Unit of Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Institute of Biomedicine of Seville and University of Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
Unit for the Clinical Management of Digestive Diseases, Valme University Hospital, Sevilla, Spain.
J Hepatol. 2018 May;68(5):940-948. doi: 10.1016/j.jhep.2017.12.019. Epub 2017 Dec 28.
BACKGROUND & AIMS: Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model.
This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes.
A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%-3%) and high-risk (≥25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups.
The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy.
The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.
患有晚期肝纤维化的患者仍有发生肝硬化相关结局的风险，而患有严重合并症的患者可能无法从丙型肝炎（HCV）清除中获益。我们旨在收集直接作用抗病毒治疗的前两年内全因死亡率和相关临床事件的数据，同时确定基于合并症的模型的预后能力。
这是一项前瞻性非干预性研究，从直接作用抗病毒治疗开始到发生感兴趣的事件（死亡率）或随访两年，包括 14 家西班牙大学医院。纳入患有 HCV 感染的患者，无论肝纤维化阶段如何，只要接受直接作用抗病毒治疗，就会被用于构建估计和验证队列。根据 Charlson 合并症指数和 CirCom 指数评估合并症。
在第一年，共有 3.4%（65/1,891）的患者死亡，而在研究期间，有 5.4%（102/1,891）的患者死亡。在校正肝硬化、血小板计数、丙氨酸氨基转移酶和性别后，以下因素与一年死亡率独立相关：Charlson 指数（风险比[HR] 1.55；95%CI 1.29-1.86；p=0.0001）、胆红素（HR 1.39；95%CI 1.11-1.75；p=0.004）、年龄（HR 1.06 95%CI 1.02-1.11；p=0.005）、国际标准化比值（HR 3.49；95%CI 1.36-8.97；p=0.010）和白蛋白（HR 0.18；95%CI 0.09-0.37；p=0.0001）。HepCom 评分显示出良好的校准和区分度（C 统计量 0.90），并且在一年和两年死亡率方面优于其他预后评分（终末期肝病模型 0.81、Child-Pugh 0.72、CirCom 0.68）。HepCom 评分确定了低危（≤5.7 分：2%-3%）和高危（≥25 分：56%-59%）死亡率组，在估计和验证队列中均如此。各组之间临床事件的分布相似。
HepCom 评分，一种结合 Charlson 合并症指数、年龄和肝功能（国际标准化比值、白蛋白和胆红素）的评分，可以检测出一组患者在开始直接作用抗病毒治疗后，有一年和两年死亡率以及相关临床事件的高风险。
患有严重合并症的患者可能无法从 HCV 病毒清除中获益。需要一种决定谁将从治疗中受益的算法来更好地管理慢性 HCV 感染。
