• IMMUNE NETWORK
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• v.6 no.1
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• pp.20-26
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• 2006

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases arc reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whe ther or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. Methods: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-${\kappa}B$ pathway. Results: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-${\kappa}B$ pathway. Conclusion: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a proinflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.3
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• pp.310-310
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• 2020

• Journal of Yeungnam Medical Science
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• v.18 no.1
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• pp.51-58
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• 2001

Background: Cholestatic hepatitis is failure of bile to reach the duodenum with hepatocellular damage and no demonstable obstruction of the major bile ducts. The prognosis is usually good with recovery in less than 4 weeks after withdrawal of the offending drug. However, a prolonged course lasting over 3 months is possible and, in rare cases, progression to ductopenia with development of a vanishing bile duct syndrome occurs. A differential diagnosis with other causes of Chronic liver disease is needed. Materials and Methods: From January 1991 through January 2000, 14 patients diagnosed as cholestatic hepatitis by liver biopsy were included. The possible causative drug, clinical features, laboratory findings, and progression of cholestatic hepatitis were evaluated. The semiquantitative study of liver lesions was performed by two independent observers. Results: Causes of cholestatic hepatitis are 5 cases of oriental medicine, 3 cases of anti-tuberculosis medication, 1 case of ticlopidine and antibiotics and 4 cases of unknown causes. The clinical features of cholestatic hepatitis were jaundice, itching, urine color change, and general weakness. During 6 to 30 months, LFT of 5 patients showed prolonged elevation. Elevated total cholesterol ${\geq}$250 mg/dL in 6 patients, pheripheral blood eosinophilia in 5 patients, auto-antibody positive in 6 patients were observed respectively. The biopsies showed intralobular bilirubinostasis with a mixed portal inflammatory infiltration. Conclusion: In cholestatic hepatitis, durations of abnormal LFT are variable regardless of causative drugs. If cholestatic hepatitis progresses toward chronic course, viral hepatitis, primary biliary cirrhosis, and autoimmune hepatitis should be differentially diagnosed and sequential liver biopsies are needed.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.46.1-46.16
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• 2023

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gamma-inducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5917-5935
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• 2012

Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.1
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• pp.41-48
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• 2005

Purpose: Non-A, B, C viral hepatitis is the name given to the disease with clinical viral hepatitis, but in which serologic evidence of A, B, C hepatitis has not been found. Little is known about the etiology and clinical features of non-A, B, C viral hepatitis in children. Methods: A clinical analysis of 45 cases with non-A, B, C viral hepatitis who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 2001 to June 2004 was carried out retrospectively. Patients who were positive for HBsAg, anti-HAV and anti-HCV and had toxic, metabolic, autoimmune, or neonatal hepatitis were excluded in this study. Results: Among 45 cases of non-A, B, C viral hepatitis, the etiology was unknown in 26 (57.8%), CMV (cytomegalovirus) in 14 (31.1%), EBV (Epstein Barr virus) in 2 (4.4%), HSV (herpes simplex virus) in 2 (4.4%) and RV (rubella virus) in 1 (2.2%). Twenty seven out of 45 (60.0%) patients were under 1 year of age. Sixteen (33.3%) patients had no specific clinical symptoms and were diagnosed incidentally. On physical examination, twenty seven out of 45 patients (60.0%) had no abnormal findings. Forty three out of 45 patients (95.6%) showed classic clinical course of acute viral hepatitis, whereas fulminant hepatitis developed in two patients. Mean serum ALT (alanine aminotransferase) level was $448.7{\pm}771.9IU/L$. Serum ALT level was normalized in 31 out of 45 patients (81.6%) within 6 months and all patients within 18 months. Aplastic anemia was complicated in a case. Conclusion: Although most patients with non-A, B, C viral hepatitis showed a good prognosis, a careful follow-up would be necessary because some of them had a clinical course of chronic hepatitis, fulminant hepatitis and severe complication such as aplastic anemia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4367-4372
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• 2014

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.318-322
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• 2012

Sarcoidosis is an inflammatory disease involving multiple-organs with an unknown cause. The new onset of sarcoidosis associated with therapeutic agents has been observed in 3 clinical settings; tumor necrosis factor antagonists in autoimmune rheumatologic diseases, interferon alpha with or without ribavirin in patients with chronic hepatitis C or melanoma, and antineoplastic agent-associated sarcoidosis in patients with hematologic malignancies. Here, we report a female patient who developed sarcoidosis after capecitabine treatment as an adjuvant chemotherapy for sigmoid colon cancer. To our knowledge, this is the first report of a capecitabine-induced sarcoidosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.4
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• pp.201-212
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• 2023

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5-204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.16 no.4
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• pp.207-218
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• 2013

Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle.