Research ArticleThe CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure
Introduction
Patients with cirrhosis who require admission to hospital with acute decompensation (AD) (ascites, gastrointestinal bleeding, hepatic encephalopathy and/or acute bacterial infections) have widely variable prognosis dependent on whether they have acute-on-chronic liver failure (ACLF) [1], [2], [3], which is diagnosed using the CLIF Consortium organ failure score (CLIF-C OFs) [4], [5]. In the CANONIC study, which was performed in patients with AD of cirrhosis with and without ACLF, the 3-month mortality of patients with ACLF was 51% [5]. A specific score to predict prognosis in patients with ACLF, the CLIF-C ACLF score (CLIF-C ACLFs) has been developed [3].
In the CANONIC patients with AD who did not develop ACLF, the 28-day mortality was 4.6%, but this increased to 12.6% at 3-month, 18.3% at 6 months, and 27.6% at 1-year (AD patients) [5]. These data suggest that some patients with AD are also at high risk of short-term mortality; they should be recognised early and treated as potentially high-risk patients requiring closer monitoring and interventions to prevent progression to ACLF and death. On the other hand, patients with AD who are at low risk of mortality may be discharged early, potentially saving resources and distress for the patients and their relatives. At present a specific prognostic score focussing on AD patients is an unmet need [2], [6]. Therefore, the main objective of this study was to develop a new score (CLIF-Consortium score for AD patients, CLIF-C ADs) with a higher prognostic accuracy than the currently used scoring systems such as MELDs [7], MELD-Nas [8], and Child-Pugh score (CPs) [9]. The study had three main aims. First, to develop a scoring system for sequential use based on clinical and biochemical data to prognosticate survival of AD patients who did not fulfil criteria for the diagnosis of ACLF (CLIF-C ADs) [5]. Second, to compare the prognostic accuracy of CLIF-C ADs with MELDs, MELD-Nas, and CPs. Third, to validate the prognostic accuracy of the CLIF-C ACLFs in two prospective external cohorts of hospitalized cirrhotic patients with AD and no ACLF. We used the CANONIC study database to develop this score because it had over 1000 prospectively included patients with AD that were followed for 1-year in multiple centres in Europe. The validation sets were drawn from hospitals in Barcelona (Hospital Clinic) and London (Royal Free Hospital).
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Study populations
The study was performed in cirrhotic patients with AD from two different populations. The CANONIC study population included 1349 cirrhotic patients from 29 European hospitals who had developed AD leading to hospitalization, and were prospectively followed-up to 1-year. Reasons for exclusion were: patients with decompensated cirrhosis admitted for a scheduled procedure or treatment, patients with hepatocellular carcinoma outside Milan criteria, severe chronic extra-hepatic disease, HIV infection
Study populations
The derivation set included 1016 of the 1349 CANONIC study patients who did not present ACLF at study enrolment and had all the data required to compute the studied scores [3], [5]. The etiology of cirrhosis was mainly alcoholic or chronic hepatitis C (80%, Table 1). In the remaining patients, the causes of cirrhosis were chronic hepatitis B (67 patients, 6.6%), cryptogenic (61, 6.0%), NASH (55, 5.4%), primary biliary cirrhosis (24, 2.4%) and other causes. Among the 67 patients with HBV, 29
Discussion
The present study used the data acquired in the CANONIC study [3], [5] to focus on a group of patients with acutely decompensated cirrhosis with no ACLF, and has generated a validated new score, the CLIF-AD score, which can be used to prognosticate survival of these patients on the medium (3–6 months) and long term (1 year). The score also shows that it retains its accuracy when it is updated sequentially suggesting that the score responds to potential clinical interventions that may affect
Financial support
The CLIF Consortium is supported by an unrestricted grant from Grifols. Rajiv Jalan is supported by a comprehensive biomedical research center, UK grant; Richard Moreau was supported by an INSERM-APHP fellowship and Jonel Trebicka by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57 project 18).
PG received a grant from the Fondo de Investigación Sanitaria Carlos III – co financed by FEDER: FIS_PI12/330.
Conflict of interest
Rajiv Jalan received research funding from Vital Therapies, has served on Scientific Advisory Board for Conatus Pharma, and received lecture fees from Gambro and has on-going research collaboration with Gambro, Grifols and is the Principal Investigator of an Industry sponsored study (Sequana Medical). He is also the inventor of a drug, L-ornithine phenylacetate, which UCL has licensed to Ocera Therapeutics. Faouzi Saliba has received speaker honorarium and/or grant research from Novartis,
Authors’ contributions
RJ, FS, VA: study design, data evaluation, manuscript writing and final review; MP, AA: study design, statistical analysis, manuscript writing and review; RM, PG, MB: study design and final manuscript review; JF, PHF, RS, RM, PC, FD, PA, CA, WL, JT, DS, SZ, TG, AG, JW: patient recruitment, data collection and final manuscript review.
The EASL-CLIF Consortium
It is a network of 63 European university hospitals, aimed at stimulating research on pathophysiology, diagnostic and treatment on Chronic Liver Failure. During the period 2009–2012 the EASL-CLIF Consortium had received unrestricted grants from Grifols and Gambro. Grifols has prolonged its unrestricted grant for an additional period of four years. There is no other support for the Consortium. The Fundació Clinic, a foundation ruled by the Hospital Clinic and University of Barcelona, administers
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The complete list of CANONIC Study Investigators is reported at the end of the manuscript.