Smedile A, Rizzetto M, Gerin J L
Department of Gastroenterology, Ospedale Molinette, Italy.
Prog Liver Dis. 1994;12:157-75.
Studies over the last decade have defined the natural history and diagnostic features of hepatitis D. Whereas hepatitis D encompasses a wide spectrum of clinical manifestations, patients usually have severe and progressive liver disease. In areas of high endemicity such as Italy, hepatitis D accounts for a significant proportion of requests for liver transplantation. Research interest is now focused on the underlying mechanisms of HDV pathogenesis and identification of the specific interactions of HDV/HBV/host that influence the clinical outcome. Much has been learned about the virology of HDV and its interactions with its helper, HBV. However, little is known about the host response to HDV infection and whether certain immune responses to HDV gene products can modulate the disease course, although there has been some evidence in an animal model that this might be the case. The unique characteristics of HDV replication, eg, autocatalytic self-cleavage and editing of the viral RNA, may influence the disease course and the heterogeneity of HDV genome sequence found in various geographic settings may in part account for the spectrum of disease outcomes by influencing the efficiency of any number of complex interactions. Fortunately, in vitro and in vivo experimental systems are available to address many of these issues and, indeed, further research may identify specific and novel targets for therapeutic intervention. Current medical therapy for hepatitis D is unsatisfactory. The only drug of proven benefit, recombinant interferon, brings relief to only a small proportion of hepatitis D patients. Other antiviral drugs have failed in clinical trials, although studies with some drugs are currently in progress. Fortunately, liver transplantation provides a valid option, because HDV reinfection of the graft occurs much less frequently than does HBV reinfection of HBV transplants and can be adequately prevented by the administration of anti-HBs immunoglobulin. Because of the critical contribution of HBV to the life cycle of HDV, universal immunization against HBV infection represents the ultimate solution for the eradication of hepatitis D. Mass vaccination for HBV and other public health measures for the control of blood-borne pathogens have already resulted in a dramatic decrease in hepatitis D in Italy.
过去十年的研究已经明确了丁型肝炎的自然病史和诊断特征。虽然丁型肝炎涵盖了广泛的临床表现，但患者通常患有严重且进行性的肝病。在意大利等高流行地区，丁型肝炎占肝移植需求的很大比例。目前研究兴趣集中在丁型肝炎病毒发病机制的潜在机制以及确定影响临床结局的HDV/HBV/宿主之间的特定相互作用。关于HDV病毒学及其与辅助病毒HBV的相互作用，人们已经了解了很多。然而，对于宿主对HDV感染的反应以及对HDV基因产物的某些免疫反应是否能调节疾病进程知之甚少，尽管在动物模型中有一些证据表明可能如此。HDV复制的独特特征，例如病毒RNA的自催化自我切割和编辑，可能会影响疾病进程，并且在不同地理环境中发现的HDV基因组序列的异质性可能部分解释了通过影响众多复杂相互作用的效率而导致的疾病结局谱。幸运的是，有体外和体内实验系统可用于解决许多这些问题，实际上，进一步的研究可能会确定治疗干预的特定和新靶点。目前针对丁型肝炎的药物治疗并不令人满意。唯一被证明有益的药物重组干扰素仅能使一小部分丁型肝炎患者病情缓解。其他抗病毒药物在临床试验中失败了，尽管目前一些药物的研究正在进行中。幸运的是，肝移植提供了一个有效的选择，因为与HBV移植中HBV再感染相比，HDV在移植物中的再感染发生频率要低得多，并且可以通过给予抗-HBs免疫球蛋白充分预防。由于HBV对HDV生命周期的关键作用，普遍接种HBV疫苗是根除丁型肝炎的最终解决方案。在意大利，针对HBV的大规模疫苗接种以及其他控制血源性病原体的公共卫生措施已经导致丁型肝炎显著减少。
