Yen Fu-Shun, Wei James Cheng-Chung, Chiu Lu-Ting, Hsu Chih-Cheng, Hou Ming-Chih, Hwu Chii-Min
Dr. Yen's Clinic, Taoyuan City, Taiwan.
Division of Allergy, Immunology and Rheumatology Chung, Shan Medical University Hospital, Taichung, Taiwan.
Liver Int. 2021 Jan;41(1):110-122. doi: 10.1111/liv.14714. Epub 2020 Nov 11.
BACKGROUND& AIMS: Type 2 diabetes mellitus (T2DM) management in patients with cirrhosis is complicated. No clinical trials have investigated appropriate antidiabetic drug use in these patients. This study compared the risks of all-cause mortality, major adverse cardiovascular events (MACE) and hepatic outcomes between patients with T2DM and cirrhosis using and not using thiazolidinedione (TZD).
We selected 1,705 propensity score-matched TZD users and nonusers from a Taiwan National Health Insurance Research Database cohort of T2DM patients with compensated cirrhosis between January 1, 2000, and December 31, 2012 and followed them until December 31, 2013. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risks of investigated outcomes for TZD users.
MACE incidence rates during follow-up were 2.14 and 1.30 per 100 patient-years for TZD users and nonusers, respectively (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI], 1.32-2.19). On the basis of TZD use, the aHRs (95% CIs) for stroke, ischemic heart disease and heart failure were 1.81 (1.28-2.55), 1.59 (1.03-2.44) and 2.09 (1.22-3.60) respectively. Compared with TZD nonusers, rosiglitazone users had significantly higher aHR [1.67 (1.26-2.20)] and pioglitazone users had no significant difference of aHR [1.12 (0.90-1.64)]. All-cause mortality, hepatocellular carcinoma, decompensated cirrhosis and hepatic failure risks did not differ significantly between TZD users and nonusers.
Compared with nonuser, TZD users demonstrated significantly higher MACE risks. Therefore, the risks of cardiovascular complications should be considered when prescribing TZDs to patients with T2DM and cirrhosis.
肝硬化患者的2型糖尿病（T2DM）管理较为复杂。尚无临床试验研究这些患者使用何种抗糖尿病药物合适。本研究比较了使用和未使用噻唑烷二酮（TZD）的T2DM合并肝硬化患者的全因死亡率、主要不良心血管事件（MACE）风险和肝脏转归。
我们从台湾国民健康保险研究数据库中，选取了2000年1月1日至2012年12月31日期间代偿期肝硬化的T2DM患者队列中的1705名倾向评分匹配的TZD使用者和非使用者，并随访至2013年12月31日。采用具有稳健三明治标准误估计的Cox比例风险模型评估TZD使用者的研究转归风险。
随访期间，TZD使用者和非使用者的MACE发病率分别为每100患者年2.14例和1.30例（调整后风险比[aHR]1.70；95%置信区间[CI]，1.32 - 2.19）。基于TZD的使用情况，中风、缺血性心脏病和心力衰竭的aHR（95%CI）分别为1.81（1.28 - 2.55）、1.59（1.03 - 2.44）和2.09（1.22 - 3.60）。与未使用TZD者相比，罗格列酮使用者的aHR显著更高[1.67（1.26 - 2.20）]，而吡格列酮使用者的aHR无显著差异[1.12（0.90 - 1.64）]。TZD使用者和非使用者之间的全因死亡率、肝细胞癌、失代偿期肝硬化和肝衰竭风险无显著差异。
与未使用者相比，TZD使用者的MACE风险显著更高。因此，在为T2DM合并肝硬化患者处方TZD时，应考虑心血管并发症的风险。
