Pol S, Couillin I, Michel M L, Driss F, Nalpas B, Carnot F, Berthelot P, Bréchot C
Unité d'Hépatologie, Hôpital Necker, Paris, France.
Acta Gastroenterol Belg. 1998 Apr-Jun;61(2):228-33.
Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, their possible side effects and the immune-mediated pathology of HBV infection explain the need of new immune therapies in treating HBV infection. Experimental and clinical evidences suggest the usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened study, forty-six consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month interval. Six months after the first injection, 12 patients (26.1%) had undetectable HBV DNA while 8 others showed significant decrease (more than 50%) in HBV DNA titers. Six of these 12 responders received a standard course of alpha-Interferon (5 MU thrice weekly subcutaneously for 4 months) and all six had still undetectable HBV replication at the end of follow-up. Among the 34 non responders to vaccine, 20 were given alpha-interferon and 2 the monophosphate derivate of Vidarabine: 12 of these 22 patients stopped HBV replication and in all 12, vaccine therapy had induced a significant decrease of HBV replication before the antiviral treatment with a decrease of mean serum HBV DNA from 392 pg/ml before to 217 pg/ml after vaccine therapy. In an ongoing controlled study, using the same vaccine schedule, serum HBV DNA disappeared more frequently after 6 months, in patients who were given a preS2/S vaccine (7/35) than in patients who received a S vaccine (1/21) or no vaccine (1/32). In responders to vaccine, an induction of specific proliferative responses was observed and this may contribute to the potential efficacy of anti-HBV vaccine therapy. No side-effect or vaccine-induced escape-mutants occurred during the follow-up. In summary, serum HBV DNA disappeared in 28 of the 46 patients (60.9%) who were given vaccine therapy, with (64.2%) or without (55.6%) Interferon. These results are not different at 6 months and at the end of follow-up from those of 43 HBsAg chronic carriers who were given only an antiviral treatment. Active immune therapy against HBV appears efficient and less expensive than antiviral therapies in stopping HBV replication. Such results need to be confirmed by the completed results of our controlled, randomized trial which is now conducted in our unit.
疫苗疗法目前已应用于多种传染病。乙型肝炎病毒（HBV）可导致约5%的患者发生慢性感染，这些患者发生慢性活动性肝炎的风险较高，而慢性活动性肝炎可能会发展为肝硬化和肝细胞癌。抗病毒疗法存在部分疗效（40%的患者可实现HBV复制的持续抑制）、费用高昂、可能产生副作用以及HBV感染的免疫介导病理等问题，这些都表明在治疗HBV感染时需要新的免疫疗法。实验和临床证据表明疫苗疗法对HBV慢性感染有效。在一项初步的开放性研究中，连续纳入46例患有慢性肝炎且血清HBV DNA可检测到的慢性HBsAg携带者，每隔一个月给予3次标准剂量的GenHevac B疫苗注射。首次注射后6个月，12例患者（26.1%）的HBV DNA检测不到，另有8例患者的HBV DNA滴度显著下降（超过50%）。这12例有反应的患者中有6例接受了标准疗程的α干扰素治疗（皮下注射5 MU，每周3次，共4个月），随访结束时所有6例患者的HBV复制仍检测不到。在34例对疫苗无反应的患者中，20例接受了α干扰素治疗，2例接受了阿糖腺苷单磷酸盐治疗：这22例患者中有12例停止了HBV复制，在所有12例患者中，疫苗疗法在抗病毒治疗前显著降低了HBV复制，血清HBV DNA的平均水平从疫苗治疗前的392 pg/ml降至治疗后的217 pg/ml。在一项正在进行的对照研究中，采用相同的疫苗接种方案，接种前S2/S疫苗的患者（7/35）在6个月后血清HBV DNA消失的频率高于接种S疫苗的患者（1/21）或未接种疫苗的患者（1/32）。在对疫苗有反应的患者中，观察到了特异性增殖反应的诱导，这可能有助于抗HBV疫苗疗法的潜在疗效。随访期间未出现副作用或疫苗诱导的逃逸突变体。总之，在接受疫苗治疗的46例患者中，28例（60.9%）的血清HBV DNA消失，其中联合（64.2%）或未联合（55.6%）干扰素治疗。这些结果在6个月时以及随访结束时与仅接受抗病毒治疗的43例HBsAg慢性携带者的结果无差异。针对HBV的主动免疫疗法在阻止HBV复制方面似乎有效且比抗病毒疗法成本更低。这些结果需要通过我们单位正在进行的对照随机试验的完整结果来证实。
