Original article
Pancreas, biliary tract, and liver
Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy

https://doi.org/10.1016/j.cgh.2017.09.063Get rights and content

Background & Aims

Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine.

Methods

We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment.

Results

The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events.

Conclusion

In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

Section snippets

Study Design

This was a multicenter, retrospective study of cases of AIH managed across 17 metropolitan and regional liver centers affiliated with the ALA CRN. Medical records of AIH subjects who fulfilled eligibility criteria were identified from multiple hospital resources including pharmacy prescription databases, health information services, electronic medical records, and existing liver clinic databases. Data recorded in the patients’ medical records during clinic visits were transcribed onto a

Study Population

One hundred nine patients with an established diagnosis of AIH and treatment with MMF were identified. Of these, 4 were excluded for the efficacy analysis because of follow-up <1 month (n = 3) and concomitant hepatitis C infection (n = 1), leaving a final cohort of 105 patients. The baseline characteristics of this cohort are shown in Table 1. As expected, the cohort predominantly involved white women, with the vast majority (97%) having type 1 AIH and the mean age being 50 years at diagnosis

Discussion

To our knowledge this is the largest study evaluating the efficacy and safety of MMF as rescue therapy in adult patients with AIH who are refractory and/or intolerant to therapy with corticosteroids with or without thiopurine(s). Using the resources of the ALA CRN, we identified 105 patients across 17 sites who met protocol-specified criteria for study inclusion, of whom around 40% had cirrhosis. The main findings of the study were that treatment with MMF appeared well-tolerated in patients and

References (35)

  • K. Zachou et al.

    Mycophenolate for the treatment of autoimmune hepatitis: prospective assessment of its efficacy and safety for induction and maintenance of remission in a large cohort of treatment-naïve patients

    J Hepatol

    (2011)
  • E.L. Krawitt

    Autoimmune hepatitis

    N Engl J Med

    (2006)
  • M. Werner et al.

    Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study

    Scand J Gastroenterol

    (2008)
  • A.J. Czaja et al.

    Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis

    Gastroenterology

    (2010)
  • J.S. Delgado et al.

    Autoimmune hepatitis in southern Israel: a 15-year multicentre study

    J Dig Dis

    (2013)
  • M.P. Manns et al.

    Diagnosis and management of autoimmune hepatitis

    Hepatology

    (2010)
  • V. Selvarajah et al.

    Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs

    Aliment Pharmacol Ther

    (2012)
  • Cited by (0)

    Conflicts of interest The authors disclose no conflicts.

    View full text