized with 52 receiving a daily 300 mg dose of tenofovir DF and 54 taking a placebo for 72 weeks. A virologic response - ability of the antiviral medication to suppress the virus in participants - was the main outcome of this clinical trial. At the onset of the trial 91% of participants tested positive for the hepatitis B e-antigen and 85% received prior HBV therapy.

Researchers observed a virologic response in 89% of participants who received tenofovir DF, while none of the patients in the placebo group achieved HBV suppression. The drug successfully suppressed HBV and normalized alanine aminotransferase (ALT) levels in both adolescents who received no prior treatment and in those previously exposed to HBV therapy. No safety issues, such as a 6% reduction in spine bone density (safety end point), were reported. Trial participants taking tenofovir showed no resistance to the drug.

"Tenofovir DF therapy was well tolerated and effective in suppressing HBV in adolescents," concludes Dr. Murray. "Our trial demonstrates that tenofovir is a beneficial therapy for managing chronic HBV in teens." The authors note that a two-year open-label phase study will further investigate the sustained response and safety of tenofovir DF.

In an editorial also published in Hepatology, Dr. Philip Rosenthal with the University of California, San Francisco (UCSF) questions what can be done to alter the development of liver disease and liver cancer in children with chronic hepatitis B infection. "It was not long ago that drugs to treat HBV were limited and it is gratifying to see an increase in medications to combat this disease being approved for use in children and teens," said Dr. Rosenthal. "While the study by Murray et al. was limited to adolescents, future study of tenofovir DF in younger children is underway."