Yano Yoshihiko, Seo Yasushi, Hayashi Hiroki, Hatazawa Yuri, Hirano Hirotaka, Minami Akihiro, Kawano Yuki, Saito Masaya, Ninomiya Toshiaki, Sugano Masahiko, Yamada Hajime, Kitajima Naoto, Yoon Seitetsu, Hayashi Yoshitake
Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Biomed Rep. 2017 Sep;7(3):257-262. doi: 10.3892/br.2017.944. Epub 2017 Jul 18.
The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P<0.05). Moreover, an increase in alanine aminotransferase (ALT) of >2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, P<0.05). The proportion of patients with a decrease in HBsAg was significantly greater in patients who received IFN monotherapy than in patients who received IFN and ADV combination therapy (43 vs. 29%, P<0.05). The present results revealed that the HBcr antigen titer before therapy and an on-treatment elevation of ALT (indicative of host instruction flare) are important factors associated with a decrease in HBsAg titers after IFN-based therapy. The efficacy of IFN and ADV combination therapy was not apparent in terms of a reduction in the HBsAg titer.
慢性乙型肝炎（CHB）抗病毒治疗的目的通常是使乙肝表面抗原（HBsAg）减少并最终消失。CHB的干扰素（IFN）治疗在亚洲国家似乎不如在欧洲国家有效，IFN与核苷（酸）类似物（NA）联合治疗的优势尚未得到充分研究。本研究聚焦于IFN单药治疗或IFN + NA联合治疗后与HBs抗原减少相关的因素。本研究共纳入35例接受基于IFN治疗的CHB患者（平均年龄±标准差为36.7±8.5岁；男性27例，女性8例）。在这35例患者中，21例接受聚乙二醇化IFN单药治疗，14例接受IFN与阿德福韦（ADV）联合治疗。我们研究了与治疗结束时及治疗后24周时HBsAg滴度从初始HBsAg滴度降低>1.0 log IU/ml相关的因素。尽管13例患者（37%）在治疗结束时HBsAg降低>1.0 IU/ml，但仅7例患者（20%）在治疗后24周时仍保持该水平。治疗结束时HBsAg降低的患者治疗前的乙肝核心相关抗原（HBcrAg）滴度显著高于HBsAg未降低的患者（6.56±0.78 vs. 5.30±1.66 log IU/ml，P<0.05）。此外，HBsAg降低的患者中丙氨酸氨基转移酶（ALT）较基线升高>2倍的情况显著更常见（62% vs. 14%，P<0.05）。接受IFN单药治疗的患者中HBsAg降低的比例显著高于接受IFN与ADV联合治疗的患者（43% vs. 29%，P<0.05）。目前的结果显示，治疗前的HBcr抗原滴度以及治疗期间ALT升高（提示宿主指导下的免疫激活）是基于IFN治疗后HBsAg滴度降低的重要相关因素。就降低HBsAg滴度而言，IFN与ADV联合治疗的疗效并不明显。
