Journal of Pathology and Translational Medicine

Review

Post-transplant liver biopsies: a concise and practical approach for beginners: Mohamad Besher Ourfali, David Hirsch, Marianna Scranton, Tony El Jabbour; J Pathol Transl Med. 2025;59(1):1-10. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.15

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Abstract PDF: Exposure to post-transplant liver biopsies varies among pathology residencies and largely depends on the institution's training program, particularly if the hospital has a liver transplant program. The interpretation of biopsies from transplanted livers presents its own set of challenges, even for those with a solid understanding of non-transplant medical liver biopsies. In this review, we aim to provide a succinct, step-by-step approach to help you interpret liver transplant biopsies. This article may be beneficial for residents interested in liver pathology, gastrointestinal and liver pathology fellows in the early stages of training, clinical gastroenterology and hepatology fellows, hepatologists and general pathologists who are curious about this niche.

Original Articles

Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation: Haeyon Cho, Jin-Oh Choi, Eun-Seok Jeon, Jung-Sun Kim; J Pathol Transl Med. 2019;53(1):50-56. Published online December 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.30

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Background
The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients.
Methods
A total of 1190EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions,acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy wasdiagnosed by computed tomography coronary angiography. Clinical information, including thepatients’ survival was retrieved by a review of medical records.
Results
Eighty-eight patients(75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellularrejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patientsdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesionsfrom transplantation was longer than that of acute cellular rejections. We found a significant associationbetween Quilty lesions and cardiac allograft vasculopathy. No significant relationship wasfound between Quilty lesions and the patients’ survival.
Conclusions
Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection.

Citations

Citations to this article as recorded by

The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species
Kevin C. Bermea, Nicolas Kostelecky, Sylvie T. Rousseau, Chieh-Yu Lin, Luigi Adamo
Frontiers in Immunology.2022;[Epub] CrossRef
Examination of tracheal allografts after long-term survival in dogs
Tao Lu, Yiwei Huang, Yulei Qiao, Yongxing Zhang, Yu Liu
European Journal of Cardio-Thoracic Surgery.2021; 59(1): 155. CrossRef
Essentials in the diagnosis of postoperative myocardial lesions similar to or unrelated to rejection in heart transplant
Costel Dumitru, Ancuta Zazgyva, Adriana Habor, Ovidiu Cotoi, Horațiu Suciu, Carmen Cotrutz, Bogdan Grecu, Ileana Anca Sin
Revista Romana de Medicina de Laborator.2021; 29(3): 307. CrossRef
Clinical outcome of donor heart with prolonged cold ischemic time: A single‐center study
Fazal Shafiq, Yixuan Wang, Geng Li, Zongtao Liu, Fei Li, Ying Zhou, Li Xu, Xingjian Hu, Nianguo Dong
Journal of Cardiac Surgery.2020; 35(2): 397. CrossRef
The XVth Banff Conference on Allograft Pathology the Banff Workshop Heart Report: Improving the diagnostic yield from endomyocardial biopsies and Quilty effect revisited
Jean-Paul Duong Van Huyen, Marny Fedrigo, Gregory A. Fishbein, Ornella Leone, Desley Neil, Charles Marboe, Eliot Peyster, Jan von der Thüsen, Alexandre Loupy, Michael Mengel, Monica P. Revelo, Benjamin Adam, Patrick Bruneval, Annalisa Angelini, Dylan V. M
American Journal of Transplantation.2020; 20(12): 3308. CrossRef

Characterization of Histopathological Features that Differentiate Hepatitis B Virus Infection from Acute Cellular Rejection.: Dong Eun Song, Dong Hwan Jung, Shin Hwang, Bong Hee Park, Eunsil Yu; Korean J Pathol. 2009;43(6):535-541.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.535

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Abstract PDF

BACKGROUND
Differentiation of viral hepatitis from acute cellular rejection (ACR) after liver transplantation can be difficult because of overlapping histological features. Here we investigated clinicopathologic characteristics of 311 liver allograft biopsies and searched for characteristic histopathological features that would facilitate the differential diagnosis between hepatitis B virus (HBV) infection and ACR. METHODS: A retrospective clinicopathologic examination of 311 liver allograft biopsies consisting of clinically proven ACR or HBV infection was performed. Immunohistochemical staining for HBcAg and HBsAg was done for 64 allograft biopsies showing HBV infection. RESULTS: Moderate to severe bile duct damage, diffuse centrilobular necrosis and centrilobular inflammation (p<0.000, for each) were more frequently observed in cases of ACR, whereas diffuse acidophilic bodies and spotty necrosis (p<0.000, for each) were more prevalent in cases of HBV infection. Immunopositivity for HBcAg (n=60, 93.8%) was higher than that for HBsAg (n=14, 21.9%) CONCLUSIONS: The presence of moderate to severe bile duct damage, diffuse centrilobular necrosis and centrilobular inflammation was a characteristic feature of ACR, whereas diffuse distribution of acidophilic bodies or spotty necrosis was the only characteristic feature of HBV infection. HBcAg was a more sensitive immunohistochemical marker than HBsAg for detecting HBV infection in liver allograft biopsies.

Citations

Citations to this article as recorded by

Analysis of S Gene Mutation of the Hepatitis B Virus in Adult Liver Transplant Recipients Showing Resistance to Hepatitis B Immunoglobulin Therapy
G.-C. Park, S. Hwang, C.-S. Ahn, K.-H. Kim, D.-B. Moon, T.-Y. Ha, G.-W. Song, D.-H. Jung, Y.W. Shin, S.-H. Kim, K.-H. Chang, J.-M. Namgoong, C.-S. Park, H.-W. Park, Y.-H. Park, S.-H. Kang, B.-H. Jung, S.-G. Lee
Transplantation Proceedings.2013; 45(8): 3047. CrossRef
Posttransplantation prophylaxis with primary high-dose hepatitis B immunoglobulin monotherapy and complementary preemptive antiviral add-on a
Shin Hwang, Chul-Soo Ahn, Gi-Won Song, Ki-Hun Kim, Deok-Bog Moon, Heung-Bum Oh, Young-Suk Lim, Han Chu Lee, Tae-Yong Ha, Dong-Hwan Jung, Young-Hwa Chung, Sung-Gyu Lee
Liver Transplantation.2011; 17(4): 456. CrossRef
Posttransplantation Prophylaxis with Primary High-dose Hepatitis B Immunoglobulin Monotherapy and Complementary Preemptive Antiviral Add-on. Liver Transpl 2011;17:456-465
Dong-Hwan Jung, Shin Hwang
The Korean Journal of Gastroenterology.2011; 57(5): 330. CrossRef

Pathological Analysis of Post-Transplantation Endomyocardial Biopsies.: Jaegul Chung, Soonae Oak, Gheeyoung Choe, Gyungyub Gong, Jooryung Huh, Eunsil Yu, Inchul Lee, Meong Gun Song, Kwang Hyun Sohn, Jae Joong Kim, Jong Goo Lee; Korean J Pathol. 1995;29(4):431-441.

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Abstract PDF: Heart transplantation was first performed in 1967. It is now regarded as a well-established treatment modality for end-stage cardiac diseases. Once the transplantation is performed, endomyocardial biopsy(EMB) is the examination of choice in monitoring the transplanted heart. We analyzed the pathological findings of follow-up EMB of 6 heart transplant patients. All patients have been suffered from severe heart failure. Four patients were adult male and two were adult females. All the hearts, except for one, displayed characteristic features of dilated cardiomyopathy. The remaining heart was diagnosed as having giant cell myocarditis. Post-transplantion EMBs were performed according to the protocol and standard cardiac biopsy grading of ISHT (1990). The standards were applied for grading of cellular rejection. In five patients, there were one or two episodes of biopsy proven acute rejection, grade II or IIIA without any clinical symptoms of rejection. Immediate "pulse therapy" was performed and follow-up biopsies were done. All episodes of rejection were cleared in subsequent biopsies. All patients are doing well without evidence of cardiac problem. The postoperative monitoring of acute rejection is critical since clinical signs of rejection are usually absent. At present, EMB is regarded as the most reliable method for diagnosis and grading of acute rejection and is an efficient guide to the monitoring of the cardiac recipients. Our experience of post-transplantation EMB corresponds with previously published reports.

Pathologic Analysis of Endomyocardial Biopsies in Heart Transplantation.: Mee Hye Oh, Jeong Wook Seo, Kook Yang Park, Young Tak Lee, Yoon Seop Jeong, Suk Keun Hong, Joon Ryang Rho, Byung Hee Oh, Sung Sook Kim; Korean J Pathol. 1998;32(2):104-114.

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Abstract PDF: Endomyocardial biopsy (EMB) is a valuable diagnostic procedure for the surveillance of cardiac allograft rejection. Interpretation of individual cases is still problematic due to variations of findings for grading of rejection and other associated lesions. We reevaluated an experience on endomyocardial biopsies to develop better diagnostic criteria for rejection and other complications. Immunohistochemical studies against cytokines were performed to assess the usefulness of the method for the diagnosis or researches. A total of 249 EMBs taken from 33 cardiac allograft recipients were reviewed. There were 25 males and 8 females. Dilated cardiomyopathy was present (24 cases) and valvular heart disease (4 cases), restrictive cardiomyopathy (3 cases) were also common conditions. We applied the grading system of the International Society for Heart Transplantation (ISHT) for the assessment of acute cellular rejection. Grades of 0, 1A, 1B, 2, 3A and 3B were 39.0%, 28.1%, 11.2%, 11.5%, 12.4% and 1.6% respectively, but 3.2% were inadequate. Thirty five episodes of grade 3A or 3B were present in 17 patients. The response to therapy was assessed using a next follow up biopsy, which revealed resolving or resolved rejection in 85% of patients. The intensity of immunohistochemical stains for IL-6 and TNF-alpha was increased in proportion to the histologic grade but Quilty lesion and cardiomyopathy also showed a positive reaction. The other pathologic findings were ischemic change, previous biopsy site, interstitial edema and fibrosis, and Quilty lesion. These findings showed usefulness of endomyocardial biopsy not only for the evaluation of cardiac allograft rejection but also for the diagnosis of associated cardiac lesions. Immunohistochemical study of the cytokines was related to the degree of inflammation rather than degree of rejection.

A Clinicopathological Study of Posttransplant Liver Biopsy.: Na Rae Kim, Dae Su Kim, Young Lyun Oh, Mi Kyung Kim, Young Hyeh Ko; Korean J Pathol. 1999;33(3):169-178.

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Abstract PDF: Liver biopsies are used routinely in the assessment of graft dysfunction following liver transplantation and generally considered to be the most reliable method for the diagnosis of posttransplant complications with overlapping clinical and laboratory findings. To investigate posttransplant complications causing graft dysfunction and usefulness of liver biopsy, we analysed clinicopathologic features of 65 posttransplant liver biopsies, 2 autopsies and an explanted liver, taken from 20 patients. The frequencies of posttransplant complications were acute cellular rejection in 9 patients (45%), postoperative infection in 11 patients (55%), of which cytomegalovirus (CMV) infection and systemic invasive aspergillosis with candidiasis occured in 10 patients (50%) and 1 patient (5%), respectively. Remainders were hepatic arterial thrombosis in two (10%), primary graft dysfunction due to fatty donor liver in one (5%), and posttransplant lymphoproliferative disorder (PTLD) in two (10%). There were no chronic rejection or recurrent disease. Postoperative mortality was 25%. Histologic grade by Banff schema was well correlated with clinical parameters associated with unfavorable short term prognosis. CMV infection was associated with acute cellular rejection in 6 out of 10 patients (60%). Immunohistochemical staining for CMV was more sensitive method than CMV in situ hybridization or histologic detection of viral inclusion on tissue section. It was unique that one case of PTLD developed under the circumstances of the lowest dosage of immunosuppression and took grave outcome. Based on these results, we concluded that clinicopathologic correlation with integration of all the clinical and laboratory findings is necessary in the interpretation of accurate and early diagnosis of posttransplant liver biopsies. The interrelationship between chronic rejection and CMV infection as well as pathogenetic factors of PTLD remains to be clarified through further ongoing observation.

Case Report

Disseminated Systemic Candidiasis and Aspergillosis in a Liver Transplant Patient: An Autopsy Report.: Na Rae Kim, Dae Su Kim, Young Hyeh Ko, Sung Joo Kim; Korean J Pathol. 2002;36(5):348-352.

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Abstract PDF: Postoperative complications of liver transplantation include rejection, infection, hepatic vascular thrombus, and primary graft failure, etc. Among them, fungal infection shows nonspecific clinical symptoms and overlapping laboratory findings with variable etiologies causing post-transplant hepatic dysfunction. Therefore, early diagnosis of fungal infection is not easy. Here, we report an autopsy case of disseminated candidiasis and aspergillosis in a liver transplant patient. The case was at first misinterpreted as acute cellular rejection on biopsy because the histology of predominantly cellular infiltration, ductulitis and endothelialitis were similar to those of acute cellular rejection. On autopsy, the liver, lung and kidney showed multifocal hemorrhagic infarcts due to intra-arterial fungal emboli, which were composed mostly of candida species and a minor fraction of aspergillus. Fungal thrombi invading portal vein, intrahepatic arterioles with subsequent coagulation necrosis, venulitis and ductulitis were ascribed to the misdiagnosis on biopsies. It is unusual that systemic candidiasis, unlike aspergillosis, involves large arteries.

Original Articles

The Expression of C4d and HLA-DR in Renal Allografts with the Histologic Features of Antibody-Mediated Rejection.: Young Soo Song, Moon Hyang Park; Korean J Pathol. 2008;42(5):260-269.

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Abstract PDF: BACKGROUND
Deposition of C4d along the peritubular capillaries is generally associated with an antibody-mediated response. We evaluated, with performing C4d immunostaining, the diagnostic accuracy of the cases that were previously diagnosed as antibody-mediated rejection (ABMR) when based only on the histologic findings, and we examined possible correlation of C4d with HLA-DR.
METHODS
Forty-five renal transplantation biopsies, which showed ABMR-like histology, were obtained. The expressions of C4d and HLA-DR in the transplant rejection cases were investigated using immunofluorescent and/or immunohistochemical staining. RESULTS: There were 14 discordant cases among a total of 45 cases when C4d was used as a diagnostic marker and the original slides were reviewed. These total cases consisted of the C4d negative cases in two cases of hyperacute rejection and all the cases of ABMR and ABMR with chronic/sclerosing allograft nephropathy (CAN) and two C4d positive cases (one each of acute cellular rejection (ACR) and CAN according to their original diagnosis) and all these cases were then revised according to Banff 07. The expression of HLA-DR tended to be correlated with the log-transformed duration of grafts until three years after the transplantation. CONCLUSION: This study demonstrates that C4d together with the histologic findings should be used for making the diagnosis of ABMR. The tubular HLA-DR expression over time should be studied to further understand the mechanism of graft rejection.

Immunohistochemical Profile of Acute Cellular Rejection in Renal Allograft.: Jongha Park, Seung Woon Byun, Eunsil Yu, Su Kil Park, Duck Jong Han, Yong Mee Cho; Korean J Pathol. 2007;41(1):15-20.

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Abstract PDF: BACKGROUND
We wanted to find an adjunctive marker(s) in renal allograft biopsies for predicting acute cellular rejection (ACR), and so the expression patterns of immune-related molecules were compared between ACR, borderline ACR and non-ACR cases.
METHODS
The expression patterns of Fas ligand (FasL), HLA-DR, granzyme B, caspase-3, CD56, interferon stimulated growth factor-3 (ISGF-3), and CD53 were assessed via immunohistochemical study in 75 allograft biopsies from patients with ACR (n=19), borderline ACR (n=22), and non-ACR (n=34).
RESULTS
Compared to those of the non-ACR group, the ACR group revealed an elevated number of FasL positive interstitial inflammatory cells, HLA-DR positive tubular inflammatory cells, cytoplasmic caspase-3 positive tubular epithelial cells, granzyme B positive interstitial mononuclear inflammatory cells and CD53 positive interstitial inflammatory cells. The expression patterns of the borderline ACR group were similar to those of non-ACR group, except for the intensity of FasL in the tubular epithelial cells.
CONCLUSIONS
Immunohistochemical investigations of the adjunctive markers FasL, HLA-DR, granzyme B, caspase-3 and CD56 can be useful for making the diagnosis of ACR.

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