Hepatitis D – how is the fight against this foe going?
Hepatitis D – how is the fight against this foe going?
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DOI：
10.1080/17512433.2019.1577135
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发表时间：
2019-02
影响因子：
4.4
通讯作者：
A. Loglio;S. Segato;P. Lampertico
中科院分区：
文献类型：
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作者：
A. Loglio;S. Segato;P. Lampertico
丁型肝炎病毒（HDV）是一种小缺陷RNA病毒，只能在与B型肝炎病毒（HBV）共存的个体中繁殖：需要HBV表面抗原（HBsAg）的存在来包裹病毒核糖核蛋白复合物（RNP：小和大-HDV抗原，以及基因组RNA）并完成病毒体组装。在全球2.5亿HBV慢性携带者中，约有1500万至2000万受试者有HDV感染的证据，估计HDV血清阳性率为5- 7%，尽管根据地理来源存在相当大的差异[1]。慢性HDV肝炎患者通常比HBV单一感染者更快进展为肝硬化（每年4%）、肝失代偿、肝细胞癌发作和更高的死亡率。目前，干扰素治疗可以减缓疾病的进展。然而，它仅对20%的患者有效，并且具有显著的副作用。因此，他们中的许多人在年轻时就成为肝移植的候选人。然而，新的疗法，如Lonafarnib，Myrcludex-B，干扰素Lambda和REP 2139 Ca，最近已经在临床前，I期和II期研究中进行了测试，显示出有希望的病毒学和生化结果。前两种药物将于2019年进入注册试验。本文综述了这些新化合物的有效性和安全性，主要是对HBeAg阴性人群进行的。
Hepatitis delta virus (HDV) is a small defective RNA virus that can propagate only in an individual with coexistent hepatitis B virus (HBV): the presence of HBV surface antigen (HBsAg) is required to envelop the viral ribonucleoprotein complex (RNP: small and large-HDV antigen, and genomic RNA) and complete the virion assembly. Approximately 15–20 million subjects have evidence of HDV infection out of the 250 million HBV chronic carriers worldwide, with an estimated HDV seroprevalence of 5–7%, although with a considerable variation according to geographical origins [1]. Patients with chronic HDV hepatitis typically show a more rapid progression to cirrhosis (4% per year), liver decompensation, hepatocellular carcinoma onset, and higher mortality than HBV-monoinfected subjects. Currently, the disease’s progression can be slowed down by interferon therapy. However, it is effective in only 20% of the patients and has significant side effects. Therefore, many of them are candidates to liver transplantation at young age. However, new therapies, such as Lonafarnib, Myrcludex-B, Interferon Lambda, and REP2139Ca, have recently been tested in preclinical, phase I and II studies, showing promising virological and biochemical results. The first two drugs will enter registration trials in 2019. This review summarizes the efficacy and safety of these new compounds, mainly conducted on HBeAg-negative population.