Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
J Hepatol. 2021 Sep;75(3):565-571. doi: 10.1016/j.jhep.2021.04.010. Epub 2021 Apr 18.
BACKGROUND & AIMS: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort.
All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT).
Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p <0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively.
In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis.
The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all-cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes.
已有报道称，对于熊去氧胆酸（UDCA）应答不完全的原发性胆汁性胆管炎（PBC）患者，苯扎贝特（BZF）可改善症状和生化特征，但长期生存影响仍不清楚。在日本，自 2000 年以来，BZF 一直被用作 PBC 的事实上的二线治疗药物。在此，我们比较了在一个大型日本 PBC 队列中接受和未接受 BZF 治疗的患者的生存率。
本队列所有连续注册的患者，自 2000 年起开始接受 UDCA 治疗且随访时间≥1 年，纳入本研究。采用时间依赖性、多变量和倾向评分调整 Cox 比例风险模型评估 BZF 暴露与死亡率或肝移植（LT）需求之间的关系。使用需要治疗的人数（NNT）来量化临床获益。
在 3908 例符合条件的患者中，3162 例（81%）仅接受 UDCA 治疗，746 例（19%）接受 UDCA 和 BZF 治疗，分别随访了 17360 和 3932 患者年。随访期间，登记了 183 例死亡（89 例与肝脏相关）和 21 例 LT。联合治疗组全因死亡率和肝脏相关死亡率或 LT 需求显著降低（调整后的风险比分别为 0.3253（95%CI，0.1936-0.5466）和 0.2748（95%CI，0.1336-0.5655）；均<0.001）。这种关联在基线时的各种风险组中均一致。联合治疗组预防 5、10 和 15 年时额外 1 例死亡或 LT 发生的 NNT 分别为 29（95%CI，22-46）、14（10-22）和 8（6-15）。
在 PBC 患者治疗效果的大型回顾性队列研究中，BZF 联合 UDCA 治疗与改善预后相关。
对于 UDCA 应答不完全的 PBC 患者，苯扎贝特（BZF）在肝移植（LT）无复发生存方面的长期疗效仍有待确定。在这项日本全国性回顾性队列研究中，与单独使用 UDCA 相比，使用 UDCA-BZF 联合治疗与较低的全因死亡率和肝脏相关死亡率或 LT 需求风险相关。这些结果表明，BZF 是迄今为止唯一在改善症状、生化标志物和长期结局方面显示出疗效的 PBC 药物。
