Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis

Background & Aims: For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. Methods: We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n= 30) or a combination of UDCA and immunosuppression (n= 58). Results: Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P= .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P= .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). Conclusions: In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.