Lancet infect dis：急性丙型肝炎的延迟治疗与立即治疗

一项来自德国的随机对照非劣效性试验表明，对于急性丙型肝炎病毒(HCV)感染，延迟治疗有效。该研究于2013年3月21日在线发表于《柳叶刀·传染病学》杂志（Lancet Infectious Diseases）。
　　HCV感染早期应用干扰素-α治疗非常有效，治愈率可达85%以上。然而，有10—50%的病例会发生HCV的自发性清除。该研究旨在评估对于未自发性清除病毒的患者采用备选方案的延迟抗病毒治疗与立即治疗的疗效。
　　结论是，尽管延迟治疗的疗效与立即治疗的疗效并不相等，但延迟治疗是有效的，加上自发性病毒清除率，延迟治疗能够减少密切监测人群的不必要治疗。而立即治疗似乎对于失访比例较大的人群更可取。
与HCV相关的拓展阅读：

• BMC Med：IL28B为HCV个体化治疗提供有效帮助
• JAMA：SVR与慢性HCV感染的存活率改善相关
• CLIN INFECT DIS：干扰素联合利巴韦林治儿童HCV安全有效
• HIV患者的HCV感染可被安全治疗
• J Biol Chem：研究发现HCV损害肝脏的线索
• J Gastroenterol Hepatol：HCV血清阳性与糖尿病相关 更多信息请点击：有关HCV更多资讯

Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial.
BACKGROUND
Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.
METHODS
In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946.
FINDINGS
Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI -4·6 to 32·0; p=0·071). 18 (72%) of 25 asymptomatic patients had a sustained virological response. 22 (42%) of 52 symptomatic patients allocated to receive delayed treatment did not complete follow-up compared with 20 (25%) of 80 symptomatic or asymptomatic patients assigned immediate treatment (p=0·037). 11 symptomatic patients (21%) assigned delayed treatment had spontaneous HCV clearance. 14 patients who received delayed pegylated interferon alfa-2b plus ribavirin treatment and completed follow-up achieved sustained virological response.
INTERPRETATION
Delayed treatment is effective although not of equal efficacy to immediate treatment; coupled with the rate of spontaneous clearance it can reduce unnecessary treatment in closely monitored populations. Immediate treatment seems preferable in populations where loss to follow-up is great.
FUNDING
German Network of Competence on Viral Hepatitis (HepNet, funded by the German Federal Ministry of Education and Research, grants 01KI0102, 01KI0401, and 01KI0601), MSD, Schering-Plough.