• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.4
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• pp.347-350
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• 2018

Drug-induced autoimmune hepatitis (DIAIH) is an increasingly recognized form of drug-induced liver injury that leads to a condition similar to idiopathic autoimmune hepatitis. A number of drugs have been associated with DIAIH, minocycline is one of the most well characterized. Minocycline is a semisynthetic tetracycline antibiotic used in the treatment of acne vulgaris. Minocycline-induced autoimmune hepatitis presents with serologic and histologic features similar to idiopathic autoimmune hepatitis. However, the natural history and outcomes of these two conditions differ significantly. The majority of patients with minocycline-induced autoimmune hepatitis experience complete resolution of symptoms after withdrawal of the medication. Some patients may require a short course of steroids and rarely use of an immunomodulator to achieve resolution of disease. Recurrence of symptoms is rare and typically only occurs with reintroduction of minocycline. It is important for primary care providers to consider minocycline-induced autoimmune hepatitis when liver injury develops during minocycline therapy.

• 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.23 no.2
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• pp.180-187
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• 2020

Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine. Physical examination showed generalized icterus and splenomegaly. The laboratory findings suggested warm-type AHA with cholestatic hepatitis. Liver biopsy revealed giant cell transformation of hepatocytes and moderate lobular inflammation. The patient was successfully treated with four doses of rituximab. Early relapse of hemolytic anemia and hepatitis was observed, which prompted the use of an additional salvage dose of rituximab. He is currently in clinical remission.

• Journal of Haehwa Medicine
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• v.20 no.1
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• pp.11-23
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• 2011

Systemic Lupus Erythematosus(SLE) is an autoimmune disease invading the skin, joint, kidney, intestinal membrane, neurosystem and other organs. SLE is an autoimmune disease characterized by immune dysregulation resulting in the production of antinuclear antibodies(ANA), generation of circulating immune complexes, and activation of the complement system. In Korean medicine, lupus can be classified as acute arthritis, reddish butterfly erythema, asthenic disease, edema and so on. The cause and procedure of the diseases are flourishing noxious heat, excessive fire due to deficiency of yin, blood stasis due to stagnation of qi, internal movement of the liver-wind, congenital deficiency, exhausted vital-qi, which are treated by clearing away heat and cooling the blood, nourshing yin and extinguishing fire, treating flatulence and activating blood circulation, nourishing the blood to expel wind, invigorating the liver and kidney, invigorating qi and replenishing the blood. To experimentally examine the influence of Insam-Buja-Tang (Ginseng & Aconiti Extract, IBT) on the outbreak and development of lupus, lupus induce MRL/MpJ-Faslpr lupus-prone mice model was used. As IBT was orally administrated to a lupus model mouse, various tests such as the weight, urine protein, renal function, Lymph cell test of the spleen, Cytokine expression, histopathological analysis of kideny were performed to see the influence on the kidney and whether it work effectively on the immune function. The main purpose of this study is to evaluate the effect of IBT on MRL/MpJ-Faslpr lupus-prone mice model. The effect of IBT on MRL/MpJ-Faslpr lupus-prone mice that can have autoimmune disease similar to SLE in human was evaluated after IBT per oral in the present study.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.7 no.2
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• pp.186-196
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• 2004

Purpose: Autoimmune hepatitis is a chronic inflammatory liver disease with unknown cause that is characterized by liver histology, circulating autoantibodies and increased levels of immunoglobulin G. Only sporadic reports are available on autoimmune hepatitis in children. The aim of this study was to evaluate the clinical, biochemical, and histological features, and the long-term outcome of autoimmune hepatitis in Korean children. Methods: We reviewed the medical records of 14 children diagnosed as having autoimmune hepatitis at Seoul National University Children's Hospital from 1990 to 2004, and analyzed clinical, biochemical, and histological features, and clinical outcomes. Results: Mean age at diagnosis was 9 years and 11 of the 14 children were female. Six children presented with acute hepatitis-like manifestations. Jaundice and fatigue were the most common symptoms. Other autoimmune diseases accompanied in 6 children. Anti-nuclear antibody was detected in 13 patients and anti-smooth muscle antibody was positive in 8. All 14 patients were type 1 autoimmune hepatitis. The main histologic findings were interface hepatitis, rosette formation, and cirrhosis. Clinical and biochemical features were improved in six patients treated with ursodeoxycholic acid. Eight patients were treated with corticosteroid alone or in combination with azathioprine and five of them are in biochemical remission. Conclusion: Autoimmune hepatitis is an inflammatory liver disease, which has a favorable long-term outcome if it is diagnosed and treated promptly. Therefore, autoimmune hepatitis should be suspected in children with chronic hepatitis of unknown etiology, especially in female patients who show hypergammaglobulinemia or some clinical features of autoimmune disease.

• 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.

• Journal of Yeungnam Medical Science
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• v.35 no.1
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• pp.89-93
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• 2018

Idiopathic non-cirrhotic portal hypertension (INCPH) is a disease with an uncertain etiology consisting of non-cirrhotic portal hypertension and portal pressure increase in the absence of liver cirrhosis. In INCPH, patients exhibit normal liver functions and structures. The factors associated with INCPH include the following: Umbilical/portal pyremia, bacterial diseases, prothrombic states, chronic exposure to arsenic, vinyl chloride monomers, genetic disorders, and autoimmune diseases. Approximately 70% of patients present a history of major variceal bleeding, and treatment relies on the prevention of complications related to portal hypertension. Autoimmune disorders associated with INCPH are mainly systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. To the best of our knowledge, a case of ankylosing spondylitis (AS) associated with INCPH has not been reported thus far. Therfore, we report our experience of a patient with AS accompanied by INCPH, who showed perisplenic varices with patent spleno-portal axis and hepatic veins along with no evidence of cirrhosis on liver biopsy, and provide a brief literature review.

• 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.

• The Journal of Korean Medicine
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• v.22 no.1
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• pp.3-9
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• 2001

In the view of oriental medicine, the liver is the general of the army in its function of protecting against the enemy. So this concept is very closely associated to the immunological function. Its relations with immunological function are as follows. 1. The liver produces most of the proteins and converts them with hepatocytes, composes 80% in total reticuloendothelial system with Kuffer cells & endothelial cells and has typical structure of sinusoidal vessels closely related with the blood system. 2. The liver plays an important role in innate immunity with Kuffer cells as well as with the molecules that the liver produces, related to complementary systems. 3. In the embryonic period, the liver is associated with immune associated cell growth and their maturation. After birth, it is associated with removing old red blood cells and with systematically modulating immune system through hormone metabolism. 4. The liver controls the autoimmune disease resulting from immune complex by removing molecules like immune complex. 5. In the processing of blood 19A from the digestive system, the liver has an important role in protecting the body from unnecessary immune responses. 6. In the oriental medical view, liver plays a major role in the immune function by storing blood and dispersing stagnated hepatoqi with the help of the kidneys and spleen.

• Korean Journal of Transplantation
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• v.31 no.4
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• pp.157-169
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• 2017

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.