Clinical and Molecular Hepatology

"Bile duct"

Original Article

Co-repression of Yap1 and Sox9 Abrogates Established Cholangiocarcinoma by Eliminating Transcriptional Compensation: Minwook Kim, Shikai Hu, Yoojeong Park, Joseph Kwon, Laura Molina, Li-Ju Wang, Jia-Jun Liu, Silvia Liu, Aatur Singhi, Yu-Chiao Chiu, Sungjin Ko; Received November 9, 2025 Accepted March 23, 2026 Published online April 3, 2026; DOI: https://doi.org/10.3350/cmh.2025.1170 [Accepted]

Abstract
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Background/Aims
Intrahepatic cholangiocarcinoma (iCCA) represents an unmet clinical need due to its increasing incidence, aggressive biology, and limited treatment options. The extremely low-response rates to current systemic regimens and the emergence of adaptive resistance to targeted therapies underscore the urgent need for alternative therapeutic strategies. Given that the lineage-defining transcription factors SOX9 and YAP1 are central regulators of cholangiocyte and iCCA identity, we investigated their functional roles as potential therapeutic vulnerabilities across multiple preclinical models.
Methods
Patient tissue-microarray (TMA) analysis, Sleeping-Beauty hydrodynamic tail vein injection–based iCCA models, and Cre-mediated inducible gene deletion systems were used to investigate the roles of Sox9 and Yap1. Deep-learning–based prediction, RNA-seq, ChIP-seq and immunohistochemistry analyses were performed to delineate transcriptional networks and downstream effectors associated with SOX9/YAP1 signaling.
Results
Dual deletion of Sox9 and Yap1 effectively eradicated advanced iCCA while preserving intrahepatic bile ducts, regardless of oncogenic drivers. Mechanistically, SOX9 and YAP1 transcriptionally compensated for each other when one was absent, and ILF2 and MGAT5 were identified as key downstream effectors mediating this compensatory mechanism. Loss of Ilf2 and Mgat5 suppressed iCCA, whereas overexpression of Ilf2 following Sox9/Yap1 co-deletion restored tumor development, indicating that ILF2 can functionally substitute for YAP1 and SOX9 in sustaining iCCA.
Conclusions
Co-targeting SOX9 and YAP1 offers a promising and safe broad-spectrum preventive/therapeutic approach for iCCA, potentially overcoming resistance to YAP1 inhibition. The adaptive resistance mechanism identified may extend to other malignancies, providing insights for addressing the advanced resistant to YAP1-TEAD-directed therapies.

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Reply to Correspondence

Cholestatic liver disease

Correspondence on Letter regarding “Both liver parenchymal and non-parenchymal cells express JCAD proteins under various circumstances”: Byoung Kuk Jang; Clin Mol Hepatol 2024;30(2):297-298.
Published online April 1, 2024; DOI: https://doi.org/10.3350/cmh.2024.0210

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Original Article

Hepatic neoplasm

Clinical features and outcomes of patients with hepatocellular carcinoma complicated with bile duct invasion: Jihyun An, Kwang Sun Lee, Kang Mo Kim, Do Hyun Park, Sang Soo Lee, Danbi Lee, Ju Hyun Shim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee; Clin Mol Hepatol 2017;23(2):160-169.
Published online May 16, 2017; DOI: https://doi.org/10.3350/cmh.2016.0088

Abstract
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Background/Aims
Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion.
Methods
A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included.
Results
The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively).
Conclusions
The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function.

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Liver Pathology

Hepatic neoplasm

Histopathology of a benign bile duct lesion in the liver: Morphologic mimicker or precursor of intrahepatic cholangiocarcinoma: Kyoung-Bun Lee; Clin Mol Hepatol 2016;22(3):400-405.
Published online September 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0105

Abstract
PDF

A bile duct lesion originating from intrahepatic bile ducts is generally regarded as an incidental pathologic finding in liver specimens. However, a recent study on the molecular classification of intrahepatic cholangiocarcinoma has focused on the heterogeneity of this carcinoma and has suggested that the cells of different origins present in the biliary tree may have a major role in the mechanism of oncogenesis. In this review, benign intrahepatic bile duct lesions—regarded in the past as reactive changes or remnant developmental anomalies and now noted to have potential for developing precursor lesions of intrahepatic cholangiocarcinoma—are discussed by focusing on the histopathologic features and its implications in clinical practice.

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Cancers.2026; 18(2): 328. CrossRef
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Keun Soo Ahn, Daniel O'Brien, Yoo Na Kang, Taofic Mounajjed, Hye Won Lee, Yong Hoon Kim, Tae-Seok Kim, Min Jae Kim, Jin-Yi Han, Mitesh J. Borad, Lewis R. Roberts
HPB.2026;[Epub] CrossRef
A deceptively benign biliary lesion revealing an ALK‐rearranged intrahepatic cholangiocarcinoma
Anne‐Cécile Brunac, Marie Danjoux, Hadrien Reboul, Ronan Guillemin, Fabrice Muscari, Janick Selves
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Original Article

Vascular disorders of liver

Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation: Ji Hye Jun, Jong Ho Choi, Si Hyun Bae, Seh Hoon Oh, Gi Jin Kim; Clin Mol Hepatol 2016;22(3):372-381.
Published online September 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0032

Abstract
PDF

Background/Aims
Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL).
Methods
The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP.
Results
The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP.
Conclusions
CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

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Liver Imaging

Hepatic neoplasm

Intraductal malignant tumors in the liver mimicking cholangiocarcinoma: Imaging features for differential diagnosis: Ah Yeong Kim, Woo Kyoung Jeong; Clin Mol Hepatol 2016;22(1):192-197.
Published online March 28, 2016; DOI: https://doi.org/10.3350/cmh.2016.22.1.192

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Maria Conticchio, Nicola Maggialetti, Marco Rescigno, Maria Chiara Brunese, Roberto Vaschetti, Riccardo Inchingolo, Roberto Calbi, Valentina Ferraro, Michele Tedeschi, Maria Rita Fantozzi, Pasquale Avella, Angela Calabrese, Riccardo Memeo, Arnaldo Scardap
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Intraductal Papillary Neoplasm of the Bile Duct: Clinical, Imaging, and Pathologic Features
Hyo Jung Park, So Yeon Kim, Hyoung Jung Kim, Seung Soo Lee, Gil Sun Hong, Jae Ho Byun, Seung-Mo Hong, Moon-Gyu Lee
American Journal of Roentgenology.2018; 211(1): 67. CrossRef

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Case Reports

Liver fibrosis, cirrhosis, and portal hypertension

Portal biliopathy treated with endoscopic biliary stenting: Sung Jin Jeon, Jae Ki Min, So Young Kwon, Jun Hyun Kim, Sun Young Moon, Kang Hoon Lee, Jeong Han Kim, Won Hyeok Choe, Young Koog Cheon, Tae Hyung Kim, Hee Sun Park; Clin Mol Hepatol 2016;22(1):172-176.
Published online March 28, 2016; DOI: https://doi.org/10.3350/cmh.2016.22.1.172

Abstract
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Portal biliopathy is defined as abnormalities in the extra- and intrahepatic ducts and gallbladder of patients with portal hypertension. This condition is associated with extrahepatic venous obstruction and dilatation of the venous plexus of the common bile duct, resulting in mural irregularities and compression of the biliary tree. Most patients with portal biliopathy remain asymptomatic, but approximately 10% of them advance to symptomatic abdominal pain, jaundice, and fever. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are currently used as diagnostic tools because they are noninvasive and can be used to assess the regularity, length, and degree of bile duct narrowing. Management of portal biliopathy is aimed at biliary decompression and reducing the portal pressure. Portal biliopathy has rarely been reported in Korea. We present a symptomatic case of portal biliopathy that was complicated by cholangitis and successfully treated with biliary endoscopic procedures.

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Benign liver tumors and cystic disease of liver

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein: Jem Ma Ahn, Yong-Han Paik, Jun Hee Lee, Ju Yeon Cho, Won Sohn, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Byung Chul Yoo; Clin Mol Hepatol 2015;21(4):393-397.
Published online December 24, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.4.393

Abstract
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A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.

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Bile duct adenoma: imaging features and radiologic–pathologic correlation
Ryoji Tatsumi, Shin Ichihara, Hirokazu Suii, Masakatsu Yamaguchi, Tomohiro Arakawa, Tomoaki Nakajima, Yasuaki Kuwata, Itaru Ozeki, Shuhei Hige, Joji Toyota, Yoshiyasu Karino
Japanese Journal of Radiology.2020; 38(6): 561. CrossRef

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Liver Imaging

Benign liver tumors and cystic disease of liver

Benign nodules mimicking hepatocellular carcinoma on gadoxetic acid-enhanced liver MRI: Kyoung Doo Song, Woo Kyoung Jeong; Clin Mol Hepatol 2015;21(2):187-191.
Published online June 26, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.2.187

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Wei Jiang, Dongbo Wu, Qin Li, Chang-Hai Liu, Qingmin Zeng, Enqiang Chen, Changli Lu, Hong Tang
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Suleyman Bakdik, Necdet Poyraz, Teyfik Kucukkartallar, Pembe Oltulu
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Ryoji Tatsumi, Shin Ichihara, Hirokazu Suii, Masakatsu Yamaguchi, Tomohiro Arakawa, Tomoaki Nakajima, Yasuaki Kuwata, Itaru Ozeki, Shuhei Hige, Joji Toyota, Yoshiyasu Karino
Japanese Journal of Radiology.2020; 38(6): 561. CrossRef
A case of reactive lymphoid hyperplasia of the liver in a patient with autoimmune hepatitis
Hiroki Kanno, Hisamune Sakai, Toru Hisaka, Satoki Kojima, Ryuta Midorikawa, Shogo Fukutomi, Yoriko Nomura, Yuichi Goto, Toshihiro Sato, Munehiro Yoshitomi, Ryuichi Kawahara, Koji Okuda
Surgical Case Reports.2020;[Epub] CrossRef
Reactive lymphoid hyperplasia of the liver
Wenyan Zhang, Shusen Zheng
Medicine.2019; 98(30): e16491. CrossRef
Hepatic pseudolymphoma: imaging features on dynamic contrast-enhanced MRI and diffusion-weighted imaging
Yang Zhou, XiaoLin Wang, Chen Xu, GuoFeng Zhou, MengSu Zeng, PengJu Xu
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Magnetic resonance findings of hepatic epithelioid hemangioendothelioma: emphasis on hepatobiliary phase using Gd-EOB-DTPA
Jeong Hyun Lee, Woo Kyoung Jeong, Young Kon Kim, Won Jae Lee, Sang Yun Ha, Kyoung Won Kim, Jihun Kim
Abdominal Radiology.2017; 42(9): 2261. CrossRef
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Yong Kyong Kwon
World Journal of Hepatology.2015; 7(26): 2696. CrossRef

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Case Report

Benign liver tumors and cystic disease of liver

Caroli's disease misdiagnosed as intraductal papillary neoplasm of the bile duct: Dae Hoe Gu, Min Seon Park, Chang Ho Jung, Yang Jae Yoo, Jae Young Cho, Yun Ho Lee, Yeon Seok Seo, Hyung Joon Yim, Soon Ho Um, Ho Sang Ryu; Clin Mol Hepatol 2015;21(2):175-179.
Published online June 26, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.2.175

Abstract
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Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy.

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Soukayna Bourabaa, Talha Laalou, Abderrahman Mansouri, Mohamed Hamid, Abdellatif Settaf
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Caroli syndrome in children: a brief review and clinical observation
R. A. Gudkov, A. V. Dmitriev, O. A. Slobodyanyuk
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Hepatic multiple hyperintense cystic lesions: a rare caroli disease.
Mohammed H. Alsharif, Nagi.M Bakhit, Abdulaziz Alarifi, Elbagir M. Nassir, Abair A. Mahdi, Juman M. Almasaad, Abubaker.Y. Elamin, Khalid M. Taha
THE NEW ARMENIAN MEDICAL JOURNAL.2023; (1, 17 (202): 41. CrossRef
Hepatic multiple hyperintense cystic lesions: a rare caroli disease
Mohammed H. Alsharif, Nagi M. Bakhit, Abdulaziz Alarifi, Elbagir M. Nassir, Abair A. Mahdi, Juman M. Almasaad, Abubaker Y. Elamin, Khalid M. Taha
THE NEW ARMENIAN MEDICAL JOURNAL.2023; (1, 17 (202): 41. CrossRef
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Jing Sun, Sheng Wang, Biquan Chen
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Roberto Cannella, Dario Giambelluca, Mariangela Diamarco, Giovanni Caruana, Giuseppe Cutaia, Massimo Midiri, Giuseppe Salvaggio
Current Problems in Diagnostic Radiology.2020; 49(4): 285. CrossRef
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Song Wang, Mei Xiao, Liqun Hua, Yong Jia, Si Chen, Kaiguang Zhang
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A. Deimel, J. Sturm, T. Vielfort, T. Zöpf
Der Internist.2018; 59(3): 276. CrossRef
Intraductal Papillary Neoplasm of the Bile Duct: Clinical, Imaging, and Pathologic Features
Hyo Jung Park, So Yeon Kim, Hyoung Jung Kim, Seung Soo Lee, Gil Sun Hong, Jae Ho Byun, Seung-Mo Hong, Moon-Gyu Lee
American Journal of Roentgenology.2018; 211(1): 67. CrossRef
The role of next generation sequencing in the differential diagnosis of caroli’s syndrome
B Smolović, D Muhović, A Hodžić, G Bergant, B Peterlin
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Diffuse-Type Caroli Disease with Characteristic Central Dot Sign Complicated by Multiple Intrahepatic and Common Bile Duct Stones
Moon Joo Hwang, Tae Nyeun Kim
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Should Caroli’s disease be in the Todani classification?
Özüm Tunçyürek, David J. Lomas
Abdominal Radiology.2016; 41(9): 1873. CrossRef

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Liver Pathology

Biliary intraepithelial neoplasia: a case with benign biliary stricture: Wonkyung Jung, Baek-hui Kim; Korean J Hepatol 2011;17(4):328-330.
Published online December 26, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.4.328

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Original Articles

Serum hyaluronic acid Level: Correlation with quantitative measurement of hepatic fibrosis in a cirrhotic rat model: Moon Young Kim, M.D., Soon Koo Baik, M.D., Yoon Ok Jang, M.D., Ki Tae Suk, M.D., Jae Woo Kim, M.D., Hyun Soo Kim, M.D., Mi Yun Cho, M.D.1, Sun Joo Choi, M.D.2, Soon Ho Um, M.D.3, Kwang-Hyub Han, M.D.4; Korean J Hepatol 2008;14(2):159-167.
Published online June 20, 2008; DOI: https://doi.org/10.3350/kjhep.2008.14.2.159

Abstract
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Backgrounds/Aims
The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model. Methods: Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-β (TGF-β) were measured by reverse transcriptase-polymerase chain reaction. Results: In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean±SD) were 0, 1.3±0.5, 2.6±0.5, and 3.4±0.5, respectively (P<0.05), serum HA levels were 12.5±3.2, 30.0±4.3, 228.6±157.7, and 391.3±207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4±2.8, 17.6±3.8, 17.9±2.4, and 33.4±3.4 μg/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-β1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-β1, and histomorphological grade of hepatic fibrosis (P<0.001).
Conclusions
These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis. (Korean J Hepatol 2008;14:159-167)

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Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats
Xiang-lan Wei, Ru-tang Fang, Yong-hua Yang, Xue-yuan Bi, Guo-xia Ren, A-li Luo, Ming Zhao, Wei-jin Zang
BMC Complementary and Alternative Medicine.2015;[Epub] CrossRef
Evaluation of Automated Assays for Measuring Serum Hyaluronic Acid: For the Diagnosis of Rheumatoid Arthritis
Mi-Soon Han, Yongjung Park, Hyon-Suk Kim
Laboratory Medicine Online.2014; 4(2): 98. CrossRef
Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension
Moon Young Kim, Mee Yon Cho, Soon Koo Baik, Hong Jun Park, Hyo Keun Jeon, Chong Kun Im, Chan Sik Won, Jae Woo Kim, Hyun Soo Kim, Sang Ok Kwon, Min Seob Eom, Seung Hwan Cha, Young Ju Kim, Sei Jin Chang, Samuel S. Lee
Journal of Hepatology.2011; 55(5): 1004. CrossRef
Diagnostic value of multiple biomarker panel for prediction of significant fibrosis in chronic hepatitis C
Seung Ha Park, Chang Hoon Kim, Dong Joon Kim, Ki Tae Suk, Jong Ha Park, Jae Youn Cheong, Sung Won Cho, Seong Gyu Hwang, Youn Jae Lee, Mong Cho, Jin Mo Yang, Ha Young Park, Young Bae Kim
Clinical Biochemistry.2011; 44(17-18): 1396. CrossRef
The value of serum retinol-binding protein 4 levels for determining disease severity in patients with chronic liver disease
Jung Hyun Kwon, Seong Tae Park, Gi Dae Kim, Chan Ran You, Jin Dong Kim, Hyun Young Woo, Jeong Won Jang, Chang Wook Kim, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
The Korean Journal of Hepatology.2009; 15(1): 59. CrossRef
Effects of silymarin and pentoxifylline on matrix metalloproteinase-1 and -2 expression and apoptosis in experimental hepatic fibrosis
Eray Kara, Teoman Coşkun, Yavuz Kaya, Okan Yumuş, Seda Vatansever, Ahmet Var
Current Therapeutic Research.2008; 69(6): 488. CrossRef

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Centrilobular Distribution of Ethylnitrosourea - Induced Hepatocellular Foci in the Mouse: Byoung Hun Kim , Soong Hwan Lee , Seong Kyu Yang , Jong Cheol Kim , Yeong Jung Cho , Yong Hyeon Jo , Byeong Moo Yoo , Chul Hun Jung , Dong Hoo Lee; Korean J Hepatol 1997;3(3):227-240.

Abstract
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Background/Aims
Hepatocytes on the hepatic lobule mipate from portal zone to centrilobular mea as the DNA synthesis within it. And also, the xenobiotic reactions reveal characteristic differences associated with zone specific metabolism in the liver acinus. In this study, the zonal distribution of ethylnitrosourea (ENU)-induced hepatic precancerous lesion was stereologically investigated. Methods: Nine B6C3F1 mices were given I.p. injection of ENU (60 ug/pn body weight) when the pups were 15 days old prior to sacrifices at 8 weeks of life. All the 150 consecutive sections, 3 p m in thickness, were stained with hematoxylin and eosin and identified the basophilic precancerous lesions with 80-165 p m diameter in equatorial plane by the Zeiss microprojector. And then the distances from the center of selected foci to terminal hepatic vein or portal vein branches were estimated under the microscopic fields. As a control group, the same estimations were performed from the random points by the appointments of random digit table. Results: Mean distance between ENU-induced 52 hepatocellular foci and the nearest terminal hepytic vein was 181.15+112.39 p m (Mean+ SD), but that of randomly selected 104 points was 291.73+157.98pm (Mean+5D) (Students t-test, p<0.0005). Substantially, 52.7% of ENU-induced 52 hepatocellular foci were within 300 p m from the terminal hepatic vein, but randomly selected 104 points were only 50.9% (Shapiro Wilk W test, w=0.819857, p=0.048038). Mean distance from ENU-induced 52 foci to portal vein was 398.85+149.98pm (Mean+SD), but that from the randomly selected 104 points was 315.87+145.79 pm (Mean+SD)(Students t-test, p<0.0005). Conclusion: Stereologically, ENU-induced mice liver cell foci distribute non-randomly to Zone III, centrilobular zone of mouse hepatic acini where promote invasion toward terminal hepatic veins. (Korean J Hepatol 1997;6:227 240)

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Induction of Rat Liver γ - Glutamyl Transpeptidase by Bile Acid Load: Sung Kook Kim , You Hee Kim; Korean J Hepatol 1997;3(3):210-226.

Abstract
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Background/Aims
In order to elucidate the possible mechanism of increase of y -glutamyl transpeptidase (y-GTP) activity in cholestatic liver and serum was studied. Method: Rats were divided into eight groups: Normal, sham operated control, bile duct obstruction (BDO) alone (BDO group), BDO plus taurocholic acid (TCA) injection (BDO plus TCA group), BDO plus tauroursodeoxycholic acid (TUDCA) injection (BDO plus TUDCA group), choledoco-caval shunt (CCS) operation (CCS groups), CCS plus TCA injection (CCS plus TCA group), and CCS plus TUDCA injection (CCS plus TUDCA group). Y -GTP activity was determined in the serum and liver cytosolic, mitochondrial and microsomal preparations isolated from above experimental rats. The values of Km and Vmax in this hepatic enzyme was measured. Result: the activities of liver cytosolic and microsomal y -GTP showed a significant increase in the CCS group. The activities of liver cytosolic, mitochondrial and microsomal y -GTP showed a significant increase in the BDO group. And the activity of serum y -GTP showed a marked increase in teth CCS and BDO poups. However, y-GTP activities in the serum and in liver microsomal prepatation rose more rapidly in the BDO group tban CCS. Y -GTP activity in liver cytosolic and microsomal preparatians, and its Vmax value incmmxl significantly in both CCS plus TCA group, and BDO plus TCA group than each control group, such as CCS and BDO group. On the other hand, the values of Km of the hepatic subcellular y -GTP did not change in the all experimental groups. Sennn y -GTP activity increased significantly in both CCS plus 7CA group, and BDO plus TCA group than each control group. However, these serum and hepatic enzyme activities did not change in both CCS plus TUDCA group and BDO plus TUDCA group. Conclusions: The above results suggest that 7CA stimulates biosynthesis of the y-GTP in the liver. And the elevations of the serum enzymes activity thought to be caused by increase of hepatocyte membrane permeability by a physical property (detergency) of TCA, which cause the enzyme to leak into the blood in large quantities. (Korean J Hepatol 1997;6:210 226)

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Ischemic Bile Duct Injury as A Serious Complication Following Transarterial Chemoembolization: Sang Soo Lee, M.D., Young-Hwa Chung, M.D., Hae Kyung Kim, M.D. Byung-Cheol Song, M.D.,Kung No Lee, M.D., Soo Hyun Yang, M.D. Jae Chul Hwang, M.D.*, Hyun Kee Yoon, M.D.*, Eun Sil Yoo, M.D.** Kyu Bo Sung, M.D.*, Yung Sang Lee, M.D., Sung Gyu Lee, M.D.# and Dong Jin Suh, M.D.; Korean J Hepatol 1999;5(3):217-226.

Abstract
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Background/Aims
Transarterial chemoembolization (TACE) has been reported to be one of the useful palliative treatments in patients with unresectable hepatocelluar carcinoma. However, Bile duct injuries following TACE have been reported occasionally. In this study, we intended to clarify the incidence, pathogenic mechanisms and clinical implications of bile duct injuries following TACE. Methods: A total of 950 consecutive patients with hepatocellular carcinoma (HCC) were subjected. 807 patients were treated with TACE. The remaining 143 were treated with transarterial chemoinfusion (TACI) of cisplatin. Results: None of 143 HCC patients treated with TACI revealed to have any ischemic biliary injury radiologically. In contrast, out of 807 with TACE, 17 (2%) appeared to have biliary complications. Twelve out of 17 (71%) had bilomas at subcapsular area, three out of 17 (18%) had focal strictures at common hepatic duct or common bile duct with marked dilatation of intrahepatic bile ducts and two out of 17 (11%) had diffuse mild dilatation of intrahepatic bile ducts. Interestingly, two (17%) out of 12 bilomas were found at the lobe which was not embolized with Gelfoam. The median sessions of TACE to the occurrences of focal strictures tended to be longer compared with those of bilomas (median: 6 vs. 2.5; p=0.08). All three patients with focal strictures and four (33%) out of 12 patients with bilomas were associated with serious bacterial infections at presentation. Conclusions: Biloma seems to be caused by lipiodol rather than Gelfoam; focal strictures of large bile ducts by Gelfoam. It is suggested that adjustments of the amounts of lipiodol or Gelfoam and the sites or embolization may be required to reduce the ischemic biliary injuries following TACE. (Korean J Hepatol 1999;5:217－226)

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Case Report

A Case of Necrotizing Liver Abscess and Bile Duct Necrosis Following Hepatic Arterial Chemoembolization in Hepatocelluar Carcinoma: Gyu Jung, M.D., Jeong Wook Kim, M.D., Sang Jin Kim, M.D. Jun Hyung Joe, M.D., Jong Beum Lee, M.D.§, Jae Gyu Kim, M.D. Joongwon Park, M.D., Sae Kyung Chang, M.D., Byung Cheol Yoo M.D. and Sill Moo Park M.D.; Korean J Hepatol 1999;5(4):348-352.

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Transcatheter arterial chemoembolization (TACE) is widely used in the treatment of hepatocellular carcinomas. We report a case of mult iple liver abscess with bile duct necrosis following gallbladder infarction after TACE in a patient with hepatocellular carcinoma. A 62- year old man, wit h four cm sized hepatocellular carcinoma in right lobe, was treat ed by TACE for six times during 18 months. Two days after the last TACE, acute cholecystitis occurred and antibiotics were used until the recovery of cholecystitis. After two months, abdominal CT scan revealed a gas containing liver abscess and percutaneous transhepatic drainage was performed. Cholangiography via drainage cathet er showed findings of bile duct necrosis. Ant ibiotics sensit ive to the causative organism were administered intravenously. However, the abscess persisted despite of treatment for three mont hs. (Korean J Hepatol 1999 ; 5 : 348－352)

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Liver Imaging

Bile Duct Invasion of Hepatocellular Carcinoma: Joon Koo Han; Korean J Hepatol 2001;7(1):112-114.

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Liver Pathology

Biliary Papillomatosis: Hyun Lyoung Koo,Eun Sil Yu; Korean J Hepatol 2002;8(3):336-339.

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Case Reports

A Case of Vanishing Bile Duct Syndrome Associated with Hypersensitivity to Allopurinol: Seong Ho Choi, M.D., Soo Hyun Yang, M.D., Young Bong Song, M.D., Hye Jin Kim, M.D., Yeoung Tae Seo, M.D., Dong Seog Choi, M.D., Kyoung Hyoub Moon, M.D., Jong Hoon Byun, M.D. and Eun Sil Yu, M.D.1; Korean J Hepatol 2005;11(1):80-85.

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Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome. (Korean J Hepatol 2005;11: 80-85)

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Spontaneous Resolution of Vanishing Bile Duct Syndrome in Hodgkin`s Lymphoma: Woo Sik Han , Eun Suk Jung , Youn Ho Kim , Chung Ho Kim , Sung Chul Park , Ji Yeon Lee , Yun Jung Chang , Jong Eun Yeon , Kwan Soo Byun , Chang Hong Lee; Korean J Hepatol 2005;11(2):164-168.

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Cholestasis in a patient with Hodgkin’s disease is uncommon, and the causes of cholestasis are mainly direct tumor involvement of the liver, hepatotoxic effects of drugs, viral hepatitis, sepsis and opportunistic infections. Vanishing bile duct syndrome (VBDS) represents a very rare cause for cholestasis in this disease. We report here on a case of a 45-year-old man who developed VBDS during the complete remission stage of Hodgkin’s lymphoma. There was no history of hepatitis or intravenous drug abuse, and the patient had negative results for hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. The serological studies for antinuclear antibodies, anti-mitochondrial antibodies and anti-smooth muscle antibodies were also negative. Liver biopsy disclosed the absence of interlobular bile ducts in 9 of 10 portal tracts without any active lymphocyte infiltration and there were no Reed-Sternberg cell in the liver. The patient’s cholestasis was in remission and the serum bililrubin level was normalized after two months without treatment, but tumor recurrence was noted at multiple sites of the abdominal lymph nodes on follow-up abdomino-pelvic computed tomogram. (Korean J Hepatol 2005;11:164-168)

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Liver Pathology

Bile Duct Cystadenocarcinoma: So Young Jin; Korean J Hepatol 2007;13(1):108-111.

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Case Report

Carcinoma with Predominant Lymphoid Stroma in Hepatobiliary System -Report of 2 Cases-: Hye Sook Min , Eun Shin , Ja June Jang; Korean J Hepatol 2007;13(2):222-227.

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Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma with predominant lymphocytic infiltration, which is associated with Epstein-Barr virus (EBV) in variable proportions. We report two cases of carcinoma with predominant lymphoid stroma in hepatobiliary system. The first case was a lymphoepithelioma-like undifferentiated carcinoma with focal differentiation of cholangiocarcinoma (cytokeratin 19+) and hepatocellular carcinoma in light microscopy. The infiltration of CD8+ T lymphocytes was observed in the tumor and the surrounding hepatic parenchyme. In this tumor, EBV was detected and LMP1 was positive immunohistochemically. The second case showed the mixed features of lymphoepithelioma-like carcinoma and cholangiocarcinoma with predominant lymphoid stroma. In this case, EBV was detected. LELC of hepatobiliary system is an entity distinguished from conventional carcinoma with lymphoid stroma, and its association with EBV warrants further research. (Korean J Hepatol 2007;13:222-227)