Treatment options for autoimmune hepatitis: A systematic review of randomized controlled trials

Lamers, Mieke M.H.; van Oijen, Martijn G.H.; Pronk, Martine; Drenth, Joost P.H.

doi:10.1016/j.jhep.2010.01.037

« Previous Next »Journal of Hepatology
Volume 53, Issue 1 , Pages 191-198, July 2010

Treatment options for autoimmune hepatitis: A systematic review of randomized controlled trials

Mieke M.H. Lamers
- Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Martijn G.H. van Oijen
- Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Martine Pronk
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
Joost P.H. Drenth
- Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
- Corresponding author. Address: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, code 455, 6500 HB Nijmegen, The Netherlands. Tel.: +31 24 3614760; fax: +31 24 3540103.

published online 30 March 2010.

Background & Aims

Predniso(lo)ne with or without azathioprine is considered the mainstay in the treatment of autoimmune hepatitis (AIH), but many therapeutic options are available. The primary objective of this review was to explore the published literature on the optimal induction and subsequent maintenance therapy for AIH.

Methods

We performed a systematic search on electronic databases MEDLINE (1950-07.2009), Web of Science, Cochrane, and the website www.clinicaltrials.gov. Randomized controlled trials (RCTs) on apparent beneficial treatment regimens as induction or maintenance treatment in AIH were included. Pediatric studies were excluded. We calculated relative risks (RR) for comparison of treatment options on the primary outcome measure, which was defined as clinical, biochemical and histological remission.

Results

Eleven RCTs were included, of which 7 studies evaluated the induction therapy in AIH patients: 3 treatment naive (n=253), 2 relapse (n=53), 2 combination of naive and relapse (n=110). The remaining 4 studies (n=162) assessed maintenance therapy. All but one maintenance study (thymostimulin versus no therapy) studied predniso(lo)ne (PRED), azathioprine (AZA) or combination PRED+AZA. We found no differences in primary outcome between induction therapy with PRED and PRED+AZA in treatment naive patients (RR=0.98; 95% CI 0.65–1.47). AZA monotherapy as induction was considered as not viable because of a high mortality rate (30%). This was similar in AIH patients who relapsed: RR for PRED versus PRED+AZA for inducing remission was not different: 0.71 (95% CI 0.37–1.39). PRED+AZA maintained remission more often than PRED (RR=1.40; 95% CI 1.13–1.73). Also AZA maintained a higher remission rate than PRED (RR=1.35; 95% CI 1.07–1.70). Maintenance of remission was not different between PRED+AZA and AZA (RR=1.06; 95% CI 0.94–1.20).

Conclusions

Based on available RCTs, PRED monotherapy and PRED+AZA combination therapy are both viable induction therapies for AIH treatment naives and relapsers, while for maintenance therapy PRED+AZA and AZA therapy are superior to PRED monotherapy.

Abbreviations: AIH, autoimmune hepatitis, PRED, predniso(lo)ne, AZA, azathioprine, PRED+AZA, predniso(lo)ne+azathioprine, RCTs, randomized controlled trials