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Hepatic granulomas following liver transplantation: A retrospective survey, and analysis of possible microbiological
Anisoara Iordache1, Kurt Fuursted2, Charlotte Vestrup Rift1
1Department of Pathology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Liver granulomas are common in liver transplant biopsies, often appearing in the first six months post-transplant, particularly in patients with autoimmune liver disease and acute cellular rejection. No infectious agents or distinct microbiome were identified as causes.
Area of Science:
- Hepatology
- Transplantation Immunology
- Pathology
Background:
- Liver granulomas present diagnostic challenges, with limited data on their prevalence and causes in liver transplant recipients.
- Understanding granuloma etiology in this population is crucial for optimizing patient management.
Approach:
- Examined liver biopsies from 217 liver transplant patients between 2011 and 2017.
- Assessed histomorphological features, clinicopathological data, and utilized next-generation sequencing (NGS) for pathogen detection in granuloma-containing biopsies.
Key Points:
- Granulomas were identified in 45.2% of patients (32.8% of biopsies), predominantly as parenchymal epithelioid granulomas.
- Granulomas frequently co-occurred with acute cellular rejection (ACR) and were common in patients transplanted for autoimmune-related liver disease (AILD).
- The highest incidence of granulomas was observed within the first six months post-transplantation.
Conclusions:
- Liver allograft biopsies frequently show granulomas, mainly in the parenchyma, especially in the early post-transplant phase.
- Granulomas are associated with AILD and ACR episodes, but no specific infectious agent or consistent microbiome was identified.
- The findings highlight the non-infectious nature of most granulomas in liver transplant recipients.
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