Relapse Following Treatment Withdrawal in Patients with Autoimmune Chronic Active Hepatitis

Hegarty, John E.; Aria, K T Nouri; Portmann, Bernard; Eddleston, A. L. W. F.; Williams, Roger

doi:10.1002/hep.1840030510

Cited by 164 publications

(89 citation statements)

References 12 publications

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“…In a randomized controlled trial, budesonide has recently been shown to be as effective as prednisolone, with fewer side effects (23). Although induction of remission was successful in a substantial percentage of patients, relapse was quite common, ranging from 30% after 6 months to 70% after 2-3 years of follow-up (24,25). An important finding in our study was that decreasing AST/ALT levels to less than 30 IU/L for men and less than 19 IU/L for women (instead of reducing AST/ALT levels to less than twice the normal value reported by the laboratory) lessened the risk of relapse.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Long Term Outcome of 102 Treated Autoimmune Hepatitis Patients

et al. 2012

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Article type: Original ArticleBackground: There is limited data on the natural history of autoimmune hepatitis (AIH) and on the long-term follow-up of AIH patients who have been referred for regular medical attention. Objectives: We evaluated the clinical presentation and natural history of AIH in a large cohort of type I AIH patients from Iran. Patients and Methods: Between 1997 and 2008, 102 patients were enrolled in the study. Patients were diagnosed using the International Autoimmune Hepatitis Group criteria and were followed up for an average of 60 months. Clinical and biochemical data were gathered from all the patients at both the beginning and the end of the follow-up period. Liver biopsy was performed in all patients before treatment, and the biopsies were performed in 28 patients after treatment. Results: Biochemical remission was achieved by 80 (79.4%) patients. Of these, 53 (66.5%) showed near-normal liver histology or liver function test results and sonogram. The remaining 27 (33.5%) patients also achieved clinical and biochemical remission, but developed compensated cirrhosis. After a period of remission, 24 patients (32.5%) relapsed. Among the 22 (21.6%) patients who showed ultimate treatment failure, 6 underwent orthotopic liver transplantation and 3 died of liver failure while awaiting a transplant. Sixteen (72.7%) of the 22 patients who did not respond to therapy were non-compliant with medications and had irregular follow-up. The overall 10-year survival rate in the cohort was 96%. Conclusions: Long-term survival in AIH patients is very good. Prompt diagnosis and appropriate first-line and salvage therapy that includes close follow-up will make liver transplantation a rare necessity in the treatment of this disease.

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Section: Discussionmentioning

confidence: 99%

Clinical Features and Long Term Outcome of 102 Treated Autoimmune Hepatitis Patients

et al. 2012

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“…A recent study indicates that quality of life (in particular, the mental well-being) is not normal in patients treated for AIH [7] . Five to fifteen per cent of patients do not respond to treatment and even in those who do, disease relapse occurs in almost 20% of patients despite ongoing treatment [8] and in 45-70% if treatment is stopped [9][10][11] . Most patients with AIH have some degree of liver fibrosis and about 30% have cirrhosis at presentation [12][13][14] .…”

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confidence: 99%

Standard Treatment in Adults: Which Steroid? Or without Steroids?

Gleeson¹

2015

Dig Dis

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Key Messages: (1) Standard treatment of autoimmune hepatitis in adults should be steroid based. In early trials, prednisolone +/- azathioprine was superior to the azathioprine mono-therapy (which was not significantly better than placebo). Prednisolone plus azathioprine has similar efficacy to, but is better tolerated than a higher-dose of prednisolone alone and therefore has become standard therapy. (2) In most treated patients, serum transaminases and globulin/IgG fall, but percentage attaining normal values within 6 months varies between 10 and 90%. Patients failing to do so have a worse longer-term outcome. (3) A higher initial prednisolone dose (1 mg/kg/day) plus azathioprine achieved 76% serum transaminase normalisation after 6 months but needs longer-term evaluation. (4) Histological remission (minimal hepatitis on re-biopsy) lags behind transaminase normalisation by 6-12 months and is achieved in 55-70% of patients after 24-36 months prednisolone. This lag and the inefficacy of azathioprine mono-therapy justifies continuing prednisolone (5-10 mg/day), even after transaminase normalisation, for a total of >2 years. (5) Repeat biopsy should be considered because 40-60% of patients still have (usually mild) persisting inflammation, despite normal serum transaminases and IgG. In such patients, fibrosis is less likely to regress and long-term mortality is higher. (6) In a large trial, non-cirrhotic treatment-naïve patients given budesonide (9 mg/day) plus azathioprine were more likely to achieve normal serum ALT after 6 months than those receiving prednisolone plus azathioprine and had less side effects. This trial was short term in nature and lacked follow-up histology. Budesonide is recommended in non-cirrhotic patients who develop prednisolone-related side effects. In an open study of mycophenolate plus prednisolone, 88% of treatment-naïve patients achieved normal serum transaminases. However, half relapsed during or after steroid withdrawal and only one of eight re-biopsied patients achieved histological remission. Mycophenolate is teratogenic, limiting its use in younger women. Conclusion: Despite its limitations, no regime has yet been shown clearly to be better than prednisolone and azathioprine-based therapy.

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“…The follow-up period was appropriate, since more than 80% of relapses of AIH occur within 12 months of treatment withdrawal (8,10,17,19) . All relapses that occurred in the control group happened within 14 months, whereas 38.8% of the relapses in Group A occurred after this period (including follow-up).…”

Section: Discussionmentioning

confidence: 99%

“…Relapse probability, however, reaches 50% in 6 months and 70% after 1 year, and sustained remission rates go down to between 10%-15% in 5 years (8,22) . Fatal relapses were also described, but are fortunately rare (17) . This unfavorable prognosis is worsened by the increase in corticosteroid-related sideeffects after repeated treatment using higher doses of corticosteroids (37) .…”

Section: Introductionmentioning

confidence: 99%

Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study

Mucenic

Mello

Cançado

2005

Arq. Gastroenterol.

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-Background -Due to the risks related to long-term treatment with prednisone and azathioprine, most clinicians try to withdraw these drugs when patients with autoimmune hepatitis are in remission. However, there is a high probability of relapse, and most patients end up receiving maintenance treatment. Aim -To evaluate the safety and efficacy of maintenance treatment with chloroquine in the prevention of autoimmune hepatitis relapses. Methods -Classical treatment was stopped after achievement of biochemical and histological remission of autoimmune hepatitis. Chloroquine diphosphate, 250 mg daily, was given for at least 12 months or until the occurrence of relapses defined by levels of aminotransferases at least twice the upper normal values. Results -Fourteen patients were consecutively treated and compared with 18 historical controls. There was a 6.49 (1.38-30.30) greater chance of relapse in the historical controls when compared with patients treated with chloroquine (72.2% x 23.5%; 0.031). Conclusions -The group treated with chloroquine had a lower frequency of relapses. Chloroquine was safe in patients with autoimmune hepatitis and hepatic cirrhosis without decompensation, on 250 mg daily up to 2 years. These preliminary results provide a basis for upcoming controlled studies comparing chloroquine with placebo or for maintenance treatment with prednisone and/or azathioprine for the prevention of autoimmune hepatitis relapses.

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Relapse Following Treatment Withdrawal in Patients with Autoimmune Chronic Active Hepatitis

Cited by 164 publications

References 12 publications

Clinical Features and Long Term Outcome of 102 Treated Autoimmune Hepatitis Patients

Clinical Features and Long Term Outcome of 102 Treated Autoimmune Hepatitis Patients

Standard Treatment in Adults: Which Steroid? Or without Steroids?

Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study

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