Background

Therapy of chronic hepatitis D (CHD) is still based on interferon alpha (IFNα), introduced in clinical practice 30 years ago: results are modest and better therapies are an urgent medical need.

Aims

This article provides a critical overview of the new therapies under investigation for CHD.

Sources

Review of the recently published medical literature.

Content

New therapeutic efforts aim to deprive the hepatitis D virus (HDV) of functions provided to its life cycle by the hepatitis B Virus (HBV) or by the host. Three therapeutic strategies are in evaluation: a) Myrcludex B, a myristolated lipopeptide of the pre-S1 domain of the HBsAg that blocks the entry of the HDV into hepatocyes and controls infection by preventing the spreading of the virus to liver cells not infected by the HBV; b) Lonafarnib, an inhibitor of a host farnesyl-transferase that hinders morphogenesis of the HDV by preventing the farnesylation of the large HD-antigen, necessary for virion assembly; c) REP 2139, a nucleic acid polymer that prevents export of the mature HDV by the presumed inhibition of the synthesis of subviral HBsAg particles with which the virion is coated. Myrcludex B and Lonafarnib increase therapeutic efficacy in combination with Peg-IFNα. In a pilot study, REP 2139 in combination with Peg-IFNα induced the clearance of serum HDV RNA and of the HBsAg in about half of 12 treated patients.

Implications

Long-term therapies with either Myrcludex B or Lonafarnib in combination with Peg-IFNα are required to achieve clinical control of CHD. However, with prolonged therapies tolerance becomes a problem; studies are on the way to determine whether Peg-IFN lambda may be better tolerated that Peg-IFNα. The promising preliminary data of REP 2139 in combination with Peg-IFNα await confirmation of the original pilot study.

中文翻译：

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丁型肝炎的治疗：未满足的医疗需求。

背景

慢性D型肝炎（CHD）的治疗仍基于30年前临床实践中引入的干扰素α（IFNα）：结果适中，更好的治疗是迫切的医学需求。

目的

本文提供了正在研究的冠心病新疗法的重要概述。

资料来源

回顾最近出版的医学文献。

内容

新的治疗方法旨在剥夺乙型肝炎病毒（HBV）或宿主为其生命周期提供的功能。评估三种治疗策略：a）Myrcludex B，HBsAg前S1结构域的豆蔻酸酯化脂肽，可阻止HDV进入肝细胞，并通过防止病毒传播到未感染该病毒的肝细胞来控制感染。乙肝病毒 b）Lonafarnib，一种宿主法呢基转移酶的抑制剂，通过阻止病毒体组装所必需的大的HD抗原的法呢基化而阻碍HDV的形态发生；c）REP 2139，一种核酸聚合物，通过推测抑制病毒颗粒包被的亚病毒HBsAg颗粒的合成而阻止成熟HDV的输出。Myrcludex B和Lonafarnib与Peg-IFNα结合可提高治疗效果。在一项前期研究中，REP 2139与Peg-IFNα组合可在约12名接受治疗的患者中诱导血清HDV RNA和HBsAg的清除。

含义

需要长期应用Myrcludex B或Lonafarnib联合Peg-IFNα进行治疗，以实现CHD的临床控制。然而，随着疗法的延长，耐受性成为一个问题。正在进行研究以确定Peg-IFN lambda是否比Peg-IFNα更能耐受。REP 2139与Peg-IFNα结合的有希望的初步数据有待原始试验研究的证实。