Background

Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables.

Methods

In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest.

Findings

Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61–2·84]) and from LICs or LMICs (2·54 [1·82–3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44–2·65] in UMICs and 1·84 [1·24–2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24–0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10–0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39–0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11–0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically.

Interpretation

Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes.

Funding

National Institutes of Health and US Department of Veterans Affairs.

中文翻译：

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肝硬化住院患者死亡率和肝移植的全球差异：CLEARED 联盟的一项前瞻性队列研究

 背景

肝硬化是肝损伤的最终结果，在全球范围内死亡率很高。国家层面的收入对肝硬化死亡率的影响尚不清楚。我们旨在利用专注于肝硬化相关和访问相关变量的全球联盟来评估肝硬化住院患者死亡的预测因素。

 方法

在这项前瞻性观察队列研究中，CLEARED 联盟对六大洲 25 个国家的 90 家三级护理医院的肝硬化住院患者进行了随访。连续入组的年龄超过 18 岁、非选择性入院、无 COVID-19 或晚期肝细胞癌的患者。我们将每个中心的注册人数限制为最多 50 名患者，以确保公平参与。数据是从患者及其病历中收集的，包括人口统计特征；国家;疾病严重程度（MELD-Na评分）；肝硬化原因；使用的药物；入学理由；移植清单；过去6个月内有肝硬化相关病史；住院期间和出院后 30 天的临床病程和管理。主要结局是住院期间或出院后 30 天内死亡和接受肝移植。对各地点进行了有关诊断和治疗服务的可用性和可及性的调查。结果按参与地点的国家收入水平进行比较，根据世界银行收入分类（高收入国家 [HIC]、中高收入国家 [UMIC] 和低收入或中低收入国家 [LIC]或中低收入国家]）。使用控制人口变量、疾病原因和疾病严重程度的多变量模型来分析与感兴趣的变量相关的每个结果的几率。

 发现

患者于2021年11月5日至2022年8月31日期间招募。获得了3884名患者的完整住院数据（平均年龄55·9岁[SD 13·3]；2493名（64·2%）男性和1391名（35·35·9岁）男性。 8%) 女性；1413 名 [36·4%] 来自高收入国家，1757 名 [45·2%] 来自中低收入国家，714 名 [18·4%] 来自低收入国家或中低收入国家，其中 410 名在术后 30 天内失访出院。高收入国家中住院期间死亡的患者人数为 1413 人中的 110 人 (7·8%)，中低收入国家 1757 人中的 182 人 (10·4%)，低收入国家和中低收入国家 714 人中的 158 人 (22·1%) (p< 0 id=9> 与 HIC 相比），以及 714 名来自 LIC 和 LMIC 的 714 名患者中的 14 名 (2·0%) (0·21 [0·10–0·41] vs HIC) 在指数住院期间 (p<0 id=11>出院后 30 天，来自低收入国家或中低收入国家的 509 名患者中有 16 名 (3·1%) (0·21 [0·11–0·40]相对于高收入国家) (p<0·0001)。现场调查结果显示，获得重要药物（利福昔明、白蛋白和特利加压素）和干预措施（急诊内窥镜检查、肝移植、重症监护和姑息治疗）的情况因地理位置而异。

 解释

无论医疗风险因素如何，低收入国家、中低收入国家或中低收入国家的肝硬化住院患者的死亡率显着高于高收入国家的住院患者，这可能是由于获得基本诊断和治疗服务的机会差异所致。这些结果应该鼓励研究人员和政策制定者在评估肝硬化相关结果时考虑获得服务和药物。

 资金

美国国立卫生研究院和美国退伍军人事务部。