背景:在接受熊去氧胆酸(UDCA)治疗的原发性胆汁性胆管炎(PBC)患者中,中重度界面性肝炎的存在与较高的肝移植和死亡风险相关.这凸显了对新型治疗方法的需求。在这项研究中,我们旨在研究UDCA和免疫抑制剂(IS)联合治疗是否比UDCA单药治疗更有效.
方法:我们进行了一项多中心研究,涉及接受配对肝活检的中度至重度界面性肝炎PBC患者。首先,我们比较了联合疗法与UDCA单一疗法在改善生物化学方面的疗效,组织学,存活率,和预后。随后,我们研究了有益反应的预测因素。
结果:这项具有前瞻性收集数据的回顾性队列研究于2009年1月至2023年4月在中国进行。在198名登记的患者中,32例接受了UDCA单药治疗,166人接受联合治疗,由UDCA联合泼尼松龙组成,泼尼松龙加霉酚酸酯(MMF),或泼尼松龙加硫唑嘌呤(AZA)。单药治疗组的中位治疗时间为37.6个月(IQR27.5-58.1),联合治疗组的中位治疗持续时间为39.3个月(IQR34.5-48.8).与UDCA单药治疗相比,联合治疗在减少纤维化方面表现出明显更大的疗效。回归率提高了8.3倍(从6.3%提高到52.4%,P<0.001)。其他参数,包括生物化学,存活率,和预后,支持其有效性。基线IgG>1.3×ULN和ALP<2.4×ULN被鉴定为联合治疗后消退的预测因子。一个名为FRS的预测分数,结合这些变量,准确地识别出实现纤维化消退的个体,其临界点≥-0.163。预测值在内部和外部进行了验证。
结论:与UDCA单药治疗相比,IS联合治疗可改善中重度界面性肝炎PBC患者的预后。基线IgG和ALP是纤维化消退的最显著预测因子。新的预测分数,FRS,纳入基线IgG和ALP,可以有效地识别将从联合治疗中受益的个体。
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.
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.
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.
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.