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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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  • 385 Download
  • 1 Web of Science
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AbstractAbstract 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.

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  • Histological and Molecular Evaluation of Liver Biopsies: A Practical and Updated Review
    Joon Hyuk Choi
    International Journal of Molecular Sciences.2025; 26(16): 7729.     CrossRef
Case Study
Article image
Uncommon granulomatous manifestation in Epstein-Barr virus–positive follicular dendritic cell sarcoma: a case report
Henry Goh Di Shen, Yue Zhang, Wei Qiang Leow
J Pathol Transl Med. 2025;59(2):133-138.   Published online October 31, 2024
DOI: https://doi.org/10.4132/jptm.2024.09.27
  • 3,698 View
  • 348 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • Mesenchymal Tumors of the Liver: An Update Review
    Joon Hyuk Choi, Swan N. Thung
    Biomedicines.2025; 13(2): 479.     CrossRef
  • EBV-positive inflammatory follicular dendritic cell sarcoma occurring in different organs: a case report and literature review
    Wenhua Bai, Chunfang Hu, Zheng Zhu
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Spleen EBV-positive inflammatory follicular dendritic cell sarcoma: a case report and literature review
    Yi Xiao, Lanlan Li, Xiumei Zhan, Juner Xu, Yewu Chen, Qiuchan Zhao, Yinghao Fu, Xian Luo, Huadi Chen, Hao Xu
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma of the liver: clinical features, imaging findings and potential diagnostic clues
    Gui-Ling Huang, Man-Qian Huang, Yu-Ting Zhang, Hui-Ning Huang, Hong-Tao Liu, Xiao-Qing Pei
    Abdominal Radiology.2025;[Epub]     CrossRef
  • Epstein‑Barr virus+ inflammatory follicular dendritic cell sarcoma with clonal immunoglobulin heavy chain gene rearrangement: A case report and literature review
    Qian Ye, Juan Zhao, Jiao He, Weishan Zhang
    Oncology Letters.2025; 31(2): 1.     CrossRef
  • Primary hepatic follicular dendritic cell sarcoma: A case study and literature review
    Junjie Zhu, Ying Liang, Li Zhang, Bingqi Li, Danfeng Zheng, Hangyan Wang
    Journal of International Medical Research.2025;[Epub]     CrossRef
Original Articles
Article image
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
  • 12,143 View
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  • 12 Web of Science
  • 11 Crossref
AbstractAbstract PDF
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.

Citations

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  • Preclinical liver toxicity models: Advantages, limitations and recommendations
    Devaraj Ezhilarasan, Sivanesan Karthikeyan, Mustapha Najimi, Paramasivan Vijayalakshmi, Ganapathy Bhavani, Muthukrishnan Jansi Rani
    Toxicology.2025; 511: 154020.     CrossRef
  • Hepatic miR-93 promotes the pathogenesis of metabolic dysfunction-associated steatotic liver disease by suppressing SIRT1
    Yo Han Lee, Jinyoung Lee, Joonho Jeong, Kieun Park, Bukyung Baik, Yuseong Kwon, Kimyeong Kim, Keon Woo Khim, Haneul Ji, Ji Young Lee, Kwangho Kim, Ji Won Kim, Tam Dao, Misung Kim, Tae Young Lee, Yong Ryoul Yang, Haejin Yoon, Dongryeol Ryu, Seonghwan Hwang
    Metabolism.2025; 169: 156266.     CrossRef
  • Deep learning-based method for grading histopathological liver fibrosis in rodent models of metabolic dysfunction-associated steatohepatitis
    Soo Min Ko, Jae-ik Shin, Yiyu Hong, Hyunji Kim, Insuk Sohn, Ji-Young Lee, Hyo-Jeong Han, Da Som Jeong, Yerin Lee, Woo-Chan Son
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Liver biopsy in the modern era: from traditional techniques to artificial intelligence and multi-omics integration
    Nasar Alwahaibi, Maryam Alwahaibi
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Presurgery health influences outcomes following vertical sleeve gastrectomy in adolescents
    Debi Swertfeger, Ahlee Kim, Hannah Sexmith, Maria E. Moreno‐Fernandez, W. Sean Davidson, Michael Helmrath, Todd Jenkins, Tsuyoshi Okura, Esmond Geh, Stavra A. Xanthakos, Sara Szabo, Takahisa Nakamura, Senad Divanovic, Amy Sanghavi Shah
    Obesity.2024; 32(6): 1187.     CrossRef
  • Immunobiotic Bacteria Attenuate Hepatic Fibrosis through the Modulation of Gut Microbiota and the Activation of Aryl‐Hydrocarbon Receptors Pathway in Non‐Alcoholic Steatohepatitis Mice
    Paulraj Kanmani, Julio Villena, Soo‐kyoung Lim, Eun‐Ji Song, Young‐Do Nam, Hojun Kim
    Molecular Nutrition & Food Research.2024;[Epub]     CrossRef
  • Lipid nanoparticle-mediated hepatocyte delivery of siRNA and silibinin in metabolic dysfunction-associated steatotic liver disease
    Yifu Lyu, Xiuyi Yang, Lei Yang, Jinyu Dai, Huanyu Qin, Yunuo Zhou, Yunan Huang, Yanmei Wang, Di Wu, Qindai Shuai, Qilong Li, Xiaofei Xin, Lifang Yin
    Journal of Controlled Release.2024; 373: 385.     CrossRef
  • Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction‐associated steatohepatitis in mice by boosted modulation of metabolic, oxidative stress, and inflammatory pathways
    Wesam F. Farrash, Shakir Idris, Mohamed E. Elzubier, Elshiekh B. A. Khidir, Akhmed Aslam, Abdulrahman Mujalli, Riyad A. Almaimani, Ahmad A. Obaid, Mahmoud Z. El‐Readi, Mohammad A. Alobaidy, Afnan Salaka, Afnan M. Shakoori, Alaa M. Saleh, Faisal Minshawi,
    International Journal of Experimental Pathology.2024; 105(6): 219.     CrossRef
  • Bilirubin, a hepatoprotective agent that activates SIRT1, PGC-1α, and PPAR-α, while inhibiting NF-κB in rats with metabolic-associated fatty liver disease
    Motahareh Taghizadeh, Mohammad Hasan Maleki, Omid Vakili, Ramin Tavakoli, Parvin Zarei, Amirreza Dehghanian, Hossein Bordbar, Sayed Mohammad Shafiee
    Scientific Reports.2024;[Epub]     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.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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  • 7 Web of Science
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AbstractAbstract 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.

Citations

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  • Plasma thrombomodulin is a valuable biomarker to predict the severity of hemorrhagic fever with renal syndrome caused by the Hantaan virus
    Han-Dong Zhao, Yan Zhang, Xiao-Hong Wang, Hong-Bo Qian, Tong-Bo Yu, Peng Li, Kang-Xiao Ma, Hong-Li Liu
    Frontiers in Cellular and Infection Microbiology.2025;[Epub]     CrossRef
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    Hyeokjun Yun, Jong Wan Kim, Jae Kyung Kim
    Viruses.2025; 17(9): 1208.     CrossRef
  • 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
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    Keping Chen, Huidi Sun, Yu Geng, Chuankun Yang, Chun Shan, Yuxin Chen
    Frontiers in Microbiology.2023;[Epub]     CrossRef
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    Lihe Che, Zedong Wang, Na Du, Liang Li, Yinghua Zhao, Kaiyu Zhang, Quan Liu
    Frontiers in Microbiology.2022;[Epub]     CrossRef
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    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
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    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
  • 19,706 View
  • 103 Download
  • 11 Web of Science
  • 9 Crossref
AbstractAbstract 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.

Citations

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  • Triphasic CT Radiomics Model for Preoperative Prediction of Hepatocellular Carcinoma Pathological Grading
    Haibo Huang, Xianpan Pan, Yingdan Zhang, Jie Yang, Lei Chen, Qinping Zhao, Lifeng Huang, Wei Lu, Yaohong Deng, Yingying Huang, Ke Ding
    Journal of Hepatocellular Carcinoma.2025; Volume 12: 1725.     CrossRef
  • Upregulation of Keratin 19 Expression by Hepatitis B Virus X Protein Promotes Hepatocellular Carcinoma Invasion, Metastasis, and Postoperative Recurrence
    Jingyao Shen, Jie Zhang, Weimin Sun
    Hepatitis Monthly.2025;[Epub]     CrossRef
  • 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
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    Lei Wang, Jin-Lin Peng, Ji-Zhou Wu
    Medicine.2023; 102(13): e33319.     CrossRef
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    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
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    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
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    Yi Rang Kim, Mi Ran Byun, Jin Woo Choi
    Cancer Biomarkers.2018; 23(1): 135.     CrossRef
  • Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure
    Anastasiya Kostyusheva, Dmitry Kostyushev, Sergey Brezgin, Elena Volchkova, Vladimir Chulanov
    Genes.2018; 9(10): 483.     CrossRef
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
  • 8,926 View
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  • 8 Crossref
AbstractAbstract 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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  • Does very high alpha-fetoprotein affect very early hepatocellular carcinoma receiving hepatectomy?
    Hong-Shiue Chou, Chen-Fang Lee, Hao-Chien Hung, Yin Lai, Jin-Chiao Lee, Yu-Chao Wang, Chih-Hsien Cheng, Tsung-Han Wu, Ting-Jung Wu, Kun-Ming Chan, Wei-Chen Lee
    Langenbeck's Archives of Surgery.2025;[Epub]     CrossRef
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    Hannaneh Vossoughi, Pejman Mortazavi, Mahsa Ale-Ebrahim, Razieh Hosseini
    Toxicology Reports.2025; 15: 102115.     CrossRef
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    Burcin Pehlivanoglu, Anil Aysal, Cihan Agalar, Tufan Egeli, Mucahit Ozbilgin, Tarkan Unek, Tugba Unek, Ilhan Oztop, Ozgul Sagol
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    Ting-Ting Zhang, Si-Si Ye, Jun Liang, Li Bai
    Experimental Biology and Medicine.2020; 245(8): 703.     CrossRef
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    Kevin M Waters, Tricia R Cottrell, Sepideh Besharati, Qingfeng Zhu, Robert A Anders
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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
  • 11,707 View
  • 77 Download
  • 17 Crossref
AbstractAbstract 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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    Maxime Colson, Matthieu Million, Pierre-Edouard Fournier, Sophie Edouard
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    Mohammad Reza Mohammadi, Safoura Moradkasani, Mina Latifian, Saber Esmaeili
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    Emilio Guirao-Arrabal, Ana Delgado-Ureña, Elena Borrego-García, Rosa Ríos-Pelegrina
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    Emilio Guirao-Arrabal, Ana Delgado-Ureña, Elena Borrego-García, Rosa Ríos-Pelegrina
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    Microorganisms.2022; 10(11): 2168.     CrossRef
  • A case of coexistent acute severe alcoholic and Q fever hepatitis: The useful contribution of repeated liver biopsies
    Lucia Zampaglione, Aurélie Bornand, Nicolas Goossens, Lucas Ramer, Giulia Magini, Marie Ongaro, Andreas Cerny, Laura Rubbia-Brandt, Jean-Louis Frossard, Laurent Spahr
    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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AbstractAbstract 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.

Citations

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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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AbstractAbstract 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 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
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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AbstractAbstract 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
    Nuclear Medicine and Molecular Imaging.2019; 53(5): 356.     CrossRef
  • Morphometric assessment of liver fibrosis may enhance early diagnosis of biliary atresia
    Ahmed F. Abdalla, Abeer Fathy, Khaled R. Zalata, Ahmed Megahed, Ahmed Abo-Alyazeed, Mohammed Ezz El regal
    World Journal of Pediatrics.2013; 9(4): 330.     CrossRef
  • Differential hepatic expression of CD56 can discriminate biliary atresia from other neonatal cholestatic disorders
    Mostafa Mohamed Sira, Mohamed Abdel-Salam El-Guindi, Magdy Anwar Saber, Nermin Ahmad Ehsan, Marwa Sabry Rizk
    European Journal of Gastroenterology & Hepatology.2012; 24(10): 1227.     CrossRef
  • Biliary Atresia: A Multidisciplinary Approach to Diagnosis and Management
    Roger Klein Moreira, Rodrigo Cabral, Robert A. Cowles, Steven J. Lobritto
    Archives of Pathology & Laboratory Medicine.2012; 136(7): 746.     CrossRef
  • Tentative Proposal of Optimal Timing of Kasai Operation for Biliary Atresia Based on Fibroscan Results
    Hwa Young Lee, Young A Park, Seok Joo Han, Hong Koh
    Korean Journal of Pediatric Gastroenterology and Nutrition.2011; 14(1): 74.     CrossRef
Histologic Pattern of Alcoholic Liver Disease in Korea.
Chan Il Park, Ho Guen Kim, So Young Jin, Mi Kyung Lee, Yoo Bock Lee
Korean J Pathol. 1989;23(3):292-304.
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AbstractAbstract PDF
To elucidate the histologic pattern of alcoholic liver disease (ALD) in Korea, liver biopsies from 173 chronic alcoholics with clinical liver diseases were classified according to the pathologic parameters. One hundred and seventeen cases, the sum of 91 of 116 serum HBsAg negative and 26 of 57 HBsAg positive patients, had the histologic evidence of ALD. Fatty change(23.9%), alcoholic fibrosis (AF)(23.1%) and cirrhosis (23.1%), comprised the three major ALDs, and only 8.5% of cases fit the criteria of alcoholic hepatitis. Chronic sclerosing hyaline disease (CSHD), chronic active alcoholic hepatitis (CAAH) and AF, where non-cirrhotic fibrosis is the predominant change, comprised 44.5% of ALD. Both features of ALD and HBV liver disease (HBV-LD) were found in 17 cases that included 8 AF and 7 cirrhosis. These 17 patients tended to consume less alcohol than patients with other types of pure ALD except alcoholic heaptitis. Patients with the serum HBsAg positive ALD (37.4years) were about 8 years younger than those with the serum HBsAg negative ALD (45.1years). More or less fatty change and foamy degeneration were seen in 77.4% and 31.6% of ALD respectively. Mallory bodies, megamitochondria, iron deposition and perihepatocellular fibrosis were found in 20.5%, 29.9%, 42.7% and 77.8%, respectively. These findings indicate that non-cirrhotic chronic ALD such as CSHD, CAAH and AF are the important histologic patterns of ALD in Korea, and that chronic alcohol consumption and HBV may act synergistically in developing liver disease.
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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AbstractAbstract 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.
Expression pattern of Hepatitis B Viral Core Antigen (HBcAg) and Surface Antigen (HBsAg) in Liver of the Inactive HBsAg Carriers.
Hee Jeong Ahn, Kyoung Ho Kim, Young Nyun Park, Ho Guen Kim, Chan Il Park
Korean J Pathol. 1990;24(2):120-127.
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AbstractAbstract PDF
To understand better the complex natural course of HBV infection, the expression patterns of HBcAg and HBsAg in the liver of 51 inactive serum HBsAg carriers (24 CPH and 27 NPD) were studied by immunohistochemical methods. The inactive serum HBsAg carriers were devided into 3 groups by the following expression patterns of serum HBeAg/anti-HBe status and tissue HBcAg and HBsAg. Pattern A (18 cases) : HBeAg+, cHBcAg+ (94.4%), mHBsAg+ (61.1%), pATTERN B (14 cases) : anti-HBe+, nHBcAg+, cHBsAg+, Pattern C (19 cases) : anti-HBe+, HBcAg-, cHBsAg+ (89.5%). There were no significant differences between CPH and NPD, lthough the core free pattern was more common in the latter. The cHBcAg was expressed in 17 of 18 (94.4%) HBeAg seropositive cases but only one of 33 cases with serum anti-HBe, suggesting that the cHBcAg is intimately related to HBeAg. Since the inactive HBsAg carriers also expressed cHBcAg and/or mHBsAg, the necro-inflammatory activity of HBV infected liver is assumed to depend on the host immune response rather than their presence alone
Alcoholic Type Cirrhosis Following Side to Side Ileo-Transverse Colon Anastomosis.
Kwang Hwa Park, Kwang Hyup Han, Chan Il Park
Korean J Pathol. 1990;24(2):148-152.
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AbstractAbstract PDF
A case of micronodular cirrhosis of the alcoholic type developed following an intestianl bypass surgery in a 47 year-old nonalcoholic male patient is presented. The patient denied any drug use of a long duration and had no diabetes mellitus. Five years before, a side to side ileo-transverse colon anastomosis had been performed for perforated intestinal tuberculosis at 1 m proximal to the ileocecal valve, bypassing a short segment of ileum (about 1.5 m) and transverse colon. The ileum distal to the perforated site had been found completely stenosed. He was severely lean with evidences of nutritional deficiency such as low serum levels of the albumin and vitamin B12. The liver biopsy showed a fatty change, Mallory bodies and perihepatocellular collagenosis within the cirrhotic nodules. The present case suggests that, when there are blind loop formation and nutritional deficiency, hepatic changes identical to those following jejunoileal bypass could develop even by reduction of a shore segment of the small intestine.
Differential Expression of Promyelocytic Leukemia Protein in Autoimmune Liver Diseases.
Hyun Jung Kim, Jung Sun Kim, Yong Sang Lee, Young Hwa Chung, Han Joo Lee, Dong Jin Suh, Chong Jai Kim, Eunsil Yu
Korean J Pathol. 2004;38(6):357-363.
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AbstractAbstract PDF
BACKGROUND
Promyelocytic leukemia protein (PML) is a primary biliary cirrhosis (PBC)-specific autoantigen. Anti-PML antibody is analyzed using cultured cells with patient sera, however, PML expression has rarely been examined in liver tissues.
METHODS
In the present study, PML expression was examined immunohistochemically in paraffin embedded liver needle biopsy specimens obtained from 20 cases of PBC, 10 cases of autoimmune cholangitis, 36 cases of autoimmune hepatitis and from 5 cases of noninflammatory livers.
RESULTS
Variable PML immunopositivity was detected in the bile duct epithelial cells of 18 (90.0%) of 20 PBC cases and in all 10 cases (100.0%) of autoimmune cholangitis, whereas it was only present in 6 (16.7%) of 36 cases of autoimmune hepatitis (p<0.001). In contrast, hepatocyte PML immunopositivity was higher in autoimmune hepatitis (33/36 cases, 90.8%), than in PBC (10/20 cases, 50.0%) or autoimmune cholangitis (3/10 cases, 30.0%) (p<0.05).
CONCLUSION
Our data indicate that the differential expression of PML is closely related to autoimmune liver diseases type, and suggest that the overexpression of PML protein in bile duct cells is associated with the development of autoantibodies in patients with PBC or autoimmune cholangitis. Furthermore, PML immunoreactivity may be useful for the diagnosis of autoimmune cholangitis and overlap syndrome.
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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AbstractAbstract 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.
Case Reports
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.
  • 2,032 View
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AbstractAbstract 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.
Recurrent Viral Hepatitis Following Liver Transplantation: Report of 4 Cases.
Sunhee Chang, Kwangseon Min, Jaegul Jung, Ghil Suk Yoon, Seung Kyu Lee, Yung Sang Lee, Eunsil Yu
Korean J Pathol. 2002;36(2):122-127.
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AbstractAbstract PDF
The recurrence of viral hepatitis B or C after liver transplantation is almost universal but their clinical courses and outcomes are vary widely. We investigated four cases of rapidly progressive and fatal recurrent viral hepatitis following liver transplantation, which were rapidly progressive and fatal. Case 1 was a 58-year-old male, who developed recurrent viral hepatitisC. Case 2, 3, and 4 were a 59-year-old female, a 42-year-old male, and a 50-year-old male, respectively, who developed recurrent viral hepatitis B. In cases 1 and 2, the histopathological features of the first liver biopsies were prominent ballooning degeneration of the hepatocytes but later biopsies revealed significant lobular activity. Case 3 began with a marked fatty change and mild lobular and porto-periportal activity and progressed to severe lobular activity and septal fibrosis. In case 4, the first liver biopsy revealed minimal lobular activity but the second biopsy revealed severe lobular activity.
Neonatal Giant Cell Hepatitis: An autopsy case.
Sung Churl Lim, Moo Young Song, Un Jun Hyung, Je G Chi
Korean J Pathol. 1991;25(2):147-152.
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AbstractAbstract PDF
We report an autopsy case of neonatal giant cell hepatitis that was presumed to be related to bacterial sepsis, endotoxemia and to the subsequent parenteral alimentation and antibiotics treatment. The patient died of candidal endocarditis and multiple brain infarcts. This female baby was born by a normal full term spontaneous delivery. Six days after delivery she developed fever and lethargy as she suffered from Cheyne-Stokes respiration with severe grunting. Blood culture grew Enterobacter and Acinetobacter. After management of the sepsis her general condition improved. On the 23rd day of admission she was found to have deep jaundice and hepatosplenomegaly. The liver became larger progressively and the edge was palpable at the umbilical level. Grade II systolic murmur was heard along the left lower sternal border. She died on the 31st day of hospitalization. Postmortem examination showed severe jaundice, hepatosplenomegaly, a large vegetation on the mitral valve and multiple petechial hemorrhages of the viscera. Microscopically the liver showed features of massive giant cell transformation, mild fibrosis and inflammatory cells, suggestive of giant cell hepatitis. Numerous yeasts and candidal pseudohyphae were seen in the cardiac vegetation, focally extending into the myocardium. There was a focus of candidal vasculitis in the bowel wall. In addition there were multiple bilateral organizing infarcts in the cerebral hemisphere as well as diffuse white matter damage associated with septicemia.
Combined IgA Nephropathy and Membranous Glomerulonephritis : A Report of Six Cases.
Ji Han Jung, Yeong Jin Choi, Yong Soo Kim, Yoon Sik Chang, Byung Kee Bang, Sang In Shim, Chang Suk Kang
Korean J Pathol. 2005;39(4):278-283.
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AbstractAbstract PDF
IgA nephropathy (IgAN) and membranous glomerulonephritis (MGN) are common in adults. However, it is unlikely that these two distinct glomerulonephrites coexist in a renal biopsy. Here, we report clinical and pathological data of six patients with concomitant existence of IgAN and MGN in renal biopsy specimens from 1990 to 2004. Five patients were male and one was female, and their ages ranged from 29 to 71 years. Four patients had microscopic hematuria, five had nephrotic range proteinuria, three had hepatitis B virus infections, three had rheumatoid factors, one had antinuclear antibodies. Two cases were developed after kidney transplant. Immunofluorescence microscopy showed characteristic findings of mesangial IgA deposits and granular IgG deposits on the capillary walls. These were confirmed by electron microscopic findings of immune-type electron-dense deposits in the mesangium and subepithelial capillary basement membranes. The pathogenesis and prognosis of the patients are discussed in this report.
Methotrexate Induced Chronic Active Hepatitis: A report of two cases.
Jee Young Han, Young Nyun Park, Chan Il Park, Chae Yoon Chon
Korean J Pathol. 1994;28(2):168-172.
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AbstractAbstract PDF
Although methotrexate(MTX) has been known to have many side effects, especially toxicity on the hemopoietic cells and the liver, it has been used as a potent anticancer drug and for the treatment of psoriasis or rheumatoid arthritis. The severity of hepatotoxicity varies from mild fatty change to chronic active hepatitis(CAH) and cirrhosis. We experienced two cases of MTXinduced CAH in patients with psoriasis, which prompted us to report in view of the absence of biopsy proven MTX hepatotoxicity in the Korean literature. Microscopically, the liver showed a distorted lobular architecture with portal fibrous expansion, piecemeal necrosis and bridging necrosis/fibrosis. The hepatic lobules revealed fatty changes of hepatocyte, focal hepatocytolysis, delicate collagen deposits along the space of Disse and the characteristically marked polyploid nuclear change of hepatocytes.
Original Articles
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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AbstractAbstract 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.
Neonatal Hepatitis and Extrahepatic Biliary Atresia : A Comparison by Scoring the Histological Parameters.
Sun Hee Sung, Woo Hee Jung, Ho guen Kim, Ki Sup Jeong, Chanil Park
Korean J Pathol. 1991;25(5):446-456.
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AbstractAbstract
Neonatal hepatitis(NH) and congenital extrahepatic biliary atresia(BA) are two major causes of neonatal cholestasis. The method of therapeutic trials for each disease is essentially different. Nonetheless it is very difficult to differentiate these diseases histologically, since most of the hepatic changes are mutual in both of them. This study is to aimed to find out major differences between the two by scoring various histological parameters. A total of 63 consecutive liver biopsies taken from 54 patients with suggested NH and BA were examined by applying morphometric scoring system. The detailed clinical histories, laboratory data including serology for HBsAg and TORCH infection and radiologic operative findings were reviewed. Among 54 patients, 27 were diagnosed as NH and 20 as BA. In two cases, features of both diseases were coexistent. The pathological diagnosis was not compatible with the final diagnosis in 5 cases(10.7%). In all of these 5 cases, biopsy had been performed at the age of one to two months. The seropositivity for TORCH was 59.3%(16.27) in NH, but 25.0%(5/20) in BA. Serum AST, ALT and alpha-fetoprotein values were higher in NH, and total bilirubin in BA. Of various histological parameters, scores of portal fibrosis, bile duct and ductular proliferation and bile thrombi were much higher in BA, and at the age of less than 2 months, extramedullary hemopoiesis(EMH) was found much more frequently in NH. Giant cell transformation of hepatocytes(GCT) was more commonly observed in NH. The numbers of GCT and EMH were particulary plentiful when the patients' sera were positive for HBsAg or TORCH. These results indicate that portal fibrosis, biliary proliferation and bile thrombi are the three major histologic features of BA, and therefore erroneous histological diagnosis may ensue when scores of those features are low as in some early BA.
Histopathologic Appearance of Cytomegaloviral Liver Diseases in Neonates and Infants.
Sun Hee Sung, Chan Il Park, Ho Guen Kim, Woo Hee Jung, Ki Sep Chung
Korean J Pathol. 1992;26(2):137-145.
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AbstractAbstract PDF
To provide ideas for the recognition of neonatal and infantile liver diseases caused by cytomegalovirus(CMV) infection, histopathological examinations were made on hepatic tissues obtained by biopsy or autopsy from 23 patients. All patients were sero-positive for IgM anti CMV and had no other known or suggested etiologic factors for their liver disease. There were five different types of liver diseases: 8 cases of giant cell hepatitis(34.8%), 4 cases of biliary atresia(17.4%), 5 cases of biliary atresia with changes of neonatal hepatitis(21.7%), 4 cases of diffuse hepatic fibrosis(17.4%) and 2 cases of hepatic necrosis with CMV inclusion(8.7%). The diffuse hepatic fibrosis involved both the hepatic lobules and portal areas without evidences of regeneration. This type of liver disease appeared to be a chronic progressive illness that began during the first week of life, and in 3 of 4 cases, the liver biopsy was dong at 5 to 9 months after birth. The two patients showing CMV inclusion in their liver were premature of debilitated, and died within I month after birth. Diffuse hepatic necrosis as well as the cytomegalic change of bile duct epithelium was characteristic. The findings suggest that the pattern of CMV liver disease depends on the major site of hepatic injury, the status of status of patient's defense mechanism and the chronicity of illness.
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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AbstractAbstract
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.
Clinico-pathological Study on Hepatitis B virus-Associated Nephropathy.
Moon Hyang Park, Hae Sun Ahn
Korean J Pathol. 1992;26(3):215-228.
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To clarify the characteristics of HBV-associated renal lesions, renal biopsies obtained from 22 HBsAg seropositive patients(M:F=32:1) were studied. Other than two(age 4 and 12), all were adults(17-77 y.o.). Twelve of the patients had nephrotic syndrome(NS), 5 NS and hematuria(H), 10 proteinuria and H, one gross H, one microscopic H, and 4 normal urinalysis at the time of biopsy. Light microscopy showed minimal change lesion(MCL) in 9 cases, mesangial proliferative glomerulonephritis(MSPGN) in 6, MPGN type I in 7, MPGN type III in 6, and mebranous nephropathy(MGN) in 5 cases. There were variable immunofluorescent(IF) findings of 25 cases studied; IF staining were predominant with IgG in 10 cases, with IgA in 5 and with IgM in 2 cases. Complements tended to be more strong for C1 &/or C4 than C3. In electron microscopic(EM) studies of MCL group, rare mesangial deposits were noted(3/5). In MSPGN, aside from mesangial deposits, there were occasional subendothelia(2/4) or subepithelial(1/4) deposits. In MPGN type I, in addition to the usual EM features of MPGN, some subepithelial deposits were also observed in 5 cases. In MGN, 3 out of 4 showed subendothelial deposits. Among 7 cases stained for HBsAg all were negative with IF and 2 were positive with PAP method. It is concluded that clinico-pathological findings of HBV-associated nephropathy are variable and partly show lupus-like features, different from primary glomerulopathy.
A Clinicopathologic Study on Chronic Alcoholic Hepatitis.
Gi Yeong Huh, Sun Kyung Lee
Korean J Pathol. 1988;22(4):393-403.
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This study was undertaken to evaluate the significant diagnostic points of chronic alcoholic hepatitis (CALH) among clinicopathologic findings observed. The specimens used in this study were 20 cases of CALH and 28 cases of chronic active viral hepatitis (CAVH), which were diagnosed at our University Hospital during 9 years period from 1978 to 1987. In these cases, comparative analysis of age and sex distribution, major clinical manifestations, and laboratory and histopathologic findings was performed. The results obained were summarized as follows: Among 20 cases of CALH, the sex distribution was 15 in male and 15 in female with a ratio of 3:1. The range of age distribution was wide from third to seventh decade. There was no recognizable special point about the age and sex distribution of CALH, compared with cases of CAVH. Major clinical manifestations of CALH were hepatomegaly (85%), jaundice (75%) and abdominal pain (50%). Also there was no recognizable special point about the major clinical manifestations of CALH, compared with cases of CAVH. Abnormal values of major laboratory items in CALH were observed in activities of serum r-GTP (100%), SGOT (95%), SGPT (75%) and serum alkaline phosphatase (60%), and total serum bilirubin (60%). Compared with CAVH in major laboratory findings, the significant diagnostic items of CALH were the activities of serum r-GTP and alkaline phosphatase. The characteristic histopathologic findings of CALH, which were compared with CAVH and observed in liver parenchyma, were fatty change (100%), cytoplasmic ballooning and coagulation (100%), delicate fibrosis (85%), bile stagnation (35%), and Mallory bodies (20%), and that observed blurring of limiting plate (60%) in portal and periportal areas.
Occurrence of Hepatitis B-Virus Antigens in a Consecutive Material of 112 Liver Biopsies.
S P Kim, C H Kim, S S Lee, C H Chung
Korean J Pathol. 1988;22(4):404-414.
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The frequency and occurrence of HBsAg and HBcAg in 112 consecutive, HBsAg sero-positive, liver biopsies were determined using immunoperxidase staining, HBsAg and HBcAg were demonstrated in 35 (31.3%) and 71 (63.4%) biopsies, respectively. HBsAg in liver was found in the cytoplasm as diffuse granules, mostly in the form of cytoplasmic inclusions. There was also perinuclear and membranous patterns. HBcAg in liver was found mostly in the cytoplasm and occasionally confined to the nucleus. The highest correspondence between HBsAg positivity in serum and liver was found in cases with normal histology morphology (80%). The frequency of HBs and HBcAg in liver in chronic liver disease was 23.1~50% and 36.4~69.2%. According to the variable expression pattern of HBs & c Ags in liver cells, 47 cases (42%) showed only HBcAg in liver. Twenty-nine cases (25.6%) failed to demonstrate any HBV Ags in liver and 24 cases showed boty antigens in liver. No correlation was found between liver disease groups and HBV Ag expression patterns. However, 11 cases (9.8%) showed only HBsAg in liver; predominant HBsAg pattern was observed in 80% of "normal histology group". 73.2% of HBsAg positive patients had anti-HBc in serum and 57.7% of them had HBeAg. 70.3% of anti-HBc positive and 70.7% of HBeAg sero-positive patients had HBcAg in liver cells. These findings strongly suggest that the presence of HBcAg. Serum HBeAg and anti-HBc can be used as a reliable indicator of active viral replication. The overall results further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis, including different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis.
Biologic Significance of Hepatocyte Hepatitis B Core Antigen Expression in Chronic Hepatitis B Virus Infection II.
Hye Kyung Lee, Kwang Min Lee, Dong Kyu Chung
Korean J Pathol. 1992;26(4):355-359.
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Routine use of commercially available antisera against hepatitis B core antigen(HBcAg) has permitted a reevaluation of the histochemical distribution of the antigen in liver tissue. HBcAg, classically described almost exclusively in the nucleus, was found with a very high frequency in the cytoplasm of liver cells as well. To elucidate the biologic significance of HBcAg expression and its relation to the natural course of hepatitis B virus(HBV) infection, the patterns of activity in 33 needle liver biopsies of HBsAg carriers were analysed. A good correlation of liver HBcAg with disease activity was demonstrated. HBcAg was present in the hepatocyte nuclei(nHBcAg) or cytoplasm(cHBcAg), or in both(mixed). Pure nHBcAg was seen mainly in non-aggressive reactive liver tissue and cHBcAg was predominantly associated with chronic active hepatitis(95%). The results suggest that expression of HBcAg correlates with the liver pathology and the possibility of HBcAg to be an immunological target for T cell mediated hepatocyte damage.
Liver in Systemic Lupus Erythematous: Clinicopathological analysis of 8 cases.
Young Nyun Park, Chan Il Park, Yoon Sok Chung, Si Young Song, Chein Soo Hong
Korean J Pathol. 1992;26(5):445-450.
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Hepatic changes in eight cases of systemic lupus erythematosus(SLE), were studied to evaluate the nature of hepatic injury of SLE and its relation to lupoid hepatitis. Common histologic changes of the liver in SLE included intralobular necro-inflammatory activities, fatty change, canalicular bile stasis and mild perivenular and Disse space fibrosis. The fatty change and intralobular fibrosis were thought not to be due to SLE itself but associated with steroid administration or chronic alcoholic consumption. The necro-inflammatory changes were usually mild and features of chronic active hepatitis with periportal destruction occured in one case. Symptoms related to the involvement of many other organs than the liver appeared much frequently in patients with SLE than lupoid hepatitis, suggesting that the SLE involving liver and the lupoid hepatitis are different diseases.
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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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.

J Pathol Transl Med : Journal of Pathology and Translational Medicine
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