Mellerup M T, Krogsgaard K, Mathurin P, Gluud C, Poynard T
Hegnsvej 127, Naerum, Denmark, DK-2850.
Cochrane Database Syst Rev. 2005 Jul 20;2005(3):CD000345. doi: 10.1002/14651858.CD000345.pub2.
Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon.
The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B 'e' antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events.
Eligible trials were identified through searches of The Cochrane Hepato-Biliary Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (Excerpta Medica Database) (1980 to May 2005), BIOSIS (1969 to May 2005), and reference lists of relevant articles. Further trials were sought through correspondence with authors of trials and pharmaceutical companies.
Randomised clinical trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. We included trials irrespective blinding, publication status, or language.
Three authors selected the trials independently and one extracted the data, which were then validated. We performed assessments of the outcome measures at the end of treatment and at six months and at maximal follow-up after the end of treatment with alfa interferon.
We included a total of 13 randomised trials with 790 patients. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data.
AUTHORS' CONCLUSIONS: Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.
慢性乙型肝炎对发病率和死亡率有严重影响。已证明α干扰素可提高HBeAg清除率以及抗HBe血清转换率，但应答率并不理想。糖皮质激素预处理可能会增加对α干扰素的应答。
评估糖皮质激素与α干扰素序贯联合治疗与单独使用α干扰素治疗对HBeAg阳性慢性乙型肝炎患者的死亡率、病毒学应答、生化应答、肝脏组织学、生活质量和不良事件的影响。
通过检索Cochrane肝胆对照试验注册库（2005年5月）、Cochrane图书馆中的Cochrane对照试验中心注册库（2005年第2期）、MEDLINE（1950年至2005年5月）、EMBASE（医学文摘数据库）（1980年至2005年5月）、BIOSIS（1969年至2005年5月）以及相关文章的参考文献列表来确定符合条件的试验。通过与试验作者和制药公司通信来寻找更多试验。
比较相同α干扰素治疗方案在有或无糖皮质激素预处理情况下治疗HBeAg阳性慢性乙型肝炎的随机临床试验。我们纳入的试验不考虑是否采用盲法、发表状态或语言。
三位作者独立选择试验，一位提取数据，然后进行验证。我们在治疗结束时、治疗结束后6个月以及α干扰素治疗结束后的最长随访期对结局指标进行评估。
我们共纳入13项随机试验，涉及790例患者。在接受糖皮质激素与α干扰素序贯联合治疗的患者中，HBeAg消失（比值比1.41，95%置信区间1.03至1.92，P = 0.03）和乙肝病毒DNA消失（比值比 = 1.51，95%置信区间1.12至2.05，P = 0.008）的情况比单独接受α干扰素治疗的患者更为常见。糖皮质激素预处理对HBeAg向抗HBe血清转换、乙肝表面抗原消失、丙氨酸氨基转移酶/天冬氨酸氨基转移酶活性正常化以及不良事件严重程度没有显著影响。糖皮质激素预处理对死亡率和不良事件没有显著影响。由于数据不足，无法评估糖皮质激素预处理对肝脏组织学和生活质量的影响。
对于HBeAg阳性慢性乙型肝炎患者，在使用α干扰素治疗前进行糖皮质激素预处理在HBeAg和乙肝病毒DNA消失方面可能比单独使用α干扰素治疗更有效，但缺乏对临床结局有影响的证据。
