RESUMEN
BACKGROUND: In patients with primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA), the presence of moderate-to-severe interface hepatitis is associated with a higher risk of liver transplantation and death. This highlights the need for novel treatment approaches. In this study, we aimed to investigate whether combination therapy of UDCA and immunosuppressant (IS) was more effective than UDCA monotherapy. METHODS: We conducted a multicenter study involving PBC patients with moderate-to-severe interface hepatitis who underwent paired liver biopsies. Firstly, we compared the efficacy of the combination therapy with UDCA monotherapy on improving biochemistry, histology, survival rates, and prognosis. Subsequently we investigated the predictors of a beneficial response. RESULTS: This retrospective cohort study with prospectively collected data was conducted in China from January 2009 to April 2023. Of the 198 enrolled patients, 32 underwent UDCA monotherapy, while 166 received combination therapy, consisting of UDCA combined with prednisolone, prednisolone plus mycophenolate mofetil (MMF), or prednisolone plus azathioprine (AZA). The monotherapy group was treated for a median duration of 37.6 months (IQR 27.5-58.1), and the combination therapy group had a median treatment duration of 39.3 months (IQR 34.5-48.8). The combination therapy showed a significantly greater efficacy in reducing fibrosis compared to UDCA monotherapy, with an 8.3-fold increase in the regression rate (from 6.3% to 52.4%, P < 0.001). Other parameters, including biochemistry, survival rates, and prognosis, supported its effectiveness. Baseline IgG >1.3 × ULN and ALP <2.4 × ULN were identified as predictors of regression following the combination therapy. A predictive score named FRS, combining these variables, accurately identified individuals achieving fibrosis regression with a cut-off point of ≥ -0.163. The predictive value was validated internally and externally. CONCLUSION: Combination therapy with IS improves outcomes in PBC patients with moderate-to-severe interface hepatitis compared to UDCA monotherapy. Baseline IgG and ALP are the most significant predictors of fibrosis regression. The new predictive score, FRS, incorporating baseline IgG and ALP, can effectively identify individuals who would benefit from the combination therapy.