Mycophenolate Mofetil as Second Line Therapy in Autoimmune Hepatitis?

Hennes, Elke; Oo, Ye Htun; Schramm, Christoph; Denzer, Ulrike W.; Buggisch, Peter; Wiegard, Christiane; Kanzler, Stephan; Schuchmann, Marcus; Boecher, Wulf O.; Galle, Peter R.; Adams, David H.; Lohse, Ansgar W.

doi:10.1111/j.1572-0241.2008.02180.x

Cited by 171 publications

(64 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent retrospective European study confirms this observation and underlines that mycophenolate mofetil is helpful to overcome azathioprine intolerance rather than resistance [18]. However, larger randomized prospective studies are required to evaluate the efficacy of mycophenolate mofetil in induction and maintenance of remission compared to the standard therapy with azathioprine.…”

Section: Alternative Treatment Strategiesmentioning

confidence: 53%

Therapeutic Strategies for Autoimmune Hepatitis

Manns

Strassburg²

2011

Dig Dis

View full text Add to dashboard Cite

Autoimmune hepatitis (AIH) is a disease of unknown etiology. However, a loss of tolerance against the patient’s own liver is regarded as the main pathogenetic mechanism. Immunosuppressive therapy prolongs survival in patients with severe AIH. Two phases of therapy have to be distinguished. In newly diagnosed AIH, induction of remission is the main goal. Here predniso(lo)ne alone or in combination with azathioprine has been shown to induce remission in the majority of patients. In the past, reduction of aminotransferase levels below two times the upper limit of normal was the aim of therapy. Nowadays, normalization of aminotransferase levels should be achieved. The majority of patients usually respond to therapy within 6–12 months. A significant reduction in aminotransferase levels is achieved within a few weeks of therapy. Improvement in clinical symptoms is followed by improvement in biochemical parameters of disease activity and then by significant improvement in histological disease activity. Around 20–40% of patients do not achieve remission. In these patients, alternative therapies should be evaluated for the individual patient. Prospective controlled trials with a larger number of patients are missing in this population. At the moment, mycophenolate mofetil at a dose of 2 × 1 g daily, either given alone or in combination with predniso(lo)ne, is able to achieve remission in a significant proportion of patients. Based on recent retrospective observations, mycophenolate mofetil is beneficial in patients who were previously azathioprine intolerant rather than azathioprine failure patients. Again, prospective trials are missing. Alternative drugs include cyclophosphamide, cyclosporin A, tacrolimus and others. Women in particular suffer from steroid-specific side effects, including weight gain, moon face, diabetes, glaucoma and bone disease. Recently, a topical steroid, budesonide, was shown to induce disease remission in combination with azathioprine. The second phase of therapy is maintenance of remission with the lowest possible dose in order to maintain remission while preventing significant side effects. Careful evaluation of the individual patients should lead to the decision whether predniso(lo)ne, budesonide, azathioprine or a combination of one of the steroids with azathioprine is to be used to maintain remission. Recently, a study has shown that after 6 months of induction therapy with prednisone plus azathioprine, a switch to budesonide in combination with azathioprine reduced steroid-specific side effects while maintaining remission of liver disease. Therefore, the application of the topical steroids may be helpful in maintaining remission while reducing steroid-specific side effects. Patients with liver cirrhosis should not be treated with budesonide since the benefit of budesonide with its 90% pass effect in the liver is lost if the patient has already developed portal hypertension with significant portosystemic shunting. Furthermore, there are safety concerns regarding budesonide use in cirrhotic p...

show abstract

Section: Alternative Treatment Strategiesmentioning

confidence: 53%

Therapeutic Strategies for Autoimmune Hepatitis

Manns

Strassburg²

2011

Dig Dis

View full text Add to dashboard Cite

show abstract

“…In patients intolerant to azathioprine, mycophenolate mofetil seems to be a relatively good alternative [92][93][94]. It appears to be of very limited efficacy in patients with an insufficient response to azathioprine [95], but experience in children is more favorable than in adults [96]. In these patients stronger immunosuppressive agents appear to be required, and good results have been reported with cyclophosphamide [97], methotrexate [98], cyclosporine [99], tacrolimus [94,100] and infliximab [101].…”

Section: Non-responsementioning

confidence: 96%

Autoimmune hepatitis

Lohse¹,

Mieli‐Vergani²

2011

Journal of Hepatology

Self Cite

180

147

View full text Add to dashboard Cite

Autoimmune hepatitis was one of the first liver diseases for which an effective treatment was developed and the benefit proven by randomized controlled trials. Nonetheless, both the diagnosis and the treatment of autoimmune hepatitis remain full of challenges. The clinical spectrum is very wide, ranging from subclinical non-progressive disease to fulminant hepatic failure. Diagnostic criteria based on elevation of IgG, demonstration of characteristic autoantibodies, and histological features of hepatitis in the absence of viral disease are very helpful. However, in some patients, diagnosis remains a clinical challenge. Adequately dosed steroids are the mainstay of remission induction treatment, while remission maintenance is best achieved by azathioprine. Therapeutic alternatives are required in a small group of patients responding insufficiently to these drugs or intolerant to their side effects.

show abstract

“…However, results from a multicentre European study (n = 37) were more sobering, with MMF inducing a biochemical response in only 43% of cases, any benefit largely being restricted to patients intolerant of azathioprine [Hennes et al 2008]. More favourable reports from Greece (n = 59) and the Netherlands (n = 45) found that 67-88% of patients taking MMF as an alternative to azathioprine achieved biochemical remission [Zachou et al 2011;Baven-Pronk et al 2011].…”

Section: Alternative Treatmentsmentioning

confidence: 99%

Treatment of autoimmune liver disease: current and future therapeutic options

Trivedi

Hirschfield

2013

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice.

show abstract

Mycophenolate Mofetil as Second Line Therapy in Autoimmune Hepatitis?

Abstract: In the light of its good tolerability, MMF seems to be an alternative for patients who could not tolerate azathioprine previously. However, our data suggest that a majority of patients fail MMF particularly if they are switched because of an insufficient response to azathioprine.

Cited by 171 publications

References 18 publications

Therapeutic Strategies for Autoimmune Hepatitis

Therapeutic Strategies for Autoimmune Hepatitis

Autoimmune hepatitis

Treatment of autoimmune liver disease: current and future therapeutic options

Contact Info

Product

Resources

About