• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.155-158
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• 2019

Imatinib mesylate is currently used as the first-line treatment for metastatic gastrointestinal stromal tumors (GISTs). Imatinib-induced hepatotoxicity in patients with GIST is very rare. Its features vary from subclinical elevation of serum aminotransferase to clinically apparent acute hepatitis, which is associated with immunologic reactions. Imatinib-induced hepatotoxicity with autoimmune-like features can be treated by the discontinuation of imatinib mesylate and the administration of oral steroids. Here, we report a case of late-onset imatinib-induced hepatitis with autoimmune-like features in a patient with metastatic GIST, which was improved by oral corticosteroids.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.16 no.1
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• pp.61-64
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• 2013

Infection-induced acute hepatitis complicated with acute pancreatitis is associated with hepatitis A virus, hepatitis B virus or hepatitis E virus. Although rare, Epstein-Barr virus (EBV) infection should be considered also in the differential diagnosis if the patient has acute hepatitis combined with pancreatitis. We report a case of EBV infection with cholestatic hepatitis and pancreatitis with review of literature. An 11-year-old female was admitted due to 1-day history of abdominal pain and vomiting without any clinical symptoms of infectious mononucleosis. Diagnosis of reactivated EBV infection was made by the positive result of viral capsid antigen (VCA) IgM, VCA IgG, Epstein-Barr nuclear antigen and heterophile antibody test. We performed serologic tests and magnetic resonance cholangiopancreatography to exclude other viral or bacterial infection, autoimmune disorder, and structural problems. The patient's symptoms recovered rapidly and blood chemistry returned to normal with conservative treatment similar to previously reported cases.

• The Journal of the Korean life insurance medical association
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• v.11
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• pp.1-4
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• 1992

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.2
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• pp.154-163
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• 2021

Purpose: In children overlap of autoimmune hepatitis (AIH) and primary sclerosing cholangitis is labelled as autoimmune sclerosing cholangitis (ASC). The only prospective pediatric study showed a high prevalence of ASC by using endoscopic retrograde cholangiopancreatography. Aims of our study were to find the prevalence of ASC by using magnetic resonance cholangiography (MRC) in AIH and in non-AIH cirrhosis and to compare clinical presentation and outcome of AIH and ASC. Methods: Prospectively we did MRC in 38 children with AIH (cases) and 19 disease controls (Wilson disease). Multiple biliary strictures with proximal dilatation on MRC were taken as definitive changes of ASC. Detail clinical, laboratory parameters, liver histopathology and treatment outcome were recorded. Results: The median age of cases was 11.5 (3-18) years, 22 (57.9%) were girls and 28 (73.7%) were diagnosed as type 1 AIH. MRC was done in 11 children (28.9%) at the time of diagnosis and in 27 (71.1%) after a median follow-up of 2.5 (0.3-10) years. Abnormal MRC changes were seen in 14/38 (36.8%) of AIH and 8/19 (42.1%) of controls. However, definite changes of ASC were present in four (10.5%) children in AIH and none in controls. None of the clinical, laboratory, histological parameters and treatment response were significantly different between ASC and AIH groups. Conclusion: The prevalence of ASC in children with AIH was just 10.5%. We suggest MRC in select group with cholestatic features, inflammatory bowel disease and in those who showed poor response to immunosuppression instead of all children with AIH.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.2
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• pp.118-126
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• 2018

Purpose: Classical criteria for diagnosis of autoimmune hepatitis (AIH) are intended as research tool and are difficult to apply at patient's bedside. We aimed to study the accuracy of simplified criteria and the concordance with the expert diagnosis based on the original criteria. Methods: A cohort of children under study for liver disorder was selected through consecutive sampling to obtain the prevalence of AIH within the group of differential diagnoses. AIH was defined, based on classical criteria, through committee review of medical reports. Validity indicators of the simplified criteria were obtained in an intention to diagnose approach. Optimal cut-off and the area under the receiver operating characteristic (ROC) curve were calculated. Results: Out of 212 cases reviewed, 47.2% were AIH. For the optimal cut-off (6 points), the simplified criteria showed a sensitivity of 72.0% and a specificity of 96.4%, with a 94.7% positive and a 79.4% negative predictive value. The area under the ROC curve was 94.3%. There was a good agreement in the pre-treatment concordance between the classical and the simplified criteria (kappa index, 0.775). Conclusion: Simplified criteria provide a moderate sensitivity for the diagnosis of AIH, but may help in indicating treatment in cases under suspicion with 6 or more points.

• The Journal of Internal Korean Medicine
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• v.37 no.3
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• pp.560-567
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• 2016

Objectives: The medical records, including laboratory test results, of a patient with autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome were reviewed to observe changes in steroid-induced adverse reactions before and after herbal medicine treatment.Methods: We investigated the records of a 44-year-old female patient with AIH-PBC overlap syndrome treated at the Kyung Hee University Korean Medicine Hospital. Injinchunggan-tang and its modified decoctions were administered, and any changes inclinical manifestations as well as laboratory test results were monitored.Results and Conclusions: Significant decreases in ALP, GGT, ALT, and AST levels were observed after oral administration of the herbal medicines. Improvements in steroid-induced symptoms (hyperglycemia, fatigue, and moon face) were also observed. Injinchunggan-tang and its modified prescriptions are promising candidates for proper management of AIH-PBC overlap syndrome.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.1
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• pp.63-71
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• 2020

Purpose: Autoimmune hepatitis (AIH) is a chronic disease that may lead to cirrhosis. The immunopathogenesis of AIH is not fully understood and it mainly involves T-cell mediated mechanism. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that promotes T cell response and its polymorphism may serve as a severity marker of AIH. No previous study has considered investigating MIF polymorphism in children with AIH. Methods: Forty-two children with definite diagnosis of AIH were enrolled along with 100 age and sex matched controls. All participants were tested for polymorphism at -173GC (rs755622) of MIF gene. All patients received the standard protocol of steroid plus azathioprine to achieve remission. Liver biopsy was performed at time of diagnosis for all patients and only 18 of them underwent a second biopsy after treatment. Results: No statistically significant differences in the frequency of the genotypes GG and GC or in allele distribution were found in both patient and control groups (p=0.590, 0.640 respectively). Initial alanine aminotransferase (ALT) levels at the time of presentation was significantly higher in the GC group than GG group (p=0.020). GC genotype significantly correlated with disease relapse (r=0.41, p=0.007). Regression of necroinflammation and the fibrosis score in the second liver biopsy was statistically significant in the GG group (p<0.0001, p=0.010 respectively). Conclusion: MIF -173GC polymorphism is associated with clinically significant markers of pediatric AIH, including increased initial serum ALT levels, may help predict necroinflammatory/fibrosis regression effectively, following immunosuppressive treatment.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.91-99
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• 2012

Purpose: The aims of this study was to compare and evaluate the clinical characteristics, laboratory data, and prognosis for infants under age 1 year with CMV hepatitis and those with viral hepatitis of unknown etiology. Methods: A retrospective study was conducted of infants under age 1 year who were admitted with acute hepatitis. The exclusion criteria consisted of: autoimmune, genetic, metabolic, toxic, HAV, HBV, HCV, toxoplasma, rubella, herpes simplex, and Epstein-Barr virus. The 30 patients included were divided into two groups based on markers for CMV (IgM anti-CMV, CMV PCR in urine, CMV culture in urine). Results: The median age of patients (n=15) was 2.8 months. No other organ involvement was detected in any patient. Peak serum total bilirubin levels (n=4) ranged from 2.6 to 6.7 mg/dL. Peak serum ALT levels ranged from 51 to 1,581 IU/L. The duration of ALT elevation ranged from 1.5 weeks to 26 weeks (median 9 weeks). All had recovered in full without ganciclovir; there were no cases of hearing loss. The median age of controls (n=15) was 2.5 months. Peak serum total bilirubin levels (n=4) ranged from 1.6 to 9.1 mg/dL. Peak serum ALT levels ranged from 26 to 1,794 IU/L. No significant differences were observed between both groups regarding the peak serum ALT levels, peak serum total bilirubin levels, duration of hyperbilirubinemia and ALT elevation. Conclusion: Although it was not possible to differentiate congenital infection with perinatal infection in this study, the prognosis of patients with CMV hepatitis without other organ involvement was good without ganciclovir treatment.

• Molecules and Cells
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• v.42 no.12
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• pp.906-918
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• 2019

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

• Clinical and Experimental Pediatrics
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• v.63 no.2
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• pp.52-55
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• 2020

Background: Immunomodulatory properties of interferon (IFN) have been documented. It may induce autoimmune diseases such as autoimmune thyroiditis with hypo- or hyperthyroidism. In addition, it may impair thyroid hormone synthesis through affecting iodide organification in thyroid gland. Purpose: The aim of this study was to describe thyroid function tests disturbances in children with chronic hepatitis C (CHC) receiving pegylated interferon-alpha (PEG IFN-α) plus ribavirin. Methods: Fifty children with CHC virus infection who received combined pegylated interferon-alpha with ribavirin were selected. Other 50 apparently healthy children of matched age and sex (considered as control group) were selected. All children (100) were subject to liver function tests, virological studies, and follow-up of thyroid function test during and after the treatment course. Results: Our study showed that 28% of children received combined PEG IFN-α plus ribavirin showed subclinical hypothyroidism. After 24 weeks treatment with combined therapy of IFN plus ribavirin, the mean level of thyroid stimulating hormone (TSH) was 3.23±88 mU/mL, while TSH was 1.16±0.77 mU/mL before starting treatment. On the other hand, mean TSH was 1.09±0.92 mU/mL in normal control group. Conclusion: This study revealed an association between subclinical thyroid dysfunction and treatment with IFN-alpha and ribavirin in children. Further studies on larger number of patients and longer follow-up duration are recommended for further confirmation.