Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
Am J Gastroenterol. 2018 Jan;113(1):49-55. doi: 10.1038/ajg.2017.287. Epub 2017 Oct 10.
Adding fibrates improves liver biochemistries in patients with primary biliary cholangitis (PBC) and suboptimal response to ursodeoxycholic acid (UDCA). As there are no consistent data regarding the course and outcome, we have assessed the effects of the combined treatment with UDCA and bezafibrate on a long-term basis.
A total of 48 patients (45 female) with PBC treated with UDCA and alkaline phosphatase (ALP) above 1.5 times upper normal levels (× UNL) were treated with bezafibrate (400 mg/day) plus UDCA (13-16 mg/kg/day). Changes in clinical features, liver biochemistries, and prognosis after therapy were assessed, as well as pruritus, using a visual analog scale (43 patients) and the 5-D descriptive pruritus scale.
After a median of 38 months, 26 patients (54%) had normalized ALP. In these patients, jaundice, pruritus, and liver stiffness was lower, and age was higher than in patients who remained with elevated ALP. Biochemical improvement was less prominent in patients without ALP normalization. Five of these patients (23%) developed events of disease progression: 1 died, 3 were transplanted, and 1 developed hepatocellular carcinoma. Partial or complete itching relief was reported in all but one case with pruritus. Itching recurrence or worsening was observed after bezafibrate discontinuation.
The long-term treatment with UDCA and bezafibrate results in excellent response, and is associated with a complete or partial itching relief. Incomplete ALP normalization was observed in patients with advanced disease who remained at risk for developing severe events. The combined treatment is mainly effective in patients with lower fibrosis and severity of cholestasis.
在原发性胆汁性胆管炎(PBC)患者中,添加贝特类药物可改善肝生化指标,但对熊去氧胆酸(UDCA)反应不佳。由于目前尚无关于该疾病病程和结局的一致性数据,我们评估了长期联合应用 UDCA 和苯扎贝特治疗的效果。
共有 48 例(45 例女性)接受 UDCA 治疗且碱性磷酸酶(ALP)高于正常值上限 1.5 倍(×UNL)的 PBC 患者接受苯扎贝特(400mg/天)联合 UDCA(13-16mg/kg/天)治疗。评估治疗后临床特征、肝生化指标和预后的变化,以及瘙痒情况(43 例患者采用视觉模拟量表,5 项描述性瘙痒量表)。
中位数为 38 个月后,26 例(54%)患者 ALP 恢复正常。在这些患者中,黄疸、瘙痒和肝硬度降低,年龄高于 ALP 持续升高的患者。未达到 ALP 正常化的患者生化改善不明显。这些患者中有 5 例(23%)发生疾病进展事件:1 例死亡,3 例接受肝移植,1 例发生肝细胞癌。所有有瘙痒症状的患者(除 1 例外)均报告瘙痒缓解,部分或完全缓解。停止使用苯扎贝特后,瘙痒复发或加重。
长期应用 UDCA 和苯扎贝特治疗可获得良好的疗效,与完全或部分瘙痒缓解相关。在疾病进展风险较高的晚期患者中,观察到 ALP 不完全正常。联合治疗主要对纤维化和胆汁淤积程度较低的患者有效。