Potenza Leonardo, Luppi Mario, Barozzi Patrizia, Rossi Giulio, Cocchi Stefania, Codeluppi Mauro, Pecorari Monica, Masetti Michele, Di Benedetto Fabrizio, Gennari William, Portolani Marinella, Gerunda Giorgio Enrico, Lazzarotto Tiziana, Landini Maria Paola, Schulz Thomas F, Torelli Giuseppe, Guaraldi Giovanni
Department of Oncology and Hematology, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy.
N Engl J Med. 2008 Aug 7;359(6):593-602. doi: 10.1056/NEJMoa074479.
Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis.
多核巨细胞性肝炎是一种罕见但严重的肝炎形式,与自身免疫性疾病、药物反应和病毒感染有关。我们采用血清学、分子学和免疫组化方法,对一名肝移植受者发生的多核巨细胞性肝炎病例进行感染病因排查。该受者潜伏感染人疱疹病毒6 B型(HHV - 6B),所接受的器官来自潜伏感染A型(HHV - 病6A)的供者。在疾病发作时,使用两种不同的聚合酶链反应(PCR)检测方法,在血浆、受影响的肝组织以及单个经显微操作的多核巨细胞中检测到HHV - 6A(而非HHV - 6B)DNA,表明患者存在活跃的HHV - 6A感染。仅在肝多核巨细胞中证实了HHV - 6A特异性早期蛋白p41/38的表达,而未发现HHV - 6B特异性晚期蛋白p101的表达,且不存在其他感染病原体。在患者的系列随访样本中记录到相同的HHV - 6A活跃感染标志物,且仅在多核巨细胞性肝炎消退时才消失。在患者的相同随访样本中未鉴定出HHV - 6B DNA或晚期蛋白。因此,HHV - 6A可能是多核巨细胞性肝炎的病因。