Journal of Pathology and Translational Medicine

Case Study

Uncommon granulomatous manifestation in Epstein-Barr virus–positive follicular dendritic cell sarcoma: a case report: Henry Goh Di Shen, Yue Zhang, Wei Qiang Leow; Received July 1, 2024 Accepted September 26, 2024 Published online October 31, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.27 [Epub ahead of print]

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Abstract PDF: Hepatic Epstein-Barr virus–positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) represents a rare form of liver malignancy. The absence of distinct clinical and radiological characteristics, compounded by its rare occurrence, contributes to a challenging diagnosis. Here, we report a case of a 54-year-old Chinese female with a background of chronic hepatitis B virus treated with entecavir and complicated by advanced fibrosis presenting with a liver mass found on her annual surveillance ultrasound. Hepatectomy was performed under clinical suspicion of hepatocellular carcinoma. Immunomorphologic characteristics of the tumor were consistent with EBV+ IFDCS with distinct non-caseating granulomatous inflammation. Our case illustrates the importance of considering EBV+ IFDCS in the differential diagnosis of hepatic inflammatory lesions. Awareness of this entity and its characteristic features is essential for accurately diagnosing and managing this rare neoplasm.

Original Articles

A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy: Kyoungbun Lee, Eun Sun Jung, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2020;54(3):228-236. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.07

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Background
Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis.
Methods
Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system.
Results
Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH.
Conclusions
A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

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Lipid nanoparticle-mediated hepatocyte delivery of siRNA and silibinin in metabolic dysfunction-associated steatotic liver disease
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Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
Gastroenterología y Hepatología.2022; 45(8): 579. CrossRef
Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
Gastroenterología y Hepatología (English Edition).2022; 45(8): 579. CrossRef

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker: Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim; J Pathol Transl Med. 2018;52(5):267-274. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.14

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Abstract PDF

Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

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Analysis of Inflammatory and Thyroid Hormone Levels Based on Hepatitis A and B Virus Immunity Status: Age and Sex Stratification
Hyeokjun Yun, Jae-Sik Jeon, Jae Kyung Kim
Viruses.2024; 16(8): 1329. CrossRef
Ferritin and procalcitonin serve as discriminative inflammatory biomarkers and can predict the prognosis of severe fever with thrombocytopenia syndrome in its early stages
Keping Chen, Huidi Sun, Yu Geng, Chuankun Yang, Chun Shan, Yuxin Chen
Frontiers in Microbiology.2023;[Epub] CrossRef
Evaluation of Serum Ferritin, Procalcitonin, and C-Reactive Protein for the Prediction of Severity and Mortality in Hemorrhagic Fever With Renal Syndrome
Lihe Che, Zedong Wang, Na Du, Liang Li, Yinghua Zhao, Kaiyu Zhang, Quan Liu
Frontiers in Microbiology.2022;[Epub] CrossRef
Hepatocellular adenomas: recent updates
Haeryoung Kim, Young Nyun Park
Journal of Pathology and Translational Medicine.2021; 55(3): 171. CrossRef
A prospective follow-up study of the relationship between high-sensitivity C-reactive protein and primary liver cancer
Sarah Tan Siyin, Tong Liu, Wenqiang Li, Nan Yao, Guoshuai Xu, Jun Qu, Yajun Chen
BMC Cancer.2020;[Epub] CrossRef
CRP Levels in Viral Hepatitis: A Meta-Analysis Study
Sukhpal Singh, Abhishek Bansal, Pardeep Kumar
International Journal of Infection.2020;[Epub] CrossRef

Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence: Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee; J Pathol Transl Med. 2016;50(3):181-189. Published online April 17, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.18

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Abstract PDF

Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.

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Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis
Anja Schollmeier, Mirco Glitscher, Eberhard Hildt
International Journal of Molecular Sciences.2023; 24(5): 4964. CrossRef
Nomogram to predict the prognosis of patients with AFP-negative hepatocellular carcinoma undergoing chemotherapy: A SEER based study
Lei Wang, Jin-Lin Peng, Ji-Zhou Wu
Medicine.2023; 102(13): e33319. CrossRef
Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients
Wei Teng, Yen-Chun Liu, Wen-Juei Jeng, Chien-Wei Su
Cancers.2021; 13(7): 1729. CrossRef
Suppression of hepatitis b virus by a combined activity of CRISPR/Cas9 and HBx proteins
S. A. Brezgin, A. P. Kostyusheva, V. N. Simirsky, E. V. Volchkova, D. S. Chistyakov, D. S. Kostyushev, V. P. Chulanov
Russian Journal of Infection and Immunity.2019; 9(3-4): 476. CrossRef
Hepatitis B virus surface gene pre‐S2 mutant as a high‐risk serum marker for hepatoma recurrence after curative hepatic resection
Chia‐Jui Yen, Yu‐Lin Ai, Hung‐Wen Tsai, Shih‐Huang Chan, Chia‐Sheng Yen, Kuang‐Hsiung Cheng, Yun‐Ping Lee, Chia‐Wei Kao, Yu‐Chun Wang, Yi‐Lin Chen, Cheng‐Han Lin, Tsunglin Liu, Huey‐Pin Tsai, Jen‐Ren Wang, Ih‐Jen Su, Wenya Huang
Hepatology.2018; 68(3): 815. CrossRef
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Yi Rang Kim, Mi Ran Byun, Jin Woo Choi
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Anastasiya Kostyusheva, Dmitry Kostyushev, Sergey Brezgin, Elena Volchkova, Vladimir Chulanov
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The Histologic Cut-off Point for Adjacent and Remote Non-neoplastic Liver Parenchyma of Hepatocellular Carcinoma in Chronic Hepatitis B Patients: Hae Yoen Jung, Soo Hee Kim, Jin Jing, Jae Moon Gwak, Chul Ju Han, Ja-June Jang, Kyoung-Bun Lee; Korean J Pathol. 2012;46(4):349-358. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.349

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Abstract PDF

Background

The molecular profile of peritumoral non-neoplastic liver parenchyma (PNLP) has recently been suggested as predictive factor of early and late recurrence of hepatocellular carcinoma (HCC). However, there is no definite cut-off point for tumor-free PNLP in terms of either histological or molecular changes. Therefore, our aim is to determine the numerical cut-off point for separating adjacent PNLP and remote PNLP in histopathologic perspective.

Methods

Peritumoral tissues from 20 resected HCC patients were sampled from 0 to 40 mm distance from the tumor border (divided into 5-mm columns). Histopathologic parameters such as necroinflammatory activity, fibrosis, bile ductular reaction, hepatic venulitis, peliosis, and steatosis were compared between each column.

Results

The morphologic changes just adjacent to the tumor were notably severe and faded with distance. The parenchyma within 10 mm of the tumor showed significantly severe inflammation, fibrosis, peliosis and hepatic venulitis compared with those from farther areas. The histopathologic changes of the parenchyma became stable beyond 20 mm.

Conclusions

Results of this study revealed that the parenchyma within 10 mm distance from the tumor, or adjacent PNLP, has histopathologic changes that are directly affected by the tumor, and the parenchyma beyond 20 mm as the remote PNLP without tumor effect.

Citations

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Peritumoral histopathologic findings in patients with chronic viral hepatitis‐associated hepatocellular carcinoma
Burcin Pehlivanoglu, Anil Aysal, Cihan Agalar, Tufan Egeli, Mucahit Ozbilgin, Tarkan Unek, Tugba Unek, Ilhan Oztop, Ozgul Sagol
APMIS.2022; 130(6): 346. CrossRef
Prognostic value of non-invasive fibrosis indices post-curative resection in hepatitis-B-associated hepatocellular carcinoma patients
Ting-Ting Zhang, Si-Si Ye, Jun Liang, Li Bai
Experimental Biology and Medicine.2020; 245(8): 703. CrossRef
Evaluation of Peritumoral Fibrosis in Metastatic Colorectal Adenocarcinoma to the Liver Using Digital Image Analysis
Kevin M Waters, Tricia R Cottrell, Sepideh Besharati, Qingfeng Zhu, Robert A Anders
American Journal of Clinical Pathology.2019; 151(2): 226. CrossRef
Fibrosis-4 Model Influences Results of Patients with Hepatocellular Carcinoma Undergoing Hepatectomy
Haiqing Wang, Aixiang Liu, Wentao Bo, Xielin Feng, Yong Hu, Lang Tian, Hui Zhang, Xiaoli Tang, Lixia Zhang
BioMed Research International.2018; 2018: 1. CrossRef
Forns index predicts recurrence and death in patients with hepatitis B‐related hepatocellular carcinoma after curative resection
Won‐Mook Choi, Jeong‐Hoon Lee, Hongkeun Ahn, Hyeki Cho, Young Youn Cho, Minjong Lee, Jeong‐ju Yoo, Yuri Cho, Dong Hyeon Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Nam‐Joon Yi, Kwang‐Woong Lee, Yoon Jun Kim, Jung‐Hwan Yoon, Kyung‐Suk Suh, Chung Yong Kim, Hy
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Renal Histologic Parameters Influencing Postoperative Renal Function in Renal Cell Carcinoma Patients
Myoung Ju Koh, Beom Jin Lim, Kyu Hun Choi, Yon Hee Kim, Hyeon Joo Jeong
Korean Journal of Pathology.2013; 47(6): 557. CrossRef

Clinicopathologic Features of Q Fever Patients with Acute Hepatitis: Miji Lee, Jae Jeong Jang, Yang Soo Kim, Sang-Oh Lee, Sang-Ho Choi, Sung-Han Kim, Eunsil Yu; Korean J Pathol. 2012;46(1):10-14. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.10

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Abstract PDF

Background

Q fever caused by Coxiella burnetii presents with diverse clinical and pathological features including subclinical or cholestatic hepatitis. However, the pathological features of liver biopsies from patients with Q fever have not been well described.

Methods

Clinical features and pathological findings of liver biopsies were reviewed in seven cases of Q fever that were confirmed by serological, microbiological, or molecular tests.

Results

All cases presented with fever. Liver enzymes were mildly elevated except one case with marked hyperbilirubinemia. Characteristic fibrin ring granulomas were present in three cases, epithelioid granulomas with eosinophilic infiltration in two cases, extensive extravasated fibrins without ring configuration mimicking necrotizing granuloma in one case, and acute cholangitis without granuloma in one case. All cases were treated with antibiotics for 20 days. Six cases were completely cured, but one suffered from multiorgan failure.

Conclusions

C. burnetii infection is uncommon, but should always be considered in patients with acute hepatitis and fever. Because variable-sized circumferential or radiating fibrin deposition was a consistent feature of the present cases, Q fever can be strongly suggested by pathological features and confirmed by serological and/or molecular tests.

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Q fever as a cause of fever of unknown origin in a patient on hemodialysis
Emilio Guirao-Arrabal, Ana Delgado-Ureña, Elena Borrego-García, Rosa Ríos-Pelegrina
Nefrología.2024; 44(6): 906. CrossRef
(Seltene) infektiöse Hepatitiden als wichtige Differenzialdiagnose der unklaren Hepatopathie
Michael Wührl, Marc Ringelhan, Ursula Ehmer, Jochen Schneider, Juliane Kager, Tobias Lahmer, Anna Schneider, Wilko Weichert, Carolin Mogler
Die Pathologie.2023; 44(1): 53. CrossRef
Sero-epidemiological study of zoonotic bacterial abortifacient agents in small ruminants
Muhammad Abid Zeeshan, Sarmad Ali, Ishtiaq Ahmed, Aziz ur Rehman, Muhammad Kamran Rafique, Amar Nasir, Aman Ullah Khan, Muhammad Kashif, Katja Mertens-Scholz, Muhammad Imran Arshad, Syed Ehtisham-ul-Haque, Heinrich Neubauer
Frontiers in Veterinary Science.2023;[Epub] CrossRef
The First Case of Coxiella Burnetti Infection Detected Through Bone Marrow Biopsy in Vietnam
Do Thi Vinh An, Bui Thi Viet Ha, Dao Xuan Co, Vu Minh Tam, Le Thi Diem Tuyet, Vu Van Truong
Clinical Pathology.2022;[Epub] CrossRef
Pathological study and molecular detection of zoonotic diseases in small ruminants at slaughter houses in Mymensingh, Bangladesh
Nazneen Sultana, Munmun Pervin, Sajeda Sultana, Mahmuda Islam, Moutuza Mostaree, Mohammad Abu Hadi Noor Ali Khan
Veterinary World.2022; : 2119. CrossRef
The First Report of Coxiella burnetii as a Potential Neglected Pathogen of Acute Hepatitis of Unknown Causes in Egypt
Mohamed A. El-Mokhtar, Ibrahim M. Sayed, Ayat M. Kamel, Ahmed Atef Mesalam, Elsayed A. Elgohary, Khaled Abo bakr Khalaf, Sara Adel, Azza Abo Elfadl, Walaa A. Khalifa, Haidi Karam-Allah Ramadan
Microorganisms.2022; 10(11): 2168. CrossRef
A case of coexistent acute severe alcoholic and Q fever hepatitis: The useful contribution of repeated liver biopsies
Zampaglione Lucia, Bornand Aurélie , Goossens Nicolas , Ramer Lucas , Magini Giulia , Ongaro Marie , Cerny Andreas , Rubbia-Brandt Laura , Jean-Louis Frossard, Spahr Laurent
Annals of Clinical Gastroenterology and Hepatology.2022; 6(1): 034. CrossRef
Q-fever associated granulomatous hepatitis
Nicolas Dauby, Maria Gomez Galdon, Isabel Montesinos, Marjan Van Esbroeck, Thomas Sersté
International Journal of Infectious Diseases.2020; 95: 113. CrossRef
Pathologic changes and immune responses against Coxiella burnetii in mice following infection via non-invasive intratracheal inoculation
Xueyuan Hu, Yonghui Yu, Junxia Feng, Mengjiao Fu, Lupeng Dai, Zhiyu Lu, Wenbo Luo, Jinglin Wang, Dongsheng Zhou, Xiaolu Xiong, Bohai Wen, Baohua Zhao, Jun Jiao, Daniel E. Voth
PLOS ONE.2019; 14(12): e0225671. CrossRef
Fibrin Ring Granulomas in Checkpoint Inhibitor-induced Hepatitis
Jamie Everett, Amitabh Srivastava, Joseph Misdraji
American Journal of Surgical Pathology.2017; 41(1): 134. CrossRef
Clinical and Genetic Features ofCoxiella burnetiiin a Patient with an Acute Febrile Illness in Korea
Seung Hun Lee, Jung Yeon Heo, Hae Kyung Lee, Yeong Seon Lee, Hye Won Jeong, Seon Do Hwang
Journal of Korean Medical Science.2017; 32(6): 1038. CrossRef
Q Fever Presented as a Large Retroperitoneal Pseudotumoral Mass
Behdokht Nowroozizadeh, Negar Haghighi Mehmandari, Nicolas Gallegos, Mari Perez-Rosendahl, Di Lu
Case Reports in Pathology.2017; 2017: 1. CrossRef
From Q Fever to Coxiella burnetii Infection: a Paradigm Change
Carole Eldin, Cléa Mélenotte, Oleg Mediannikov, Eric Ghigo, Matthieu Million, Sophie Edouard, Jean-Louis Mege, Max Maurin, Didier Raoult
Clinical Microbiology Reviews.2017; 30(1): 115. CrossRef
Prolonged Pyrexia and Hepatitis: Q fever
Caitlin Dugdale, Brian Chow, Evgeny Yakirevich, Erna Kojic, Bettina Knoll
The American Journal of Medicine.2014; 127(10): 928. CrossRef

Frequency of Intrahepatic FoxP3+ Regulatory T cells during the Natural Course of Chronic Hepatitis B: An Immunohistochemical Study Using Needle-Biopsied Liver Tissue.: Ji Yoon Bae, Hyung Kyung Kim, Hanna Kang, Ha Rin Cheong, Dong Eun Song, Sun Hee Sung, Heasoo Koo, Woon Sup Han, Jeong Kyong Lee, Tae Hun Kim, Kyu Won Chung, Min Sun Cho; Korean J Pathol. 2010;44(2):132-140.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.132

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Abstract PDF

BACKGROUND
Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized.
METHODS
Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry.
RESULTS
The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load.
CONCLUSIONS
FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.

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Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer
Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung
The Korean Journal of Pathology.2011; 45(1): 53. 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.

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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
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

The Clinicopathological Parameters for Making the Differential Diagnosis of Neonatal Cholestasis.: Heejin Lee, Jun Kang, Kyung Mo Kim, Joo Young Jang, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2009;43(1):43-47.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.43

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Abstract PDF

BACKGROUND
The diseases that cause neonatal cholestasis display several overlapping clinical feature. Making the differential diagnosis using liver biopsy specimens from infants with neonatal cholestasis is important for delivering the proper treatment.
METHODS
We assessed the clinical manifestations, laboratory data, and histopathologic features of the pretreatment liver biopsy specimens from patients suffering with biliary atresia (n=66), intrahepatic bile duct paucity (n=15), and neonatal hepatitis (n=21).
RESULTS
The gender distribution was nearly equal for the patients with biliary atresia and intrahepatic bile duct paucity, whereas males predominated for the cases of neonatal hepatitis. Only the gamma-glutamyl transferase level differed significantly amongst the groups. The diagnostic features for making the differential diagnosis of bile duct lesions included marked bile ductular proliferation, severe fibrosis, and bile duct loss. The difference of the average percentage of portal tracts with bile duct loss was statistically significant between the patients with intrahepatic bile duct paucity (73.9%) and those patients with neonatal hepatitis (39.1%) (p<0.001).
CONCLUSIONS
Bile ductular proliferation, bile duct loss, and advanced fibrosis are useful for the differential diagnosis of neonatal cholestasis. Moreover, stricter diagnostic criteria for bile duct loss (more than 2/3 of bile ducts) should be applied for the definitive diagnosis of intrahepatic bile duct paucity, because bile duct loss also frequently occurs in infants suffering with neonatal hepatitis.

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Hyunji Kim, Sujin Park, Sejin Ha, Jae Seung Kim, Dae Yeon Kim, Minyoung Oh
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Detection of HBV DNA in Needle Biopsied Paraffin Embedded Liver Tissues of Chronic Hepatitis B Patients by PCR: Comparison with Serological and Immunohistochemical Studies.: Hye Soo Lee, Kahng Yeul Oh, Joo Heon Kim, Yoon Jeong Kim, Sam Im Choi, Dong Geun Lee, Sang Ho Kim; Korean J Pathol. 1996;30(6):495-504.

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Abstract PDF: In this study, the prevalence of Hepatitis B virus(HBV) DNA in the needle biopsied paraffin embedded liver tissues of chronic hepatitis B patients by rapid nested PCR was examined. DNA was extracted by NaOH with boiling, and amplified by rapid air thermocycler with glass capillary tubes and nested PCR with two primer sets specific for the surface and the core genes of HBV. The PCR results were compared to that of serum HBeAg, serum HBV DNA by dot blot hybridization with a radioactive DNA probe, and tissue immunohistochemical (HBsAg/ HBcAg) studies. Among 44 patients with chronic hepatitis with serum HBsAg positivity, HBV DNA could be detected by PCR in 43 liver tissues (98%). This results were comparable to the positive rates of 94%(31/33) for serum HBV DNA, 80%(35/44) for serum HBeAg, and 59%(26/44) and 75%(33/44) for tissue HBsAg and HBcAg, respectively. The accordance rate between tissue PCR and serum DNA probe testing was 91%. The results indicate that HBV DNA detection by rapid nested PCR of paraffin embedded liver tissues by needle biopsy is a more sensitive method to detect the HBV DNA carrier than the serum HBeAg or tissue HBsAg/HBcAg status, and is well correlated with the result of serum HBV DNA probe testing. Therefore this method is a practical indicator for the diagnosis and replication status in retrospective analysis.

Primary Biliary Cirrhosis-Autoimmune Hepatitis Overlap Syndrome.: Jong Yup Bae, Young Nyun Park, Chanil Park; Korean J Pathol. 1997;31(1):87-90.

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Abstract PDF: Cases sharing features of both primary biliary cirrhosis and autoimmune hepatitis have been reported as a mixed type, overlap syndrome, immunocholangitis and autoimmune cholangiopathy. A primary biliary cirrhosis- autoimmune hepatitis overlap syndrome is unusual and characterized by overlapping features; cholestasis, high titer of alkaline phosphatase, bile duct damage and granulomas in the liver biopsy, high antinuclear antibody, increased IgG and IgM and intra-acinar hepatitis with piecemeal necrosis. Autoimmune mechanisms are thought to play a major role in the pathogenesis of the overlapping syndrome and the bases of immunosuppressive therapy. A 58-year-old female patient shows overlapping clinical and laboratory findings, chronic active hepatitis in initial liver biopsy which transits to primary biliary cirrhosis with cholangitis and granulomas. This is a case of hepatobiliary lesion showing overlapping features of both primary biliary cirrhosis and autoimmune hepatitis over 3-year period.

Relationship between Proliferative Activity and Expression of HBcAg and p53 Protein in Hepatocellular Carcinoma and Surrounding Nontumorous Liver.: So Ya Paik, Ho Guen Kim, Chan Il Park; Korean J Pathol. 1997;31(8):773-781.

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Abstract PDF: In an attempt to discover the factors contributing to the increased proliferative activity in hepatocytes and subsequent development of HCC, the proliferative activity of hepatocytes was compared with the size of regenerative nodules and HBcAg expression status in the surrounding nontumorous liver of 45 surgically resected hepatocellular carcinomas, including 34 HBV related ones. In the tumor, the difference in proliferative activity and the histological grade was analyzed in terms of p53 gene alteration. The proliferative activity was assessed by immunohistochemical methods using Ki-67 monoclonal antibody. HBcAg expression in the surrounding nontumorous liver correlated with both the inflammatory and proliferative activity of hepatocytes (p<0.05). p53 overexpression was associated with high proliferative activity and aggressive phenotype of tumor. No correlation was observed between the proliferative activity of hepatocytes and the size of regenerative nodules in cirrhosis (p>0.05). p53 overexpression was not evident in surrounding nontumorous liver including cirrhosis. In conclusion, the above results are in line with the view that hepatic carcinogenesis is a mutistep, progressive process. In the initial stage, chronic cellular injury incurred by immumologic reaction against HBcAg seems to play a pivotal role in increased cellular regeneration. However, once transformation of hepatocytes occur the major contributor to tumor growth seems to be alteration in p53 tumor suppresor gene.

S100 Protein Positive Dendritic Cells in Liver Diseases.: Ghil Suk Yoon, Inchul Lee, Eunsil Yu; Korean J Pathol. 1998;32(8):590-595.

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Abstract: We describe S100 protein positive dendritic cells (S100+DCs) in various liver diseases including chronic viral hepatitis B and C (20 cases), liver cirrhosis (3 cases), hepatocellular carcinoma (2 cases), hepatolithiasis (6 cases), primary biliary cirrhosis (PBC) (2 cases), liver allograft rejection (9 cases), bile duct paucity (1 case), and Wilson's disease (1 case). By immunohistochemical analysis, S100+DCs were absent in fetal and normal livers, while they were variably present in inflammatory liver diseases. In chronic hepatitis and active cirrhosis, S100+DCs were most frequently located in periportal area, at lymphoid follicles within the portal tract, and at foci of spotty necrosis within the lobule. Frequency and intensity of S100+DCs were not related to etiologies of liver diseases, but they were correlated with the activity of hepatitis. In PBC, S100+DCs were found between biliary epithelial cells of the septal bile ducts, as well as, the periductal area of the portal tracts. A posttransplantation liver with features of moderate acute rejection revealed many S100+DCs in polymorphous portal infiltrates. In hepatocellular carcinomas, many S100+DCs were scattered between tumor cells. In the case of the Wilson's disease, S100+DCs were not noted. Presence of S100+DCs in various inflammatory liver diseases indicates that they play a central role as antigen presenting cells in immune responses of inflammatory liver diseases.

Histological Grading and Staging of Chronic Hepatitis Standardized Guideline Proposed by the Korean Study Group for the Pathology of Digestive Diseases .: Young Nyun Park, Ho guen Kim, Chae Yoon Chon, Jae Bok Park, Jin Hee Sohn, Seung Ha Yang, Eun Sil Yu, Mi Seon Lee, Ja June Jang, Hee Kyung Chang, Jong Jae Jeong, Dae Young Kang, Yong Il Kim, Chan Il Park; Korean J Pathol. 1999;33(5):337-346.

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Abstract PDF: The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice. Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.

Case Report

Chronic Hepatitis in the Idiopathic Hypereosinophilic Syndrome: A case report .: Kyeong Hee Kim, Hae Joung Sul, Sung Chul Jun, Dae Young Kang; Korean J Pathol. 1999;33(8):624-626.

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Abstract PDF: Chronic hepatitis associated with the idiopathic hypereosinophilic syndrome has been very rarely reported worldwide. Recently, we experienced a case of chronic hepatitis with piecemeal necrosis as the clinical feature of the idiopathic hypereosinophilic syndrome. The patient was a 49-year-old woman who complained of a mild fever, nausea, vomiting, and pain in the right upper quadrant. The eosinophil count of peripheral blood increased up to 14,020/microliter (64% of WBC). Liver biopsy specimen showed severe porto-periportal inflammation with marked eosinophilic infiltration and ballooning degeneration of hepatocytes. Corticosteroid therapy significantly normalized the eosinophil count of peripheral blood.

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