Department of Rheumatology, Military Hospital, 1008, Tunis, Tunisia.
University of Tunis El Manar, 1068, Tunis, Tunisia.
Clin Rheumatol. 2024 Mar;43(3):929-938. doi: 10.1007/s10067-023-06847-7. Epub 2023 Dec 30.
There are conflicting findings on the link between liver fibrosis and cumulative methotrexate dosages. We aimed to determine the frequency of liver fibrosis in rheumatoid arthritis patients treated with methotrexate and to identify its associated factors.
We conducted a cross-sectional study over 9 months (April-December 2021), including rheumatoid arthritis patients treated with methotrexate. Demographic and clinical data were collected. Liver stiffness was assessed by FibroScan. Fibrosis and significant liver fibrosis were defined as liver stiffness higher than 6 and 7.2 kPa, respectively. Liver tests, albuminemia, lipid profile, and blood glycemia were measured. Metabolic syndrome was also evaluated. Statistical analyses were performed using SPSS.
We included 21 men and 47 women. The mean age was 51.60 ± 1.82 years. The mean disease duration was 8.29 ± 6.48 years. The mean weekly intake of methotrexate was 13.76 ± 3.91 mg. The mean methotrexate duration was 4.67 ± 4.24 years. The mean cumulative dose was 3508.87 ± 3390.48 mg. Hypoalbuminemia and metabolic syndrome were found in 34% and 25% of cases. We noted increased alkaline phosphatase levels in four cases. The mean liver stiffness was 4.50 ± 1.53 kPa. Nine patients had liver fibrosis, and four had significant fibrosis. Associated factors with liver fibrosis were as follows: age ≥ 60 years (OR:22.703; CI [1.238-416.487]; p = 0.035), cumulated dose of methotrexate ≥ 3 g (OR: 76.501; CI [2.383-2456.070]; p = 0.014), metabolic syndrome (OR: 42.743; CI [1.728-1057.273]; p = 0.022), elevated alkaline phosphatase levels (OR: 28.252; CI [1.306-611.007]; p = 0.033), and hypoalbuminemia (OR: 59.302; CI [2.361-1489.718]; p = 0.013).
Cumulating more than 3 g of methotrexate was associated with liver fibrosis in rheumatoid arthritis patients. Having a metabolic syndrome, higher age, hypoalbuminemia, and elevated alkaline phosphatase levels were also likely to be independently associated with liver fibrosis. Key points • Rheumatoid arthritis patients require monitoring hepatic fibrosis when the cumulated dose of methotrexate is above 3 g. • Metabolic syndrome is a risk factor for liver fibrosis, suggesting that its management is necessary to prevent this complication. • Hypoalbuminemia and elevated alkaline phosphatase levels (twice the upper limit) in rheumatoid arthritis patients treated with methotrexate were associated with liver fibrosis.
肝纤维化与累积甲氨蝶呤剂量之间的关系存在争议。我们旨在确定接受甲氨蝶呤治疗的类风湿关节炎患者肝纤维化的频率，并确定其相关因素。
我们进行了一项为期 9 个月的横断面研究（2021 年 4 月至 12 月），包括接受甲氨蝶呤治疗的类风湿关节炎患者。收集了人口统计学和临床数据。通过 FibroScan 评估肝硬度。纤维化和显著肝纤维化定义为肝硬度高于 6 和 7.2 kPa。测量了肝功能、白蛋白血症、血脂谱和血糖。还评估了代谢综合征。使用 SPSS 进行了统计分析。
我们纳入了 21 名男性和 47 名女性。平均年龄为 51.60 ± 1.82 岁。平均病程为 8.29 ± 6.48 年。平均每周甲氨蝶呤摄入量为 13.76 ± 3.91 mg。甲氨蝶呤的平均持续时间为 4.67 ± 4.24 年。累积剂量为 3508.87 ± 3390.48 mg。34%和 25%的病例出现低白蛋白血症和代谢综合征。我们注意到有 4 例碱性磷酸酶水平升高。平均肝硬度为 4.50 ± 1.53 kPa。9 名患者有肝纤维化，4 名患者有显著纤维化。与肝纤维化相关的因素如下：年龄≥60 岁（OR：22.703；CI [1.238-416.487]；p = 0.035）、累积甲氨蝶呤剂量≥3 g（OR：76.501；CI [2.383-2456.070]；p = 0.014）、代谢综合征（OR：42.743；CI [1.728-1057.273]；p = 0.022）、碱性磷酸酶水平升高（OR：28.252；CI [1.306-611.007]；p = 0.033）和低白蛋白血症（OR：59.302；CI [2.361-1489.718]；p = 0.013）。
累积超过 3 g 的甲氨蝶呤与类风湿关节炎患者的肝纤维化有关。代谢综合征、年龄较大、低白蛋白血症和碱性磷酸酶水平升高也可能与肝纤维化独立相关。关键点• 当累积甲氨蝶呤剂量超过 3 g 时，类风湿关节炎患者需要监测肝纤维化。• 代谢综合征是肝纤维化的一个危险因素，这表明需要对其进行管理，以预防这种并发症。• 接受甲氨蝶呤治疗的类风湿关节炎患者出现低白蛋白血症和碱性磷酸酶水平升高（两倍上限）与肝纤维化相关。
