Matsumoto Kosuke, Hirohara Junko, Takeuchi Akihito, Miura Ryo, Asaoka Yoshinari, Nakano Toshiaki, Tanaka Atsushi
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Hepatol Res. 2023 Oct;53(10):989-997. doi: 10.1111/hepr.13931. Epub 2023 Jun 21.
For patients with primary biliary cholangitis (PBC) exhibiting suboptimal responses to ursodeoxycholic acid (UDCA), obeticholic acid (OCA), and bezafibrate (BZF) are currently used and shown to improve long-term outcomes. Nevertheless, we encounter patients who die or undergo liver transplantation (LT) even with combination treatment. In this study, we explored prognostic indicators in patients receiving combination treatment of UDCA and BZF.
We took advantage of the Japanese PBC registry and enrolled patients who received both UDCA and BZF therapy in 2000 or later. The covariates investigated included baseline covariates as well as treatment covariates. Two main outcomes (all-cause death or LT and liver-related death or LT) were assessed using multivariable-adjusted Cox proportional hazards models.
In total, 772 patients were included. The median follow-up was 7.1 years. Using the Cox regression model, bilirubin (hazard ratio [HR] 6.85, 95% confidence interval [CI] 1.73-27.1, p = 0.006), alkaline phosphatase (HR 5.46, 95% CI 1.32-22.6, p = 0.019), and histological stage (HR 4.87, 95% CI 1.16-20.5, p = 0.031) were found associated with LT-free survival. For survival free from liver disease-related death or LT, albumin (HR 7.72, 95% CI 1.48-40.4, p = 0.016) and bilirubin (HR 14.5, 95% CI 2.37-88.5, p = 0.004) were found significantly associated.
In patients with PBC receiving combination therapy, prognostic variables were similar to those in patients receiving UDCA monotherapy. These results indicate the importance of diagnosing patients with PBC at an earlier stage because of the reduced effectiveness of BZF at advanced stages.
对于原发性胆汁性胆管炎（PBC）患者，若对熊去氧胆酸（UDCA）反应欠佳，目前会使用奥贝胆酸（OCA）和苯扎贝特（BZF），且已证明它们可改善长期预后。然而，即便采用联合治疗，我们仍会遇到患者死亡或接受肝移植（LT）的情况。在本研究中，我们探索了接受UDCA和BZF联合治疗患者的预后指标。
我们利用日本PBC登记系统，纳入了2000年及以后接受UDCA和BZF治疗的患者。所调查的协变量包括基线协变量以及治疗协变量。使用多变量调整的Cox比例风险模型评估两个主要结局（全因死亡或LT以及肝病相关死亡或LT）。
共纳入772例患者。中位随访时间为7.1年。使用Cox回归模型，发现胆红素（风险比[HR] 6.85，95%置信区间[CI] 1.73 - 27.1，p = 0.006）、碱性磷酸酶（HR 5.46，95% CI 1.32 - 22.6，p = 0.019）和组织学分期（HR 4.87，95% CI 1.16 - 20.5，p = 0.031）与无LT生存相关。对于无肝病相关死亡或LT的生存情况，发现白蛋白（HR 7.72，95% CI 1.48 - 40.4，p = 0.016）和胆红素（HR 14.5，95% CI 2.37 - 88.5，p = 0.004）显著相关。
在接受联合治疗的PBC患者中，预后变量与接受UDCA单药治疗的患者相似。这些结果表明，由于BZF在疾病晚期效果降低，早期诊断PBC患者很重要。
