Marcucci Fabrizio, Spada Enea, Mele Alfonso, Caserta Carmelo Antonio, Pulsoni Alessandro
Am J Blood Res. 2012;2(1):18-28. Epub 2012 Jan 1.
Epidemiological studies performed over the last decade have demonstrated a positive association between persistent, hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (NHL), with HBV-infected patients having a 2-3-fold higher risk to develop NHL than non-infected patients. Moreover, there is evidence that also occult HBV infection (HBsAg-negative, HBV DNA-positive) associates with NHL. An association with HBV infection may exist also for other hematological malignancies, but available evidence is much less persuasive than for NHL. In this review article we will discuss available results on the association between HBsAg-positive HBV infection and NHL, as well as the significance of other serological markers of HBV infection in these subjects. We will also discuss the possible etiopathogenic role of HBV, and propose a multifactorial model for lymphomagenesis. Experimental evidence for multifactorial etiopathogenesis has been obtained in recent years for HBV-associated hepatocellular carcinoma (HCC), and we suggest that a similar model may apply to HBV-associated lymphoma as well. Eventually, we will also address some unresolved questions. Two of these are of particular relevance. First, do HBV-positive NHL patients show regression of their hematologic malignancy upon antiviral therapy? A positive answer would represent a direct demonstration of the necessary etiological role of the virus in the development of NHL, as has been shown previously for HCV-associated lymphomas. Second, if HBV plays a necessary role in lymphomagenesis, then expansion of HBV vaccination is expected to reduce the number of incident NHL cases, even though this effect might become evident only after a long time interval. Studies in those countries which have introduced universal HBV vaccination about two decades ago, like Italy, may soon provide results on this important point.
过去十年进行的流行病学研究表明，持续性乙肝表面抗原（HBsAg）阳性的乙型肝炎病毒（HBV）感染与B细胞非霍奇金淋巴瘤（NHL）之间存在正相关，HBV感染患者发生NHL的风险比未感染患者高2至3倍。此外，有证据表明隐匿性HBV感染（HBsAg阴性、HBV DNA阳性）也与NHL有关。其他血液系统恶性肿瘤可能也与HBV感染有关，但现有证据的说服力远不如NHL。在这篇综述文章中，我们将讨论HBsAg阳性HBV感染与NHL之间关联的现有结果，以及这些患者中其他HBV感染血清学标志物的意义。我们还将讨论HBV可能的病因致病作用，并提出淋巴瘤发生的多因素模型。近年来，对于HBV相关肝细胞癌（HCC）已经获得了多因素病因发病机制的实验证据，我们认为类似的模型也可能适用于HBV相关淋巴瘤。最后，我们还将探讨一些未解决的问题。其中两个问题尤为相关。第一，HBV阳性的NHL患者在接受抗病毒治疗后血液系统恶性肿瘤是否会消退？肯定的答案将直接证明病毒在NHL发生中具有必要的病因学作用，正如先前在HCV相关淋巴瘤中所显示的那样。第二，如果HBV在淋巴瘤发生中起必要作用，那么扩大HBV疫苗接种有望减少NHL新发病例的数量，尽管这种效果可能要经过很长一段时间才会显现。在大约二十年前就已推行普遍HBV疫苗接种的国家，如意大利，所开展的研究可能很快会在这一重要问题上给出结果。
