Controlled Trial of Prednisone and Azathioprine in Active Chronic Hepatitis

Murray-Lyon, I M; Stern, Robert L.; Williams, Roger

doi:10.1016/s0140-6736(73)92125-9

Cited by 431 publications

(218 citation statements)

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“…[2][3][4][5][6][7] Although steroids have greatly improved the survival of patients with AIH, whether they prevent fibrosis and ultimate progression to cirrhosis is unclear. In addition, corticosteroid therapy is associated with numerous significant toxicities.…”

mentioning

confidence: 99%

Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome

et al. 2005

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Although the natural history of autoimmune hepatitis (AIH) has been characterized, little is known about patients who present asymptomatically. Consequently, whether they require immunosuppressive therapy with its associated complications is unclear. To compare the natural history of asymptomatic AIH with symptomatic AIH, a large cohort of patients from a single center was examined. All patients with a clinical diagnosis of AIH were reassessed using the revised criteria of the International Autoimmune Hepatitis Group. Liver histology, response to therapy, and survival were assessed. Patients asymptomatic at presentation (n ‫؍‬ 31) had lower serum aminotransferase, bilirubin, and immunoglobulin G (IgG) values at baseline. Half of the asymptomatic patients received no therapy, and their survival was no different from that of the total cohort. Ten-year survival was 80.0% (62.5%-97.5%) in the asymptomatic group and 83.8% (75.1%-92.6%) in the symptomatic patients (P ‫؍‬ NS). Survival to liver-related endpoints at 10 years was similar in both groups: 89.5% (

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confidence: 99%

Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome

et al. 2005

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“…They revealed that untreated AIH has a poor prognosis with 5-and 10-year survival rates of 50 and 10%, respectively, whereas treatment with prednisolone is associated with excellent short-and long-term survival [34,35]. Up to 30% of adult patients have histological features of cirrhosis at diagnosis [18,36] and progression of fibrosis can occur in patients with inflammatory activity despite steroid therapy [18].…”

Section: Natural Historymentioning

confidence: 99%

Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management

2010

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Autoimmune hepatitis (AIH), primary biliary cirrhosis, and primary sclerosing cholangitis are the three major autoimmune diseases affecting the liver, and of these three, AIH is the most typical autoimmune disease being characterized by a T-cell-rich infiltrate, raised circulating c-globulins, autoantibodies, HLA associations, and links with other autoimmune diseases. It is the only one, of the three diseases, that responds well to immunosuppressive therapy. AIH is caused by dysregulation of immunoregulatory networks and the consequent emergence of autoreactive T cells that orchestrate a progressive destruction of hepatocytes leading untreated to liver failure. T cells play a major role in the immunopathogenesis, and both CD4? and CD8? T cells are involved together with effector responses mediated by NK cells, cd T cells, and macrophages. A number of triggering factors have been proposed including viruses, xenobiotics, and drugs, but none have been conclusively shown to be involved in pathogenesis.

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“…Kirk et al 1980;Soloway et al 1972]. Initial conflicting results regarding azathioprine [Mackay, 1968;Murray-Lyon et al 1973] were resolved with data demonstrating clear efficacy and a lower side-effect profile compared with corticosteroid monotherapy when azathioprine is used to reduce or replace corticosteroids [Summerskill et al 1975]. After induction of remission, monotherapy with azathioprine is often effective [Stellon et al 1988].…”

Section: Treatment Of Autoimmune Hepatitismentioning

confidence: 99%

Management of patients with difficult autoimmune hepatitis

Parker

Adams

2012

Therap Adv Gastroenterol

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Autoimmune hepatitis (AIH) is characterized by a T-cell rich infiltrate associated with lobular and interface hepatitis, hypergammaglobulinemia and production of autoantibodies. Genetic risk is linked to the HLA particularly DRB1*0301 and DRB1*0401 alleles in North American and European Caucasian populations. It has recently been suggested that functional deficiencies in CD4 + CD25 + CD127 low FOXP3 + regulatory T cells contribute to the breakdown of immune tolerance that results in AIH. Most patients respond to immunosuppressive therapy with corticosteroids and can be maintained in remission by low-dose corticosteroid treatment and/or azathioprine. For those who progress to end-stage disease liver transplantation is an effective treatment although it is associated with recurrence. In the future it is likely that biological therapies will allow more targeted therapy designed to switch the balance to immune regulation and thereby restore immune homeostasis. Although treatment for many cases is relatively straightforward and successful problems are encountered in those who fail to respond to standard treatment, are unable to tolerate it or relapse. In such cases alternative therapies should be considered. In addition treatment is complicated in some patients by comorbidity and special care is required during and after pregnancy. We will discuss the current and future therapeutic options for patients with difficult to treat AIH.

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Controlled Trial of Prednisone and Azathioprine in Active Chronic Hepatitis

Cited by 431 publications

References 13 publications

Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome

Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome

Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management

Management of patients with difficult autoimmune hepatitis

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