Research ArticleRefining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease
Graphical abstract
Introduction
The Baveno VI consensus introduced the term “compensated advanced chronic liver disease (cACLD)” to describe the spectrum of advanced fibrosis and cirrhosis in asymptomatic patients, who are at risk of developing clinically significant portal hypertension (CSPH).1 Despite the absence of symptoms and/or clinical signs, patients with cACLD are at high risk of future liver-related morbidity and mortality.1 Consequently, early diagnosis and subsequent prompt interventions may improve clinical outcomes in these patients.2
In order to diagnose cACLD in the large group of patients with asymptomatic liver disease, the Baveno VI consensus suggested that transient elastography (TE) is sufficient to suspect cACLD, since it has good diagnostic accuracy and is also a safe, painless, fast and relatively low-cost non-invasive diagnostic method.1 Liver stiffness (LS) values <10 kPa were proposed as a safe cut-off for excluding the presence of cACLD and LS values >15 kPa as highly suggestive of cACLD.
The dual cut-off approach for TE was seldom used until the Baveno VI recommendations. TE has been mostly studied as a single cut-off diagnostic test, with optimal cut-offs derived in most studies from post hoc analyses.3 Therefore, reported cut-offs for the diagnosis of specific fibrosis stages vary, sometimes significantly, amongst studies.4,5 Moreover, it is unlikely that the same cut-offs for a specific fibrosis stage apply to different liver disease aetiologies.4,6 The use of dual cut-offs may overcome both these limitations and introduce uniformity in the diagnosis of chronic liver disease. The Baveno VI criteria for screening varices needing treatment1 have already been validated in several small to medium independent cohorts[7], [8], [9], [10] and in a recent large meta-analysis of 30 studies.11 However, the criteria to rule in and out cACLD have not been externally validated in a real-world population until now.
Herein, we aimed to assess the diagnostic accuracy of the LS dual cut-off (<10 and >15 kPa) as a standalone test for the exclusion and diagnosis of cACLD (defined as the presence of advanced fibrosis or ≥F3), as proposed by the Baveno VI criteria,1 in a multicentre validation study of real-world data. Secondary aims were to explore optimal alternative rule in/rule out cut-offs with a target specificity and sensitivity of ≥90% and to derive a risk model for predicting cACLD in unclassified patients.
Section snippets
Study population
This study included 5,648 adult patients followed in 10 liver centres in Europe (Bordeaux n = 1,335 [24%], Cluj n = 1,180 [21%], Palermo n = 808 [14%], Angers, n = 698 [12%], Heidelberg 450 [8%], Firenze n = 334 [6%], Odense, n = 316 [6%], London n = 303 [5%], Athens n = 154 [3%], Beaujon n = 70 [1%]). The study population included patients with all fibrosis stages and no previous decompensation who had chronic hepatitis B (CHB), chronic hepatitis C (CHC), non-alcoholic fatty liver disease
Patient characteristics
Our study included 5,648 patients from 10 centres; mean age was 51 ± 13 years and 3,016 (53%) were males. The main patient characteristics are presented in Table 1. The most common cause of liver disease was CHC (52%) followed by NAFLD (19%), ALD (17%) and CHB (13%). The majority (66%) of patients with valid TE measurements (n = 5,483) had LS <10 kPa, while 18% of patients had LS >15 kPa. Furthermore, 7% of the TE results were evaluated as “poorly reliable” and 27% were considered as “very
Discussion
This is the first large study to validate the LS thresholds recommended by the Baveno VI consensus1 for diagnosing or ruling out cACLD in asymptomatic patients with chronic liver disease. We included over 5,600 patients from 10 centres across Europe. Our study showed that the proposed cut-offs of <10 and >15 kPa have moderate sensitivity (75%) and very high specificity (96%) for ruling out and diagnosing cACLD, respectively. Thus, we propose the adoption of lower dual cut-offs at <7 and >12
Financial support
The study in Odense University Hospital received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 668031, the Challenge Grant “MicrobLiver” number NNF15OC0016692 from the Novo Nordisk Foundation, Innovation Fund Denmark and the free research funds for Odense University Hospital and Region of Southern Denmark.
Authors’ contributions
Margarita Papatheodoridi: Data analysis, study design, primary authorship. Jean Baptiste Hiriart: Data collection. Monica Lupsor-Platon: Data collection, revision for important intellectual concepts. Fabrizio Bronte: Data collection. Jerome Boursier: Data collection, revision for important intellectual concepts. Omar Elshaarawy: Data collection. Fabio Marra: Data collection, revision for important intellectual concepts. Maja Thiele: Data collection, revision for important intellectual concepts.
Data availability statement
The data that support the findings of this study are available from the corresponding author, upon reasonable request
Conflicts of interest
Victor de Ledinghen reports consultancy for Echosens and SuperSonic Imagine. All other authors have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.
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These two authors had equal contribution to the manuscript and are joint senior authors.