检索结果-南通市图书馆

Chinese medicine in the treatment of Autoimmune hepatitis:Progress and future opportunities

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Animal Models and Experimental Medicine 2022年第2期5卷 95-107页

作者： Jia Liu Zhi Ma Han Li Xiaojiaoyang Li School of Life Sciences Beijing University of Chinese MedicineBeijingChina

Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease occurring in indi-viduals of all ages with a higher incidence in females and characterized by hypergam-maglobulinemia,elevated serum autoantibodies and histological features of interface hepatitis.AIH pathogenesis remains obscure and still needs in-depth study,which is likely associated with genetic susceptibility and the loss of immune homeostasis.Steroids alone and in combination with other immunosuppressant agents are the pri-mary choices of AIH treatment in the clinic,whereas,in some cases,severe adverse effects and disease relapse may occur.Chinese medicine used for the treatment of AIH has proven its merits over many years and is well tolerated.To better under-stand the pathogenesis of AIH and to evaluate the efficacy of novel therapies,several animal models have been generated to recapitulate the immune microenvironment of patients with AIH.In the current review,we summarize recent advances in the study of animal models for AIH and their application in pharmacological research of Chinese medicine-based therapies and also discuss current limitations.This review aims to provide novel insights into the discovery of Chinese medicine-originated therapies for AIH using cutting-edge animal models.

关键词： animal models Autoimmune hepatitis immune regulation Traditional Chinese medicine

Overlap of concurrent extrahepatic autoimmune diseases is associated with milder disease severity of newly diagnosed Autoimmune hepatitis

在线全文

学校读者我要写书评

暂无评论

Hepatobiliary & Pancreatic Diseases International 2021年第1期20卷 21-27页

作者： Tobias Mühling Helmut Rohrbach Wolfgang Schepp Felix Gundling Department of Gastroenterology Internal Medicine ⅡUniversity of WürzburgWürzburgGermany Department of Pathology Academic Teaching Hospital BogenhausenTechnical University of MunichMunich 81925Germany Department of Gastroenterology Hepatology and Gastrointestinal OncologyAcademic Teaching Hospital BogenhausenTechnical University of MunichMunich 81925Germany Department of Internal Medicine Division of GastroenterologyGastrointestinal Oncology and DiabetologyKemperhof KoblenzKoblenzGermany

Background:Concurrent extrahepatic autoimmune disorders(CEHAID)are frequently observed in Autoimmune hepatitis(AIH).It is not clear whether there is any prognostic significance of CEHAID on AIH.The aim of this study was to examine the prognostic impact of CEHAID and the correlation with the disease severity of AIH.Methods:This study included 65 hospitalized subjects who fulfilled the accepted criteria for AIH during an 8-year period(2009–2016).All records were manually screened for presence of associated autoimmune diseases.Disease severity of AIH was assessed by liver laboratory tests including the ratio of aspartate aminotransferase to alanine aminotransferase(AST/ALT)and liver histology.Results:Among the enrolled patients,52(80%)were female(median age 61 years,IQR 45–75).Fifty-six(86.2%)were classified as type-1 AIH.In 26(40%)patients at least one additional extrahepatic autoimmune disease was diagnosed.Thirty-four subjects were referred to our hospital because of acute presentation of AIH(supposed by an acute elevation of hepatic enzymes)for subsequent liver biopsy resulting in initial diagnosis of AIH.This group was stratified into 3 subgroups:(A)AIH alone(n=14);(B)overlap with primary biliary cirrhosis(PBC)/primary sclerosing cholangitis(PSC)(n=11);and(C)with CEHAID(n=9).AST/ALT ratio was the lowest in subgroup C(median 0.64,IQR 0.51–0.94;P=0.023),compared to subgroup A(median 0.91,IQR 0.66–1.10)and subgroup B(median 1.10,IQR 0.89–1.36).Patients with AIH alone showed a trend to the highest grade of fibrosis(mean 2.3;95%CI:1.5–3.0)with no statistical significance compared to subjects with CEHAID(lowest grade of fibrosis;mean 1.5;95%CI:0.2–2.8;P=0.380)whereas the ongoing inflammation was comparable.Conclusions:AST/ALT ratio and extent of fibrosis were lower in subjects with AIH and CEHAID,compared to subjects with only AIH.Therefore,the occurrence of CEHAID might be a predictor for lower disease severity of newly diagnosed acute onset AIH,possibly caused by an earlier diagnosis or different modes of damage.

关键词： Autoimmune hepatitis Concurrent extrahepatic autoimmune disease Serum aminotransferase activities

Acute onset of Autoimmune hepatitis in children and adolescents

在线全文

学校读者我要写书评

暂无评论

Hepatobiliary & Pancreatic Diseases International 2020年第1期19卷 17-21页

作者： Vratislav Smolka Oksana Tkachyk Jiri Ehrmann Eva Karaskova Martin Zapalka Jana Volejnikova Department of Pediatrics Faculty of Medicine and DentistryPalacky University and University Hospital OlomoucI.P.Pavlova 185/6Olomouc 77900Czech Republic Department of Clinical and Molecular Pathology Faculty of Medicine and DentistryPalacky University and University Hospital OlomoucI.P.Pavlova 185/6Olomouc 77900Czech Republic

Background: Autoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previ- ously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients ful ll criteria for acute liver failure (ALF). Methods: Forty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them ful lled revised diagnostic criteria of the International Autoimmune hepatitis Group (IAIHG) for probable or con rmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). Results: Acute onset of AIH occurred in 19/40 children (48%). Six of them ful lled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previ- ously undiagnosed chronic AIH, among which 4 children were histologically con rmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed signi cantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological ndings in A- AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. Conclusion: Rapid and accurate diagnosis of A-AIH may be di cult. However, timely start of immunosup-pressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.

关键词： Acute liver failure Autoimmune hepatitis Children Onset

Th17/Treg balance and factors related to Autoimmune hepatitis

在线全文

学校读者我要写书评

暂无评论

Rheumatology & Autoimmunity 2022年第4期2卷 221-229页

作者： Miao Xue Junshuai Feng Aimin Yang Liping Gao Xuebin Peng Ni Jiang Xiaorong Mao Department of Rheumatology and Immunology The First Hospital of Lanzhou UniversityLanzhouChina Department of Infectious Diseases Gansu Provincial HospitalLanzhouChina Department of Medicine&Therapeutics The Chinese University of Hong KongHong KongChina Department of Infectious Diseases The First Hospital of Lanzhou UniversityLanzhouChina

Background:Although Th17 cells and regulatory T cells play critical roles in Autoimmune hepatitis,the balance between them in acute and chronic immune hepatitis is not well‐studied.The objective of this study was to explore the role of Th17/Treg balance in Autoimmune hepatitis.Methods:Thirty female Wistar rats were randomly divided into the following three groups:acute model(AC),chronic model(CC),and healthy control(HC).Aspartate aminotransferase,alanine aminotransferase,and bilirubin levels were measured.Peripheral blood interleukin(IL)‐17,IL‐6,IL‐10,and transforming growth factor‐βcytokine levels were also assessed.Flow cytometry was used to detect changes in the Th17 cell and Treg cell frequency,and the Th17/Treg ratio was calculated.Results:The frequency of Th17 cells and Treg cells were both increased(p<0.05)and the Th17/Treg ratio was higher in the AC group compared with those in the HC group(p<0.05).Th17 cell levels were significantly lower and Treg cell levels were significantly higher in the CC group,compared with those in the AC group(p<0.05).In addition,the Th17/Treg ratio was lower in the CC group compared with that in the HC group(p<0.05).Conclusion:The Th17/Treg ratio was increased in the acute immune liver injury model and decreased in the chronic liver injury model.Th17/Treg imbalance may play a critical role in liver injury occurrence and development.

关键词： α‐galcer Autoimmune hepatitis ConA Th17 cells Treg cells

CD4+Foxp3+CD25+/-Tregs characterize liver tissue specimens of patients suffering from drug-induced Autoimmune hepatitis:A clinical-pathological study

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Hepatobiliary & Pancreatic Diseases International 2018年第2期17卷 133-139页

作者： Li-Mei Qu Shu-Hua Wang Kun Yang David R.Brigstock Li Su Run-Ping Gao Department of Hepatic-Biliary-Pancreatic Medicine First Hospital of Jilin UniversityChangchun 130021China Department of Surgical Gastroenterology First Hospital of Jilin UniversityChangchun 130021China The Research Institute at Nationwide Children’s Hospital ColumbusOH 43205USA Division of Pediatric Surgery Department of SurgeryThe Ohio State UniversityColumbusOH 43205USA

Background: The diagnosis of drug-induced Autoimmune hepatitis(DIAIH) and its differentiation from idiopathic Autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4~+Foxp3~+CD25+/-regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4~+Foxp3~+CD25+/-Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4~+Foxp3~+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4~+Foxp3~+CD25~-Tregs compared with AIH(P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4~+Foxp3~+CD25~-Tregs(P < 0.05).However, the frequency of peripheral blood CD4~+Foxp3~+CD25+/-Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4~+Foxp3~+CD25~-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

关键词： Drug-induced liver injury Autoimmune hepatitis Drug-induced Autoimmune hepatitis Liver biopsy Regulatory T cells

Rescue of Autoimmune hepatitis by soluble MHC class II molecules in an altered concanavalin A-induced experimental model

在线全文

学校读者我要写书评

暂无评论

Animal Models and Experimental Medicine 2020年第3期3卷 264-272页

作者： Katerina Bakela Maria Georgia Dimitraki Evangelia Skoufa Irene Athanassakis Laboratory of Immunology Department of BiologyUniversity of CreteHeraklionCreteGreece

Background:Soluble major histocompatibility complex class II(sMHCII)molecules have been described to maintain tolerance through the suppression of autoreactive T lymphocytes.In order to evaluate their ability to rescue Autoimmune hepatitis(AIH)symptoms,the present work attempted to administer sMHCII molecules to an in vitro as well as in vivo concanavalin A(ConA)-induced AIH model.Methods:The in vitro AIH model consisted of splenocyte stimulation with ConA in the presence or absence of serum-isolated sMHCII molecules.An in vivo ConAmodified model with or without sMHCII treatment was developed.The cytokine profile in culture supernatants and serum was tested by ELISA.Cell markers were evaluated by immunofluorescence,while cell proliferation by tritiated thymidine uptake.AIH symptoms were assessed by daily observations for the establishment of a disease severity scoring system and liver histology was evaluated using a biomolecular imager.Results:The presence of sMHCII molecules in the ConA-stimulated cell cultures leads to a significant reduction of cell proliferation.The administration of sMHCII molecules to the ConA-treated animals showed a significant reduction in the levels of IL-2,IL-4,and IL-10,as well as a decrease in the number of spleen CD4+and CD8+cells.Upon development of a scoring system,it was shown that the sMHCII treatment was accompanied by a slower progression of the disease,while rescuing fibrotic liver morphology.Conclusion:The results presented in this study confirm the ability of sMHCII proteins to alleviate Autoimmune hepatitis,possibly highlighting new therapeutic approaches for autoimmune diseases.

关键词： Autoimmune hepatitis cytokines immunosuppression inflammation

Cytotoxic T lymphocyte antigen-4 gene polymorphisms and susceptibility to type 1 Autoimmune hepatitis in the Tunisian population

在线全文

学校读者我要写书评

暂无评论

Genes & Diseases 2018年第3期5卷 256-262页

作者： Marwa Chaouali Agostinho Carvalho Aymen Tezeghdenti Mouna Ben Azaiez Cristina Cunha Ezzeddine Ghazouani Radhia Kochkar Department of Immunology Military Hospital of TunisMontfleury 1008TunisTunisia El Manar University Laboratory of MycologyPathologies and Biomarkers 1092TunisTunisia Life and Health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoCampus de Gualtar 4710-057BragaPortugal ICVS/3B’s-PT Government Associate Laboratory Braga/Guimara˜esPortugal

Genetic factors and gene polymorphisms leading to the onset of autoimmune response in Autoimmune hepatitis(AIH)are still not full elucidated.Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response.We investigated 3 distinct polymorphic sites(t49A>G,CT60 G>A and e318C>T)of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology.A significant positive association with AIH susceptibility was found for the GG genotype in t49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls(28%vs 9%,pZ0.003,ORZ3.93[1.56e9.88]).The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients.CTLA4 genotyping in position318 did not show any statistically significant difference in genotype or allele distribution.The CTLA4 gene polymorphism in position t49 is associated to AIH susceptibility in the Tunisian population.Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.

关键词： Autoimmune hepatitis CTLA4 gene polymorphisms Cytotoxic Tlymphocyte antigen 4

Autoimmune hepatitis-related Cirrhosis： Clinical Features and Effectiveness of Immunosuppressive Treatment in Chinese Patients

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Medical Journal 2016年第20期129卷 2434-2440页

作者： Yan-Ni Li Huan Ma Lu Zhou Jie Zhang Li-Ping Guo Shu-Qian Li Yi-Qi Qian Bang-Mao Wang Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300054China Department of Gastroenterology and Hepatology Hebei Medical University Third HospitalHebei Medical UniversityShijiazhuangHeibei 050051China Department of Preventive Medicine School of Public HealthTianjin Medical UniversityTianjin 300070China

Background：The long-term outcomes of patients with Autoimmune hepatitis （AIH） given the immunosuppressive treatment are considered to be preferable.However,little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment.We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital.Methods：Patients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed.Two-hundred and fourteen patients who were followed up and satisfied the simplified AIH criteria were included in the study.Among these patients,87 presented with cirrhosis when initially diagnosed for AIH.Immunosuppressive treatments were employed in 57 AIH patients who did not present with cirrhosis and 39 patients who presented with cirrhosis.Initial responses to immunosuppressive treatment of patients with and without cirrhosis were analyzed.Independent risk factors were assessed for predicting the prognosis of patients.The t-test and Cox regression statistical analysis were used.Results：In total,96 AIH patients including 39 with cirrhosis and 57 without cirrhosis underwent immunosuppressive therapy.The overall complete remission after initial immunosuppressive treatment was achieved in 81/96 patients （84.4%）,whereas 9/96 （9.4%） achieved incomplete response,and 6/96 （6.3%） occurred treatment failure.Compared to noncirrhotic patients,patients who presented with cirrhosis responded to treatment to a comparable extent regarding complete response （noncirrhosis 50/57 [87.7%] vs.cirrhosis 31/39 [79.5%],P =0.275）,incomplete remission （noncirrhosis 4/57 [7.0%] vs.cirrhosis 5/39 [12.8%],P =0.338）,and treatment failure （noncirrhosis 3/57 [5.3%] vs.cirrhosis 3/39 [7.7%],P =0.629）.Importantly,the remission rate was comparable （54/57 [94.7%] and 36/39 [92.3%],P =0.629） for noncirrhotic and cirrhotic patients after immunosuppressive therapy.Compared to patients who maintained remission （n =19） after drug withdrawal,patients who experienced relapse （n

关键词： Autoimmune hepatitis Immunosuppressive Agents Liver Cirrhosis Treatment Outcome

在线全文

学校读者我要写书评

暂无评论

Autoimmune hepatitis

Frontiers of Medicine 2015年第2期9卷 187-219页

作者： Farhad Sahebjam John M. Vierling Departments of Medicine and Surgery Baylor College of Medicine Baylor-St. Luke's Medical Center Houston TX 77030 USA

Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte- specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased y-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although Autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent Autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to i

关键词： Autoimmune hepatitis autoantibodies diagnosis immunological diseases drug-induced liver injury therapy immunosuppression outcomes hepatocellular carcinoma liver transplantation