Tsuji Keiji, Tamaki Nobuharu, Kurosaki Masayuki, Mori Nami, Takaki Shintaro, Ohya Kazuki, Mashiba Toshie, Ochi Hironori, Kobashi Haruhiko, Ogawa Chikara, Nonogi Michiko, Yoshida Hideo, Akahane Takehiro, Kondo Masahiko, Kasai Toyotaka, Fujii Hideki, Uchida Yasushi, Arai Hirotaka, Tsuchiya Kaoru, Izumi Namiki
Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Hepatol Res. 2025 May;55(5):675-684. doi: 10.1111/hepr.14172. Epub 2025 Feb 19.
We aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, on patients with primary biliary cholangitis (PBC) complicated by dyslipidemia.
In total, 61 patients with PBC (Add-on group: 33 patients on ursodeoxycholic acid [UDCA] + pemafibrate combination therapy; Switch group: 28 patients who switched from UDCA + other fibrates to UDCA + pemafibrate combination therapy) were included in the study. Changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and GLOBE scores were retrospectively analyzed from 6 months before to 12 months after treatment. The POISE criteria were also used to evaluate the treatment efficacy after 12 months.
After 12 months of UDCA + pemafibrate combination therapy, AST significantly decreased from 45 ± 3 to 28 ± 3 U/L (p < 0.05), ALT from 49 ± 5 to 32 ± 5 U/L (p < 0.005), GGT from 155 ± 223 to 91 ± 182 U/L (p < 0.005), and ALP from 1.4 ± 0.9 to 0.9 ± 0.8 × upper limit of normal (p < 0.0005) in all patients. ALT, GGT, and ALP levels were significantly lower after 12 months of UDCA + pemafibrate combination therapy in both the Add-on and Switch groups. After 12 months of combination therapy, the mean GLOBE score of all patients significantly decreased from 0.37 to 0.01 (p < 0.05) and the percentage of patients with a GLOBE score of 0.3 or higher decreased.
In patients with PBC who showed an inadequate response to prior therapy, pemafibrate add-on or switch therapy improved liver biochemistry and GLOBE scores. Pemafibrate may be useful as a second-line drug when UDCA alone is inadequate, or as an alternative after combination therapy with other fibrates.
我们旨在评估选择性过氧化物酶体增殖物激活受体-α调节剂匹伐他汀对原发性胆汁性胆管炎（PBC）合并血脂异常患者的疗效。
本研究共纳入61例PBC患者（联合治疗组：33例患者接受熊去氧胆酸[UDCA] + 匹伐他汀联合治疗；换药组：28例患者从UDCA + 其他贝特类药物转换为UDCA + 匹伐他汀联合治疗）。回顾性分析治疗前6个月至治疗后12个月天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、γ-谷氨酰转移酶（GGT）、碱性磷酸酶（ALP）及GLOBE评分的变化。12个月后还采用POISE标准评估治疗效果。
UDCA + 匹伐他汀联合治疗12个月后，所有患者的AST从45±3显著降至28±3 U/L（p < 0.05），ALT从49±5降至32±5 U/L（p < 0.005），GGT从155±223降至91±182 U/L（p < 0.005），ALP从1.4±0.9降至0.9±0.8×正常上限（p < 0.0005）。在联合治疗组和换药组中UDCA + 匹伐他汀联合治疗12个月后ALT、GGT和ALP水平均显著降低。联合治疗12个月后，所有患者的平均GLOBE评分从0.37显著降至0.01（p < 0.05），GLOBE评分≥0.3的患者百分比降低。
在对先前治疗反应不佳的PBC患者中，添加匹伐他汀或换药治疗可改善肝脏生化指标和GLOBE评分。当单独使用UDCA疗效不佳时，匹伐他汀可作为二线药物，或在与其他贝特类药物联合治疗后作为替代药物。
