Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs
- This uncommissioned systematic review was subject to full peer-review.
Dr A. J. Montano-Loza, Zeidler Ledcor Centre, 130 University Campus, University of Alberta, Edmonton, AB T6G 2X8, Canada.
Corticosteroid treatment for autoimmune hepatitis has been shown by randomised controlled clinical trials to ameliorate symptoms, normalise liver tests, improve histological findings and extend survival. Nevertheless, suboptimal responses to corticosteroid treatment still occur.
To describe the current definitions, frequencies, clinical relevance and treatment options for suboptimal responses, and to discuss alternative medications that have been used off-label for these occurrences.
Literature search was made for full-text papers published in English using the keyword ‘autoimmune hepatitis’. Authors' personal experience and investigational studies also helped to identify important contributions to the literature.
Suboptimal responses to standard therapy include treatment failure (7%), incomplete response (14%), drug toxicity (13%) and relapse after drug withdrawal (50–86%). The probability of a suboptimal response prior to treatment is higher in young patients and in patients with a severe presentation, jaundice, high MELD score at diagnosis, multilobular necrosis or cirrhosis, antibodies to soluble liver antigen, or inability to improve by clinical indices within two weeks or by MELD score within 7 days of conventional corticosteroid treatment. Management strategies have been developed for the adverse responses and nonstandard drugs, including mycophenolate mofetil, budesonide, ciclosporin, tacrolimus, sirolimus and rituximab, are emerging as rescue therapies or alternative frontline agents.
Once diagnosed, the suboptimal response should be treated by a highly individualised and well-monitored regimen, preferentially using first-line therapy. Nonstandard drugs warrant consideration as salvage or second-line therapies.