Iordache Anisoara, Fuursted Kurt, Rift Charlotte Vestrup, Rasmussen Allan, Willemoe Gro Linno, Hasselby Jane Preuss
Department of Pathology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Department of Microbiology and Infection Control, Reference Laboratory, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Pathol Res Pract. 2024 Mar;255:155201. doi: 10.1016/j.prp.2024.155201. Epub 2024 Feb 9.
Liver granulomas have always been a diagnostic challenge for pathologists. They have been described in up to 15% of liver biopsies and can also be seen in liver allograft biopsy specimens, but there is a paucity of information regarding the prevalence and associated etiologic factors of granulomas in liver transplanted patients. The aim of this study is to shed light on the etiology of liver granulomas.
Liver biopsies from liver transplanted patients, in the period from 01.01.2011 - 01.05.2017, were examined. We registered the histo-morphological characteristics and clinicopathological data of all biopsies and performed next-generation sequencing (NGS) to detect possible pathogens (bacteria, fungi, and parasites) in the biopsies containing granulomas.
We reviewed a total of 400 liver biopsies from 217 liver transplant patients. Of these, 131 liver biopsies (32.8%) from 98 patients (45.2%) revealed granulomas. Most were epithelioid granulomas located parenchymal and were detected in 115 (87.7%) biopsies. We also identified 10 cases (7.6%) with both lobular and portal granulomas and six biopsies (4.5%) with portal granulomas alone. In 54 biopsies (41.2%), granulomas were found in biopsies with acute cellular rejection (ACR). Fifty (51%) patients with granulomas underwent liver transplantation for autoimmune-related end-stage liver disease (AILD). The granulomas were found most frequently in the first six months after transplantation, where patients also more often were biopsied. NGS analysis did not reveal any potential infectious agent, and no significant differences were observed in the microbiological diversity (microbiome) between clinical- and granuloma characteristics concerning bacteria, fungi, and parasites.
Our study confirmed that granulomas are frequently seen in liver allograft biopsy specimens, and most often localized in the parenchyma, occurring in the first post-transplant period in patients with AILD, and often seen simultaneously with episodes of ACR. Neither a specific microbiological etiological agent nor a consistent microbiome was detected in any case.
肝脏肉芽肿一直是病理学家面临的诊断挑战。在高达15%的肝脏活检中都有其描述，在肝移植活检标本中也可见到，但关于肝移植患者肉芽肿的患病率及相关病因的信息却很少。本研究旨在阐明肝脏肉芽肿的病因。
对2011年1月1日至2017年5月1日期间肝移植患者的肝脏活检进行检查。我们记录了所有活检的组织形态学特征和临床病理数据，并对含有肉芽肿的活检组织进行二代测序（NGS）以检测可能的病原体（细菌、真菌和寄生虫）。
我们回顾了217例肝移植患者的共400份肝脏活检。其中，98例患者（45.2%）的131份肝脏活检（32.8%）显示有肉芽肿。大多数为上皮样肉芽肿，位于实质内，在115份活检（87.7%）中被检测到。我们还发现10例（7.6%）既有小叶性肉芽肿又有门管区肉芽肿，6份活检（4.5%）仅有门管区肉芽肿。在54份活检（41.2%）中，肉芽肿在伴有急性细胞排斥反应（ACR）的活检中被发现。50例（51%）有肉芽肿的患者因自身免疫相关终末期肝病（AILD）接受肝移植。肉芽肿最常在移植后的前六个月被发现，此期间患者也更常接受活检。NGS分析未发现任何潜在的感染因子，在细菌、真菌和寄生虫的临床特征与肉芽肿特征之间的微生物多样性（微生物群）方面未观察到显著差异。
我们的研究证实，肉芽肿在肝移植活检标本中很常见，最常位于实质内，发生在AILD患者移植后的最初阶段，且常与ACR发作同时出现。在任何病例中均未检测到特定的微生物病因或一致的微生物群。
