School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.
Public Health Scotland, Glasgow, UK.
BMJ. 2023 Aug 2;382:e074001. doi: 10.1136/bmj-2022-074001.
To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population.
Population based cohort study.
British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only).
21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019.
Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates.
1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates.
Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.
量化在无干扰素直接作用抗病毒药物时代成功治疗丙型肝炎患者的死亡率,并将这些死亡率与一般人群进行比较。
基于人群的队列研究。
不列颠哥伦比亚省、苏格兰和英格兰(英格兰队列仅包括肝硬化患者)。
21790 名在无干扰素抗病毒药物时代成功治疗丙型肝炎的患者(2014-19 年)。参与者被分为三组肝脏疾病严重程度:无肝硬化(肝硬化前)、代偿性肝硬化和终末期肝病。随访从抗病毒治疗完成后 12 周开始,截止日期为死亡日期或 2019 年 12 月 31 日。
粗死亡率和年龄性别标准化死亡率,以及与一般人群相比的标准化死亡率比,调整年龄、性别和年份。使用泊松回归确定与全因死亡率相关的因素。
1572 名(7%)参与者在随访期间死亡。主要死亡原因是药物相关死亡率(n=383,24%)、肝功能衰竭(n=286,18%)和肝癌(n=250,16%)。不列颠哥伦比亚省、苏格兰和英格兰的全因死亡率(每 1000 人年死亡人数)分别为 31.4(95%置信区间 29.3 至 33.7)、22.7(20.7 至 25.0)和 39.6(35.4 至 44.3)。所有疾病严重程度组和所有研究地点的全因死亡率均明显高于一般人群;例如,不列颠哥伦比亚省无肝硬化患者的全因死亡率高 3 倍(标准化死亡率比 2.96,95%置信区间 2.71 至 3.23;P<0.001),不列颠哥伦比亚省终末期肝病患者的全因死亡率高 10 倍以上(13.61,11.94 至 15.49;P<0.001)。在回归分析中,年龄较大、近期药物滥用、酒精滥用和合并症与较高的死亡率相关。
在无干扰素、直接作用抗病毒药物时代成功治疗丙型肝炎的患者的死亡率与一般人群相比仍然较高。药物和肝脏相关死亡原因是导致死亡率过高的主要原因。这些发现强调了在成功治疗丙型肝炎后需要继续提供支持和随访,以最大限度地提高直接作用抗病毒药物的效果。