結合疫苗與拉米夫定療法將有助於慢性B型肝炎

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結合疫苗與拉米夫定療法將有助於慢性B型肝炎 作者：Laurie Barclay, MD 出處：WebMD醫學新聞審閱：Gary D. Vogin, MD 　　Nov. 4, 2003－根據一篇在波士頓舉辦的第54屆美國肝臟疾病研究協會10月28日的報告顯示，結合拉米夫定與疫苗療法能增進慢性B型肝炎的療效。 　　 　　第一作者，來自日本Ehime大學醫學院Sk. Md. Fazle Akbar向Medscape表示，B型肝炎病毒與宿主對HBV的免疫反應都是慢性B型肝炎發病的原因，大部分無症狀的HBV帶原者不論其血清或肝臟的HBV濃度多少都不會顯現出肝炎症狀的這項事實更能進一步地支持這項論點，對於慢性HBV的感染需要免疫療法以補充抗病毒療法。 　　 　　這項研究包含了經由臨床診斷、生化及血清學數據及肝切片檢查的組織學特徵診斷為慢性B型肝炎的72位病患，所有的研究對象接受持續12個月的每日口服100mg干安能，其中15位在開始服用拉米夫定干安能後的三個月開始接受含有20μgB型肝炎表面抗原疫苗的皮下注射，每兩週一次，共12劑。 　　 　　在為期12個月的治療後，所有接受合併治療的15位病患（100%）及57位接受拉米夫定干安能單一治療病患中的37位（67%）血清檢驗HBV DNV為陰性(P < .05)。 　　 　　接受合併治療組中有55%的血清轉變由HbeAg變為anti-Hbe，接受拉米夫定干安能單一治療組則為16%(P < .05)，接受合併治療的病患沒有HBV DNA或肝炎的突破性發展，而在接受拉米夫定干安能單一治療組中有10位病患有HBV DNA進展，及4位肝炎加劇。 　　 　　為了測定這些研究發現的免疫學根據，研究人員以不同的白血球反應及組織培養中的白細胞介素（IL）-12來評估被定義為lineage-，末梢血液中的CD4+，及HLA DR+ cells的antigen-presenting dendritic cells (DCs)功能。 　　 　　在接受疫苗的病患中，DCs的刺激量及由DCs 所產生的IL-12在開始接受疫苗治療一個月後明顯高於先前(P < .05)，且在接受疫苗療法的整個期間持續升高。 　　 　　Sk. Md. Akbar參考他早期關於在鼠科動物HBV帶原者的DC基礎疫苗研究及先前在慢性B型肝炎病患的正常自願者DC基礎疫苗臨床試驗後表示，DCs是免疫療法的影響因素，疫苗療法會活化DCs及幫助誘發原有的及適合的免疫力。 　　 　　他做出總結，我相信以抗病毒加上以DC做為基礎的免疫療法對於治療慢性B型肝炎是一項完美的治療方法，最特別的是，這項治療方法的原理可以運用在其他持續感染及惡化。 　　

Combination Vaccine-Lamivudine Therapy Helpful in Chronic Hepatitis B

By Laurie Barclay, MD Medscape Medical News

Nov. 4, 2003 — Combining vaccine therapy with lamivudine has improved therapeutic potential for chronic hepatitis B, according to a presentation on Oct. 28 at the 54th annual meeting of the American Association for the Study of Liver Diseases held in Boston, Massachusetts.

"Both hepatitis B virus (HBV) and the immune response of the host to HBV are responsible for the pathogenesis of chronic hepatitis B. This is further supported by the fact that most of the asymptomatic carriers of HBV do not show features of hepatitis in spite of high levels of HBV in their sera and liver," lead author Sk. Md. Fazle Akbar, from the Ehime University School of Medicine in Japan, told Medscape. "There is a need for immune therapy [to supplement] antiviral therapy for chronic HBV infection."

This study enrolled 72 patients with chronic hepatitis B diagnosed from clinical symptoms, biochemical and serological data, and histological features on liver biopsy. All subjects received oral lamivudine, 100 mg/day, for 12 months, and 15 also received vaccine containing 20 µg hepatitis B surface antigen, given intradermally, once every two weeks for 12 doses, beginning three months after starting lamivudine.

After 12 months of therapy, all 15 patients (100%) receiving combination therapy and 39 (67%) of 57 patients receiving lamivudine monotherapy became seronegative for HBV DNA (P < .05) Seroconversion from HBeAg to anti-HBe occurred in 55% of the combination therapy group and in 16% of the lamivudine monotherapy group (P < .05). No patients receiving combination therapy had breakthrough of HBV DNA or breakthrough hepatitis, which occurred in the lamivudine monotherapy group in 10 patients and in four patients, respectively.

To determine the immunological basis of these findings, the functions of antigen-presenting dendritic cells (DCs), defined as lineage-, CD4+, and HLA DR+ cells of the peripheral blood, were evaluated in allogenic mixed leukocyte reaction and by their production of interleukin (IL)-12 in culture.

In patients receiving the vaccine, the stimulatory capacity of DCs and IL-12 production by DCs were significantly higher one month after the start of vaccine therapy than at baseline (P < .05) and remained elevated for the entire duration of vaccine therapy.

"[DCs] represent a potent candidate for immune therapy. Vaccine therapy activates DCs and helps to induce innate as well as adaptive immunity," Sk. Md. Akbar said, referencing his earlier study of a DC-based vaccine in murine HBV carriers, and a previous clinical trial in normal volunteers of a DC-based vaccine for patients with chronic hepatitis B.

"I believe that antiviral plus DC-based immune therapy would be an excellent mode of therapy for chronic HBV infection," he concluded. "Most notably, the principle of this therapeutic approach could be used for other persistent infection and malignancies."

This study was not supported by any organization or company, and the authors report no financial disclosures.

AASLD 54th Annual Meeting. Presented Oct. 28, 2003.

Reviewed by Gary D. Vogin, MD