Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Liver Int. 2021 Oct;41(10):2308-2317. doi: 10.1111/liv.14973. Epub 2021 Jun 15.
The effect of major depression and antidepressant use on patient survival in chronic liver disease is unknown. We evaluated the impact of major depressive disorder (MDD) and antidepressants on survival among patients with alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).
The Health Improvement Network database, the largest medical database in the United Kingdom, was used to identify incident ALD (n = 4148) and NAFLD (n = 19 053) in patients between 1986 and 2017. Our primary outcome was development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models as time-varying covariates. Models were adjusted for age, sex, socio-economic status and comorbidities.
MDD rate was higher among patients with ALD (22.8%) compared to those with NAFLD (16.1%), P < .01. Antidepressant usage was common in patients with ALD (47.4%) and NAFLD (40.8%). After adjusting for covariates, MDD (adjusted hazard ratio [AHR]: 0.80, 95% CI: 0.63-1.02 for NAFLD; and AHR 1.01, 0.88-1.15 for ALD) was not associated with improved decompensated cirrhosis-free survival. The antidepressant mirtazapine was associated with worse decompensated cirrhosis-free survival among NAFLD (AHR 2.16, 95% CI: 1.32-3.52) and ALD (AHR 1.53, 1.09-2.15) cohorts. Similarly, mirtazapine was associated with mortality in both cohorts.
MDD was not associated with worse outcomes for ALD or NAFLD. Mirtazapine was associated with an increased risk of decompensated cirrhosis or death, which was not observed with other antidepressants. Prospective studies are warranted to confirm these findings.
重度抑郁症和抗抑郁药的使用对慢性肝病患者的生存影响尚不清楚。我们评估了重度抑郁障碍(MDD)和抗抑郁药对酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD)患者生存的影响。
利用英国最大的医疗数据库——健康改善网络数据库,于 1986 年至 2017 年期间,确定了 4148 例 ALD 患者和 19053 例 NAFLD 患者。我们的主要结局是发展为失代偿性肝硬化或死亡。在多变量 Cox 比例风险模型中,将 MDD 和每类抗抑郁药作为时变协变量进行评估。模型调整了年龄、性别、社会经济地位和合并症。
ALD 患者的 MDD 发生率(22.8%)高于 NAFLD 患者(16.1%),P<0.01。ALD(47.4%)和 NAFLD(40.8%)患者均常使用抗抑郁药。在调整了协变量后,MDD(调整后的危险比 [AHR]:NAFLD 为 0.80,95%CI:0.63-1.02;ALD 为 1.01,0.88-1.15)与失代偿性肝硬化无进展生存率的提高无关。抗抑郁药米氮平与 NAFLD(AHR 2.16,95%CI:1.32-3.52)和 ALD(AHR 1.53,1.09-2.15)患者的失代偿性肝硬化无进展生存率恶化有关。同样,米氮平与这两个队列的死亡率相关。
MDD 与 ALD 或 NAFLD 的不良结局无关。米氮平与失代偿性肝硬化或死亡的风险增加有关,但其他抗抑郁药则没有观察到这种情况。需要前瞻性研究来证实这些发现。