Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Center for Basic and Clinical Immunology Research, WAO Center of Excellence, University of Naples Federico II, Naples, Italy.
Front Immunol. 2020 Feb 28;11:338. doi: 10.3389/fimmu.2020.00338. eCollection 2020.
Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency (PID) in adulthood and is characterized by severe reduction of immunoglobulin serum levels and impaired antibody production in response to vaccines and pathogens. Beyond the susceptibility to infections, CVID encompasses a wide spectrum of clinical manifestations related to a complex immune dysregulation that also affects liver. Although about 50% CVID patients present persistently deranged liver function, burden, and nature of liver involvement have not been systematically investigated in most cohort studies published in the last decades. Therefore, the prevalence of liver disease in CVID widely varies depending on the study design and the sampling criteria. This review seeks to summarize the evidence about the most relevant causes of liver involvement in CVID, including nodular regenerative hyperplasia (NRH), infections and malignancies. We also describe the clinical features of liver disease in some monogenic forms of PID included in the clinical spectrum of CVID as ICOS, NFKB1, NFKB2, CTLA-4, PI3Kδ pathway, ADA2, and IL21-R genetic defects. Finally, we discuss the clinical applications of the various diagnostic tools and the possible therapeutic approaches for the management of liver involvement in the context of CVID.
普通变异性免疫缺陷症（CVID）是成年人中最常见的原发性免疫缺陷症（PID），其特征是血清免疫球蛋白水平严重降低，对疫苗和病原体的抗体产生受损。除了易感染外，CVID 还包括广泛的与复杂免疫失调相关的临床表现，也会影响肝脏。尽管约 50%的 CVID 患者持续存在肝功能异常，但在过去几十年发表的大多数队列研究中，尚未系统研究肝脏受累的负担和性质。因此，CVID 中肝脏疾病的患病率因研究设计和采样标准的不同而有很大差异。本综述旨在总结 CVID 中肝脏受累的最相关原因的证据，包括结节性再生性增生症（NRH）、感染和恶性肿瘤。我们还描述了一些 CVID 临床谱中包含的单基因形式 PID 中肝脏疾病的临床特征，包括 ICOS、NFKB1、NFKB2、CTLA-4、PI3Kδ 通路、ADA2 和 IL21-R 遗传缺陷。最后，我们讨论了在 CVID 背景下管理肝脏受累的各种诊断工具的临床应用和可能的治疗方法。
