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"Necrosis"

Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats
Ki Tae Yoon, Hongqun Liu, Jing Zhang, Sojung Han, Samuel S. Lee
Clin Mol Hepatol 2022;28(2):232-241.
Published online January 5, 2022
DOI: https://doi.org/10.3350/cmh.2021.0141
Background/Aims
Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.
Methods
Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.
Results
Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.
Conclusion
Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Citations

Citations to this article as recorded by  Crossref logo
  • Cirrhotic cardiomyopathy: pathophysiology, assessment, and implications for liver transplantation
    Madeleine Gill, Anoop N. Koshy, Jeyamani Ramachandran, Geoffrey W. McCaughan, Avik Majumdar
    Therapeutic Advances in Gastroenterology.2026;[Epub]     CrossRef
  • Heart failure with preserved ejection fraction beyond the heart: exploring the heart–liver–pancreas axis
    Han Naung Tun, Omar Rahal, Ivan R Figueroa Baez, Omar Santana-Sánchez, Timothy Gardner
    ESC Heart Failure.2026;[Epub]     CrossRef
  • Bile duct ligation impairs function and expression of breast cancer resistance protein in rat blood-retinal barrier mainly due to both the increased ammonia and bilirubin
    Zijin Lin, Runze Wu, Yiting Yang, Mingrui Ji, Xiaodong Liu, Li Liu, Hanyu Yang
    Drug Metabolism and Disposition.2026; 54(5): 100282.     CrossRef
  • Apoptosis in Cardiac Conditions Including Cirrhotic Cardiomyopathy
    Fengxue Yu, Dae Gon Ryu, Ki Tae Yoon, Hongqun Liu, Samuel S. Lee
    International Journal of Molecular Sciences.2025; 26(13): 6423.     CrossRef
  • Cirrhotic Cardiomyopathy: Bridging Hepatic and Cardiac Pathophysiology in the Modern Era
    Dragoș Lupu, Camelia Cornelia Scârneciu, Diana Țînț, Cristina Tudoran
    Journal of Clinical Medicine.2025; 14(17): 5993.     CrossRef
  • Galectin-3: A Multitasking Protein Linking Cardiovascular Diseases, Immune Disorders and Beyond
    Mariarosaria Morello, Gisella Titolo, Saverio D’Elia, Silvia Caiazza, Ettore Luisi, Achille Solimene, Chiara Serpico, Andrea Morello, Francesco Natale, Paolo Golino, Plinio Cirillo, Giovanni Cimmino
    Targets.2025; 3(4): 34.     CrossRef
  • Galectin-3 as a therapeutic target in pulmonary hypertension: Molecular mechanisms, drug development directions, and emerging clinical applications
    Antonín Sedlář, Pavla Bojarová, František Kolář, Vladimír Křen, Lucie Bačáková
    Biomedicine & Pharmacotherapy.2025; 193: 118756.     CrossRef
  • Cardiomyopathy in cirrhosis: From pathophysiology to clinical care
    Hongqun Liu, Jwan A. Naser, Grace Lin, Samuel S. Lee
    JHEP Reports.2024; 6(1): 100911.     CrossRef
  • Cirrhotic cardiomyopathy: Pathogenesis, clinical features, diagnosis, treatment and prognosis
    Francisca Almeida, Alexandra Sousa
    Revista Portuguesa de Cardiologia.2024; 43(4): 203.     CrossRef
  • Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities
    Hongqun Liu, Daegon Ryu, Sangyoun Hwang, Samuel S. Lee
    International Journal of Molecular Sciences.2024; 25(11): 5849.     CrossRef
  • Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy
    Hongqun Liu, Sang-Youn Hwang, Samuel S. Lee
    Pharmaceuticals.2023; 16(7): 978.     CrossRef
  • Chenodeoxycholic Acid Improves Embryo Implantation and Metabolic Health through Modulating Gut Microbiota–Host Metabolites Interaction during Early Pregnancy
    Meixia Chen, Ying Zhao, Haifeng Ji, Lu Li, Hui Liu, Sixin Wang, Dongyan Zhang, Jingdong Yin, Jing Wang, Xin Zhang
    Antioxidants.2023; 13(1): 8.     CrossRef
  • Temporal profile of cerebrospinal fluid galactin-3 and associated cytokine responses after severe traumatic brain injury in patients: a retrospective study
    Melisa Cetin, Ping Yip, Zhou-Hao Liu
    Future Healthcare Journal.2023; 10: S18.     CrossRef
  • Temporal profile of cerebrospinal fluid galactin-3 and associated cytokine responses after severe traumatic brain injury in patients: a retrospective study
    Melisa Cetin, Ping Yip, Wing Sze Leung, Zhou-Hao Liu
    Clinical Medicine.2023; 23(6): 81.     CrossRef
  • Pathogenic Mechanisms Underlying Cirrhotic Cardiomyopathy
    Hongqun Liu, Henry H. Nguyen, Ki Tae Yoon, Samuel S. Lee
    Frontiers in Network Physiology.2022;[Epub]     CrossRef
  • Collagen-binding fibroblast growth factor ameliorates liver fibrosis in murine bile duct ligation injury
    Qiangqiang Shi, Susu Wei, Zhi Chao Li, Jing Xu, Yaxin Li, Chuanlong Guo, Xianggen Wu, Chunying Shi, Guohu Di
    Journal of Biomaterials Applications.2022; 37(5): 918.     CrossRef
  • 9,613 View
  • 142 Download
  • 11 Web of Science
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Editorial

Liver fibrosis, cirrhosis, and portal hypertension

Leaky gut-derived tumor necrosis factor-α causes sarcopenia in patients with liver cirrhosis
Takumi Kawaguchi, Takuji Torimura
Clin Mol Hepatol 2022;28(2):177-180.
Published online August 26, 2021
DOI: https://doi.org/10.3350/cmh.2021.0246

Citations

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  • Decoding the mechanistic basis of liver–muscle communication in health and disease
    Noha M. Gamil, Habiba A. Elsayed, Esraa T. Salah, Heba A. Mostafa, Riham A. El-Shiekh, Heba R. Ghaiad, Hebatollah E. Eitah
    Naunyn-Schmiedeberg's Archives of Pharmacology.2026;[Epub]     CrossRef
  • Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma
    Toru Nakamura, Atsutaka Masuda, Dan Nakano, Keisuke Amano, Tomoya Sano, Masahito Nakano, Takumi Kawaguchi
    Cells.2025; 14(6): 428.     CrossRef
  • The Impact of Rifaximin on Hepatic Encephalopathy during Lenvatinib Therapy in Patients with Hepatocellular Carcinoma and Splenorenal Shunt
    Shigeo Shimose, Hideki Iwamoto, Takashi Niizeki, Tomotake Shirono, Etsuko Moriyama, Takumi Kawaguchi
    Internal Medicine.2025;[Epub]     CrossRef
  • Metabolic dysfunction-associated fatty liver disease is a ubiquitous latent cofactor in viral- and alcoholic-related hepatocellular carcinoma: Editorial on “Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular c
    Toru Nakamura, Masahito Nakano, Tsubasa Tsutsumi, Keisuke Amano, Takumi Kawaguchi
    Clinical and Molecular Hepatology.2024; 30(4): 705.     CrossRef
  • Interaction between sarcopenia and nonalcoholic fatty liver disease
    Sae Kyung Joo, Won Kim
    Clinical and Molecular Hepatology.2023; 29(Suppl): S68.     CrossRef
  • An ultrasensitive photoelectrochemical assay for tumor necrosis factor-alpha based on hollow CdS cubes as a signal generator and NiCo2O4-Au as a signal extinguisher
    Yamin Fu, Baohuan Fan, Shenzhen Chang, Dongyu Guo, Fuxiang Wang, Qinhe Pan
    The Analyst.2023; 148(19): 4746.     CrossRef
  • Role of increased intestinal permeability in the development and progression of liver diseases
    S. N. Mekhtiyev, O. A. Mekhtiyeva, O. M. Berko, A. M. Kolodkin
    Experimental and Clinical Gastroenterology.2023; (12): 130.     CrossRef
  • 9,597 View
  • 198 Download
  • 7 Web of Science
  • Crossref

Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Association between serum tumor necrosis factor-α and sarcopenia in liver cirrhosis
Ji Won Han, Da In Kim, Hee Chul Nam, U Im Chang, Jin Mo Yang, Do Seon Song
Clin Mol Hepatol 2022;28(2):219-231.
Published online July 20, 2021
DOI: https://doi.org/10.3350/cmh.2021.0082
Background/Aims
Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.
Methods
Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.
Results
LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.
Conclusions
These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Citations

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    Clinical and Molecular Hepatology.2023; 29(Suppl): S68.     CrossRef
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    Current Opinion in Gastroenterology.2023; 39(3): 131.     CrossRef
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    Takumi Kawaguchi, Takuji Torimura
    Clinical and Molecular Hepatology.2022; 28(2): 177.     CrossRef
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  • 365 Download
  • 31 Web of Science
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Liver Imaging

Drug induced liver injury

Chemotherapy induced liver abnormalities: an imaging perspective
Ankush Sharma, Roozbeh Houshyar, Priya Bhosale, Joon-Il Choi, Rajesh Gulati, Chandana Lall
Clin Mol Hepatol 2014;20(3):317-326.
Published online September 25, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.3.317

Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.

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Case Reports

Liver fibrosis, cirrhosis, and portal hypertension

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome
Hae Rim Kim, Young Sun Lee, Hyung Joon Yim, Hyun Joo Lee, Ja Young Ryu, Hyun Jung Lee, Eileen L. Yoon, Sun Jae Lee, Jong Jin Hyun, Sung Woo Jung, Ja Seol Koo, Rok Sun Choung, Sang Woo Lee, Jai Hyun Choi
Clin Mol Hepatol 2013;19(4):417-420.
Published online December 28, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.4.417

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

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  • Terlipressin

    Reactions Weekly.2014; 1523(1): 178.     CrossRef
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  • Crossref
A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with hilar cholangiocarcinoma
Jung Ho Kim, Eul Sik Jung, Seok Hoo Jeong, Ju Seung Kim, Yang Suh Ku, Ki Baik Hahm, Ju Hyun Kim, Yeon Suk Kim
Korean J Hepatol 2012;18(1):94-97.
Published online March 22, 2012
DOI: https://doi.org/10.3350/kjhep.2012.18.1.94

An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patient's condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma.

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    Ippei Yamana, Tomoaki Noritomi, Shinsuke Takeno, Tatsuya Hashimoto, Keisuke Sato, Hideki Shimaoka, Ryosuke Yamaguchi, Fumiaki Ishii, Teppei Yamada, Yuichi Yamashita
    Case Reports in Gastroenterology.2015; 9(3): 361.     CrossRef
  • Antitoxin treatment for liver abscess caused byClostridium perfringens
    Toru Hifumi, Yuichi Koido, Motohide Takahashi, Akihiko Yamamoto
    Clinical and Molecular Hepatology.2013; 19(1): 97.     CrossRef
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Liver Pathology

Massive hepatic necrosis with large regenerative nodules
Haeryoung Kim, Young Nyun Park
Korean J Hepatol 2010;16(3):334-337.
Published online September 30, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.3.334

Citations

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  • Human liver regeneration following massive hepatic necrosis: Two distinct patterns
    Katalin Dezső, Péter Nagy, Sándor Paku
    Journal of Gastroenterology and Hepatology.2020; 35(1): 124.     CrossRef
  • Interpretation of core biopsy of liver mass lesions: A comparison study between cytopathologist and gastrointestinal pathologist
    Erik R. Washburn, Zhaohai Yang
    Annals of Diagnostic Pathology.2019; 40: 152.     CrossRef
  • Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure
    Miriam Bittel, Andreas E. Kremer, Michael Stürzl, Stefan Wirtz, Iris Stolzer, Markus F. Neurath, Gianna Ballon, Claudia Günther
    Cell Death & Disease.2019;[Epub]     CrossRef
  • 10,504 View
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Original Article

Tumor Necrosis Factor-α and Interleukin-6 in Ascitic Fluid and Plasma in Spontaneous Bacterial Peritonitis
Moo In Park,Byung Cheol Song,Soo Hyun Yang,Han Chu Lee,Young Hwa Chung,Yung Sang Lee,Dong Jin Suh
Korean J Hepatol 1999;5(4):314-321.
Background/Aims
Spontaneous bacterial peritonitis (SBP) is a major problem associated with liver cirrhosis which has high mortality. Increased production of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) may be associated with development of renal impairment, one of the most important prognostic parameters in SBP. The aim of this study is to investigate the changes of these cytokines in ascitic fluid and plasma in patients with SBP and the relationship between these cytokines and development of renal impairment. Methods: Forty patients with liver cirrhosis and ascites were studied 21 with SBP and 19 with sterile ascites. TNF-α and IL-6 levels in ascitic fluid and plasma were determined by ELISA at the time of diagnosis in both groups and 48 hours after antibiotics treatment in SBP patients. Results: TNF- and IL-6 levels in ascitic fluid and plasma were significantly higher in patients with SBP than those without SBP (ascitic fluid TNF-α: 2.5±0.5 vs. 1.6±0.2; plasma TNF-α: 2.3±0.5 vs. 1.5±0.2; ascitic fluid IL-6: 3.8±0.5 vs. 3.0±0.4; plasma IL-6: 3.4±0.5 vs. 2.3±0.3, log pg/mL) (p<0.001). In patients with SBP, levels of TNF-α and IL-6 in ascitic fluid and plasma decreased 48 hours after antibiotics treatment. Eleven patients with SBP (11/21, 52%) developed renal impairment. Patients with renal impairment had significantly higher ascitic fluid and plasma TNF-α levels than those without renal impairment (median 2.5 vs. 2.1 for ascitic fluid, p=0.006; median 2.4 vs. 2.0, log pg/mL for plasma, p=0.04). Although four out of eleven (36%) patients who developed renal impairment died during hospitalization, all the patients without renal impairment survived (p=0.09). Conclusion: Our results suggest that the levels of TNF-α and IL-6 in ascitic fluid and plasma are increased in SBP and elevated levels of TNF-α in ascitic fluid and plasma may be associated with development of renal impairment, thus indicating poor prognosis in patients with SBP. (Korean J Hepatol 1999;5:314-321)
  • 2,819 View
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Case Reports

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.
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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A Case of Spontaneous Necm4 of Hepatoellular Carcinoma after Development of Pneumonia
Sihoon Lee, M.D., Cheol Kim, M.D., Sang Chul Lee, M.D., Sung Eun Kim, M.D.*, Young Nyun Park, M.D.*, Kun Hoon Song M.D., Kwang-Hyub Han, M.D., Chae Yoon Chon, M.D., and Young Myoung Moon M.D.
Korean J Hepatol 2001;7(3):330-335.
Spontaneous regression of hepatocellular carcinoma is an extraordinarily rare phenomenon. Fewer than 20 occasions have been reported in the English medical literature. There have only been 5 case reports in Korea. Understanding of the mechanism of spontaneous regression of hepatocellular carcinoma will help us to establish new treatments for the disease. In this case report, we present a 53 year-old Asian male who showed spontaneous necrosis of hepatocellular carcinoma confirmed with pathology. He developed a febrile condition secondary to pneumonia for 2 weeks. After that hepatocellular carcinoma was observed to have been necrosed on an MRI scan and hepatic angiography. A right lobectomy of the liver was done because the possibility of residual microscopic cancer cells could not be ruled out. The pathologic finding confirmed the spontaneous near-total necrosis of hepatocellular carcinoma. The patient has recovered uneventfully and has been followed up for 7 months.(Korean J Hepatol 2001;7:330-335)
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Liver Imaging

Spontaneous Total Necrosis of Hepatocellular Carcinoma
Joon Koo Han, M.D. and Se Hyung Kim, M.D.
Korean J Hepatol 2005;11(4):396-398.
  • 2,735 View
  • 17 Download
Case Report
Black Esophagus Associated with Alcohol Abuse
Jae Won Hong , Seung Up Kim , Ha Na Park , Ju Hee Seo , Yong Chan Lee , Ho Guen Kim
Korean J Hepatol 2008;12(2):133-135.
Black esophagus is a rare condition of the esophagus that manifests as endoscopic findings of black-colored esophageal mucosa, which is usually caused by acute esophageal necrosis. We report a case of alcoholic patient who developed black esophagus. The 85-yearold man was admitted to Severance Hospital due to copious hematemesis over 2 days. Upper gastrointestinal endoscopy showed black-colored mucosa in the distal esophagus. Endoscopic biopsies of the esophagus revealed necrotic tissue, without any viable cells. Follow-up upper gastrointestinal endoscopy performed after supportive care with a proton-pump inhibitor, sucralfate, and total parenteral nutrition resulted in the remarkable healing of the esophageal wall with no complications.
  • 2,794 View
  • 10 Download