Sheldon Julie, Ramos Belén, Toro Carlos, Ríos Pilar, Martínez-Alarcón José, Bottecchia Marcelle, Romero Miriam, Garcia-Samaniego Javier, Soriano Vincent
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Antivir Ther. 2008;13(1):97-102.
Hepatitis delta virus (HDV) has a unique replication process that requires coinfection with hepatitis B virus (HBV). Treatment is currently limited to interferon therapy. The role of potent nucleos(t)ide analogues active against HBV has not been well examined in chronic delta hepatitis (CDH).
HIV-positive patients with CDH attending our hospital were identified and longitudinally studied. Serum HBV DNA, HDV RNA and HIV RNA, treatment regimens, and biochemical and serological markers were assessed at yearly intervals. Liver fibrosis was measured by transient elastography during the last 2 years.
Sixteen patients were identified and treated with anti-HBV therapy (median time 6.1 years). The majority were male and previous intravenous drug users. Median baselines were: HDV RNA 7 log10 copies/ml, HIV RNA 1.7 log10 copies/ml, HBV DNA 1.1 log10 IU/ml and alanine aminotransferase (ALT) 98 IU/ml. A significant correlation was found between HDV RNA and HBV DNA (r=0.226, P=0.015), aspartate aminotransferase (r=0.430, P<0.0001), ALT (r=0.441, P<0.0001) and hepatitis B surface antigen (HBsAg) (r=0.557, P<0.0001). Overall, 13 patients showed a reduction in HDV viraemia and ALT levels, and three of them achieved undetectable HDV RNA and normal ALT levels.
Patients undergoing successful anti-HBV therapy with potent nucleos(t)ide analogues seem to indirectly benefit from suppression of HDV replication, albeit not very efficiently. Hypothetically, a significant and sustained reduction in serum HDV RNA might only be seen when a reduction in HBV covalently closed circular DNA or HBV surface antigen is achieved, which may require long periods of successful anti-HBV therapy. To our knowledge, this is the first evidence of the benefit of potent anti-HBV nucleos(t)ide analogue therapy in CDH.
丁型肝炎病毒(HDV)具有独特的复制过程,需要与乙型肝炎病毒(HBV)同时感染。目前的治疗仅限于干扰素疗法。强效抗HBV核苷酸类似物在慢性丁型肝炎(CDH)中的作用尚未得到充分研究。
对我院就诊的HIV阳性CDH患者进行识别并进行纵向研究。每年评估血清HBV DNA、HDV RNA和HIV RNA、治疗方案以及生化和血清学标志物。在最后2年通过瞬时弹性成像测量肝纤维化。
识别出16例患者并接受抗HBV治疗(中位时间6.1年)。大多数为男性,既往有静脉吸毒史。中位基线为:HDV RNA 7 log10拷贝/毫升,HIV RNA 1.7 log10拷贝/毫升,HBV DNA 1.1 log10国际单位/毫升,丙氨酸氨基转移酶(ALT)98国际单位/毫升。HDV RNA与HBV DNA(r = 0.226,P = 0.015)、天冬氨酸氨基转移酶(r = 0.430,P < 0.0001)、ALT(r = 0.441,P < 0.0001)和乙肝表面抗原(HBsAg)(r = 0.557,P < 0.0001)之间存在显著相关性。总体而言,13例患者的HDV病毒血症和ALT水平降低,其中3例HDV RNA检测不到且ALT水平正常。
使用强效核苷酸类似物进行成功抗HBV治疗的患者似乎间接受益于HDV复制的抑制,尽管效率不高。假设只有在实现HBV共价闭合环状DNA或HBsAg降低时,血清HDV RNA才可能出现显著且持续的降低,这可能需要长期成功进行抗HBV治疗。据我们所知,这是强效抗HBV核苷酸类似物疗法在CDH中获益的首个证据。