Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection
Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection
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DOI：
10.1007/s00535-016-1189-x
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发表时间：
2016-11-01
影响因子：
6.3
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
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作者：
Tsuge, Masataka;Hiraga, Nobuhiko;Chayama, Kazuaki
干扰素和核苷类药物是治疗慢性B型肝炎的主要药物。这些药物有效地降低血清B型肝炎病毒（HBV）DNA滴度，但不能充分降低B型肝炎表面抗原（HBsAg）水平。随着牛磺胆酸钠共转运多肽作为HBV进入受体的最近鉴定，抑制HBV进入已成为慢性B型肝炎治疗的有吸引力的治疗靶点。因此，我们通过体内研究和临床试验来评估抗HBsAg（anti-HBs）免疫球蛋白（HBIG）的抗病毒作用，该抗体可以抑制HBV进入，在体内研究中，由人肝细胞嵌合体小鼠产生HBV感染小鼠，并用HBIG治疗。在小鼠研究中，注射高剂量HBIG后，HBV DNA滴度降低，血清HBsAg滴度降低到无法检测的水平。在此结果的基础上，8例长期接受核苷酸类似物治疗的慢性B型肝炎患者每月注射HBIG作为额外治疗。治疗1年后，在4名患者中观察到HBsAg水平降低超过1 log IU/mL，3名患者抗-HBs呈阳性。结果提示，长期应用HBIG治疗后HBsAg滴度下降的慢性B型肝炎患者，每月注射一次HBIG可能有益。
Interferon and nucleotide/nucleoside analogues are the main treatments for chronic hepatitis B. These drugs effectively reduce serum hepatitis B virus (HBV) DNA titers but fail to sufficiently reduce hepatitis B surface antigen (HBsAg) levels. Following the recent identification of sodium taurocholate cotransporting polypeptide as a receptor for HBV entry, inhibition of HBV entry has become an attractive therapeutic target for chronic hepatitis B treatment. We therefore evaluated the antiviral effects of antibody to HBsAg (anti-HBs) immunoglobulin (HBIG), which can inhibit HBV entry, by in an vivo study and a clinical trial.In the in vivo study, HBV-infected mice were generated from human hepatocyte chimeric mice and treated with HBIG. A clinical trial evaluating HBIG therapy in patients was also performed.In the mouse study, HBV DNA titers were reduced and serum HBsAg titers decreased to undetectable levels following high-dose HBIG injection. On the basis of this result, eight chronic hepatitis B patients, who had received long-term nucleotide analogue treatment, were treated with monthly HBIG injections as an additional treatment. After 1 year of treatment, an HBsAg level reduction of more than 1 log IU/mL was observed in four patients, and three patients became anti-HBs positive. No adverse events occurred during HBIG therapy.These results suggest that monthly HBIG injection might benefit patients with chronic hepatitis B whose HBsAg titer becomes lower following long-term nucleotide/nucleoside analogue treatment.