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自身免疫性肝炎抗酵母菌抗体出现的频率和意义

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世界核心医学期刊文摘（胃肠病学分册） 2005年第1期1卷 6-7页

作者： czaja a.j. Shums Z. Donaldson P.T. Norman G.L. 陈云茹 Mayo Clinic 200 First Street S.W. Rochester MN55905 United States

Our aims were to determine the frequency of antibodies to Saccharomyces cerevisiae in autoimmune hepatitis and assess associations with concurrent mucosal diseases, genetic factors,and corticosteroid response. Seropositivity was determined by enzyme immunoassay in 385 samples obtained from 178 *** to Saccharomyces cerevisiae were detected in 49 patients (28% ), and serum levels of immunoglobulin A were higher in seropositive patients (410 ± 35 versus 321 ± 20 mg/dL; P=0.02). Individuals with and without antibodies were not otherwise distinguished by concurrent mucosal diseases, laboratory findings, or outcomes. Antibodies to tissue transglutaminase occurred more commonly in seropositive patients (16 versus 4% ; P=0.008), but this association was lost when corroborating serological criteria for celiac disease were sought. We conclude that antibodies to Saccharomyces cerevisiae are common in autoimmune hepatitis. They may be associated with non-disease-specific immune responses, but they do not define individuals with a distinctive clinical phenotype,associated mucosal diseases, or treatment outcome.

关键词：自身免疫性肝炎酶免疫法乳糜泻血清阳性率血清学阳性黏膜病血清免疫球蛋白份样谷氨酰胺转移酶疾病特异性

自身免疫性肝炎患者对硫唑嘌呤的耐受不良与硫代嘌呤甲基转移酶缺乏有关

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世界核心医学期刊文摘（胃肠病学分册） 2006年第12期2卷 5-5页

作者： czaja a.j. Carpenter H.A. 陈瑜 Mayo Clinic 200 First Street S.W.RochesterMN 55905United States Dr

Thiopurine methyltransferase deficiency has been associated with intolerance to *** goals were to assess the frequency of enzyme deficiency in autoimmune hepatitis and correlate deficiency states with azathioprine ***-six patients receiving azathioprine(50-150 mg daily) were evaluated for enzyme activity and azathioprine-related *** findings were compared to 89 similarly treated but untested *** patients(15%) had low thiopurine methyltransferase levels(11.4± 0.9 U/ml RBC;range,3.5-14.9 U/ml RBC) .Azathioprine intolerance occurred as commonly in patients with normal or above normal enzyme levels as in patients with below normal levels(12% versus 15%,p = 0.7) .Patients treated without enzyme testing had the same frequency of complications(9% versus 13%,p = 0.5) as tested *** conclude that routine screening of blood thiopurine methyltransferase levels has a low yield for identifying individual patients at risk for azathioprine toxicity during conventional low dose therapy for autoimmune hepatitis.

关键词：自身免疫性肝炎硫唑嘌呤甲基转移酶酶水平酶缺乏酶活性

Error field penetration in j-TEXT tokamak based on two-fluid drift-MHD model

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Chinese Physics B 2024年第4期33卷 545-551页

作者：王文徐涛张仪 the j-TEXT team State Key Laboratory of Advanced Electromagnetic Technology International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma PhysicsSchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074China

An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant *** have studied the plasma responses using Fitzpatrick's improved two-fluid model and program *** calculated the error field penetration threshold for *** addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration ***,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the *** scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency ***,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.

关键词： plasma responses drift-MHD model error field penetration

Difficult treatment decisions in autoimmune hepatitis

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World journal of Gastroenterology 2010年第8期16卷 934-947页

作者： Albert j czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine

Treatment decisions in autoimmune hepatitis are complicated by the diversity of its clinical presentations,uncertainties about its natural history,evolving opinions regarding treatment end points,varied nature of refractory disease,and plethora of alternative immu-nosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in au-toimmune hepatitis were identifi ed by Medline search up to October 2009 and 32 years of personal experi-ence. Autoimmune hepatitis may have an acute severe presentation,mild in? ammatory activity,lack autoan-tibodies,exhibit atypical histological changes (centri-lobular zone 3 necrosis or bile duct injury),or have variant features reminiscent of another disease (overlap syndrome). Corticosteroid therapy must be instituted early,applied despite the absence of symptoms,or modified in an individualized fashion. Pursuit of normal liver tests and tissue is the ideal treatment end point,but this objective must be tempered against the risk of side effects. Relapse after treatment withdrawal requires long-term maintenance therapy,preferably with azathioprine. Treatment failure or an incomplete response warrants salvage therapy that can include conventional medications in modified dose or empiricaltherapies with calcineurin inhibitors or mycophenolate mofetil. Liver transplantation supersedes empirical drug therapy in decompensated patients. Elderly and pregnant patients warrant treatment modifications. Difficult treatment decisions in autoimmune hepatitis can be simplified by recognizing its diverse manifestations and individualizing treatment,pursuing realistic goals,applying appropriate salvage regimens,and identifying problematic patients early.

关键词： Autoimmune hepatitis Fulminant hepatitis Salvage therapy Treatment end points

Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions

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World journal of Gastroenterology 2019年第45期25卷 6579-6606页

作者： Albert j czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine and Science

BACKGROUND Multiple pathogenic mechanisms have been implicated in autoimmune hepatitis,but they have not fully explained susceptibility,triggering events,and maintenance or escalation of the ***,they have not identified a critical defect that can be *** goals of this review are to examine the diverse pathogenic mechanisms that have been considered in autoimmune hepatitis,indicate investigational opportunities to validate their contribution,and suggest interventions that might evolve to modify their *** abstracts were identified in PubMed by multiple search *** length articles were selected for review,and secondary and tertiary bibliographies were *** and epigenetic factors can affect susceptibility by influencing the expression of immune regulatory *** dysfunction,possibly related to deficient production of programmed cell death protein-1,can allow autoreactive T cells to escape deletion,and alterations in the intestinal microbiome may help overcome immune tolerance and affect gender *** factors may trigger the disease or induce epigenetic changes in gene *** mimicry,epitope spread,bystander activation,neo-antigen production,lymphocytic polyspecificity,and disturbances in immune inhibitory mechanisms may maintain or escalate the *** that modify epigenetic effects on gene expression,alter intestinal dysbiosis,eliminate deleterious environmental factors,and target critical pathogenic mechanisms are therapeutic possibilities that might reduce risk,individualize management,and improve *** conclusion,diverse pathogenic mechanisms have been implicated in autoimmune hepatitis,and they may identify a critical factor or sequence that can be validated and used to direct future management and preventive strategies.

关键词： Autoimmune hepatitis Pathogenesis Epigenetics Molecular mimicry Epitope spread Intestinal microbiome

Hepatic inflammation and progressive liver fibrosis in chronic liver disease

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World journal of Gastroenterology 2014年第10期20卷 2515-2532页

作者： Albert j czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester MN 55905 United States

Chronic liver inflammation drives hepatic fibrosis,and current immunosuppressive,anti-inflammatory,and anti-viral therapies can weaken this *** fibrosis is reversed,stabilized,or prevented in 57%-79%of patients by conventional treatment regimens,mainly by their anti-inflammatory ***,however,are commonly incomplete and inconsistently *** fibrotic mechanisms associated with liver inflammation have been clarified,and anti-fibrotic agents promise to improve outcomes as a.j.nctive *** C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within *** can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen ***-oxidants(Nacetylcysteine,S-adenosyl-L-methionine,and vitamin E)and angiotensin inhibitors(losartin)have had antifibrotic actions in preliminary human studies,and they may emerge as supplemental ***-fibrotic agents presage a new era of supplemental treatment for chronic liver disease.

关键词： Inflammation Fibrosis Cirrhosis Treatment Anti-oxidants Angiotensin receptors Investigational drugs

Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

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World journal of Gastroenterology 2016年第42期22卷 9257-9278页

作者： Albert j czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine

The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora(dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens(molecular mimicry). Activated gutderived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as a.j.nctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.

关键词： Intestinal microbiome Inflammasomes Autoimmune hepatitis Dysbiosis Toll-like receptors

Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

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World journal of Gastroenterology 2021年第25期27卷 3705-3733页

作者： Albert j czaja Department of Medicine Mayo Clinic College of Medicine and ScienceRochesterMN 55905United States

Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic *** goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic *** abstracts were identified in PubMed by multiple search terms,and bibliographies were *** cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory *** pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells *** MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver *** phenotype lacks disease-specificity,and it does not predict the biological *** cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated *** have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary *** factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual *** manipulations of function are warranted to establish an association with disease severity and *** conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and *** pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.

关键词： Innate-like lymphocytes Antimicrobial Immune regulatory Pathogenic Mucosal-associated invariant T cell

Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment

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World journal of Gastroenterology 2009年第19期15卷 2314-2328页

作者： Albert j czaja Yusuf Bayraktar Division of Gastroenterology and Hepatology Mayo Clinic College of MedicineRochesterMinnesotaUnited States and the Department of GastroenterologyHacettepe University School of MedicineAnkara 06100Turkey

Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected throuqh Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis. Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long- term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies,and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.

关键词： Non-classical phenotypes Scoring systems Treatment strategies