Department of Gastroenterology and Hepatology, University Hospital "José de San Martín", Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Biotechnology Institute of Misiones (INBIOMIS), National University of Misiones, National Scientific and Technical Research Council (CONICET), Posadas, Argentina.
Aliment Pharmacol Ther. 2021 Nov;54(9):1202-1212. doi: 10.1111/apt.16618. Epub 2021 Sep 29.
Ursodeoxycholic acid (UDCA) is the first-line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients.
To evaluate the long-term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA-refractory PBC.
Fifty-nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow-up.
Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA-bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P < 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK-PBC prognosis models.
Adding bezafibrate to UDCA in patients with UDCA-refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long-term cohort studies and controlled trials.
熊去氧胆酸（UDCA）是原发性胆汁性胆管炎（PBC）的一线治疗药物。然而，近 40%的患者对 UDCA 反应不完全。在这组患者中，添加苯扎贝特已显示出生化获益。
评估 UDCA 联合苯扎贝特治疗 UDCA 抵抗性 PBC 患者的长期疗效。
纳入 59 例 UDCA 抵抗的患者。监测临床参数，并在随访 5 年后进行配对肝活检（PLB）。
在总队列中，分析了 49 例患者，其中 31 例在 5 年后进行了 PLB。UDCA-苯扎贝特治疗后，血清碱性磷酸酶（ALP）、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和γ-谷氨酰转移酶（GGT）显著改善。这种有益的效果在 12 个月时就观察到，86%的患者 ALP 水平恢复正常。PLB 分析显示，肝损伤明显减轻，Ludwig 评分（基线 2.29±1.2，5 年时为 1.84±1，P=0.0242）和 Ishak 评分（基线 6.19±2.2，5 年时为 4.77±2.2，P=0.0008）均有显著下降。总体而言，48%的患者纤维化得到缓解。此外，我们观察到肝硬化的比例从基线时的 19%降至 5 年后的 3%（P<0.001）。这些有益的效果与 GLOBE 和 UK-PBC 预后模型的预测风险评分显著降低相关。
在 UDCA 抵抗性 PBC 患者中，加用苯扎贝特可显著降低纤维化和炎症组织学评分，在 5 年后达到显著改善。这些有益的效果需要在长期队列研究和对照试验中进一步评估。
