Published online Oct 14, 2020. doi: 10.3748/wjg.v26.i38.5896
Peer-review started: May 28, 2020
First decision: August 9, 2020
Revised: August 11, 2020
Accepted: September 17, 2020
Article in press: September 17, 2020
Published online: October 14, 2020
The standard treatment of autoimmune hepatitis (AIH) is based on corticosteroids, either given alone or in combination with azathioprine, which both lead to remission in 80% of patients. Second-line treatments are needed for patients who have refractory disease. Tacrolimus and mycophenolate mofetil (MMF) have empirically been used the most, as second line treatments for AIH. However, high-quality data on the alternative management of AIH are scarce.
The accumulating but still sparse data indicate that refractory AIH patients do respond to these second-line treatments. However, there is no firm evidence of their effectiveness.
The aims of this study were to evaluate the efficacy and safety of tacrolimus and MMF and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).
A systematic review and meta-analysis of the available data were performed. We reviewed the literature, focusing on our aim to identify, appraise, select and synthesize all the high-quality evidence available. We calculated pooled event rates for three outcome measures, defined as biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals. Random effects model was applied whenever there was significant heterogeneity between studies. The GRADE approach was used to assess the quality of evidence for primary and secondary outcomes.
Overall, 21 observational studies, comprising 584 patients with AIH who were unable to tolerate or respond to first-line treatment, met our eligibility criteria. Tacrolimus is efficient in treating patients who did not respond to first-line treatments, yielding a biochemical remission rate of 59.1%, while MMF is considered effective for patients who are intolerant to the first-line therapy, yielding a biochemical remission rate of 73.5%. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.
The available evidence shows tacrolimus and MMF are in practice considered effective for AIH patients who are non-responder or intolerant to first-line treatment, but we found no high-quality evidence to support this statement and the translation of these findings to AIH clinical guidelines is questionable.
Well-planned, prospective, multicenter studies of second-line treatments for patients with AIH would help to define the optimal dose, treatment schedule, required duration, and treatment endpoints. In addition, such studies should perform close monitoring of the side-effects.