Guan Richard
Mount Elizabeth Medical Centre, Singapore.
Med J Malaysia. 2005 Jul;60 Suppl B:28-33.
Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
4至6个月的常规α干扰素（IFN-α）（每日5MU或每周三次，每次10MU）可使约33%的HBeAg阳性患者（对照组为12%）出现HBeAg转阴。延长治疗时间可提高HBeAg血清学转换率。慢性HBV感染且ALT水平高的儿童对IFN-α的反应率相似。在HBeAg阴性、HBV-DNA阳性的肝炎患者中，IFN-α治疗结束时（ET）也能实现良好的生化和病毒学反应。然而，持续反应（SR）令人失望，但随着治疗时间延长有所改善：（4/6个月治疗的SR为10 - 15%：24个月治疗的SR为30%）。每周一次聚乙二醇化α干扰素2a（PegIFN-α2a）治疗24周的HBeAg转换率（33%）显著高于常规IFN-α2a（25%）。52周的PegIFN-α2b治疗使35%的患者实现持续HBeAg转阴，29%的患者实现HBeAg血清学转换。每周一次PegIFN-α2a治疗48周也获得了类似结果。在HBeAg阴性/抗-HBe阳性的慢性乙型肝炎患者中，发现PegIFN-α2a单药治疗在实现6个月的SR（ALT正常且HBV DNA < 20,000拷贝/mL）方面优于拉米夫定单药治疗。IFN-α与拉米夫定联合治疗有比拉米夫定单药治疗产生更好持续反应的趋势。聚乙二醇化干扰素-α（PegIFN-α）与拉米夫定联合治疗也观察到这种趋势，尽管联合治疗似乎并不比PegIFN-α单药治疗更好。IFN诱导的HBeAg血清学转换是持久的，可随时间增加，并导致更好的总体生存率以及无肝失代偿或肝细胞癌的生存率。IFN-α治疗的主要优点是有限疗程可使一部分HBeAg阳性和HBeAg阴性的慢性乙型肝炎患者实现持续的停药后反应。然而，IFN治疗通常伴有副作用，尤其是流感样症状、疲劳、中性粒细胞减少、血小板减少和抑郁。这些副作用通常可以耐受，但可能需要调整剂量和提前停药（5%）。干扰素治疗诱发的肝炎发作可能导致肝硬化患者出现失代偿情况，对于肝功能失代偿的患者，尽管减少了剂量，但仍可能有危险。
