Abstract
In Baveno I–V conferences, it was recommended that all patients with cirrhosis should have a gastroscopy to screen for varices. In 2015, as a consequence of the high development in noninvasive tests, Baveno VI consensus recommended that patients with a liver stiffness <20 kPa and platelet count >150,000 could avoid endoscopy, since the risk of finding high-risk varices in these patients was very low, less than 5%. These became known as the Baveno VI criteria and were validated in a large number of studies in the last 6 years. This chapter analyses the data validating Baveno VI criteria, discusses whether these criteria could be expanded, and explores other potential methods to select patients in need for endoscopy.
Access provided by Autonomous University of Puebla. Download conference paper PDF
Similar content being viewed by others
Keywords
- Baveno VI criteria
- Validation
- Liver stiffness
- Platelet count
- Gastroesophageal Varices
- Screening endoscopy
The Baveno VI Criteria
The first five Baveno consensus conferences recommended performing endoscopy on every patient with a diagnosis of cirrhosis. For the first time, Baveno VI conference introduced a two-step strategy for the screening of esophageal varices in patients with compensated advanced chronic liver disease (cACLD), establishing what became known as the Baveno VI criteria [1]. These resulted from the combination of a liver stiffness measurement by transient elastography (LSM by TE) of less than 20 kPa, together with a platelet count over 150 × 109/L. The risk of high-risk varices (HRV) when fulfilling both criteria was considered low enough to circumvent the performance of an endoscopy. In those patients outside Baveno VI criteria, an endoscopy should be performed. These criteria have been widely adopted in practice and recommended by subsequent guidelines for the management of a chronic liver disease [2]. Furthermore, since the Baveno VI conference, the criteria have undergone an unprecedented level of validation, with 28 fully published manuscripts up to March 2021 testing its performance.
The basic tenet of the proposal at Baveno VI was that “for high risk varices (HRV: medium-large varices or small with red signs) the acceptable risk of missing varices should be near 0 or 5% at the most”) [3]. This put the emphasis on not missing an opportunity of doing primary prophylaxis of bleeding (either with beta-blockers or variceal ligation), and considered much less harmful the performance of an unneeded endoscopy since the invasiveness of endoscopy is low. Indeed, setting that threshold at the 5% level means that we would accept to do an endoscopy with up to 95% chance of a false-positive result, and up to 5% chance of a false-negative result, or what would be equivalent to the value of not missing a case of HRV (a false negative) was 19 (95/5) times greater than the value of doing an unneeded endoscopy (false positive).
The subsequent ANTICIPATE study showed that the pointwise estimate of a combination of LSM by TE of 20 kPa and a platelet count of 150 × 109/L corresponds to the predicted risk of HRV of ~5% [4]. The Baveno VI criteria, therefore, set the maximum allowed risk of missing varices at the 5% mark (Fig. 10.1). Provided that the ANTICIPATE model is well calibrated, the negative predicted value (NPV) of the criteria would tend to be >95%, since all patients with negative criteria would have a theoretical risk of HRV below 5%. This seems very reasonable in a two-step strategy where, in the first step, a high NPV is favored.
The interpretation of the 5% threshold raised some questions [5], including whether this should correspond to a sensitivity of >95% for the criteria or a NPV of >95%. It is important to emphasize that sensitivity is a backward probability. For example, the sensitivity of the Baveno VI criteria would be the probability of having positive criteria provided the patient has HRV. Therefore, sensitivity never reflects a clinical question, but might be relevant in the early development of a diagnostic test, especially when the study is based on a case-control study. The NPV better reflects the clinical question addressed here: what would be the probability of not having HRV provided that the patient has values within the Baveno VI criteria.
Evolving recommendations for the management of compensated cirrhosis, based on the result of the PREDESCI study [6] might result in the use of beta-blockers in patients with clinically significant portal hypertension (CSPH), regardless of the presence of varices. This shift in paradigm, if widely adopted, will decrease the relevance of Baveno VI criteria for the assessment of varices, since patients already on beta-blockers do not require endoscopy. However, a relevant proportion of patients would have either contraindications or intolerance to beta-blockers, and these patients would require endoscopic assessment unless they are within the Baveno VI criteria.
Validation of Baveno VI Criteria
We performed a systematic search of fully published studies up to March 2021 assessing the performance of Baveno VI criteria. The search strategy is reported in detail in supplementary data 11.1. We identified 28 studies, of which the main characteristics are reported in Table 10.1.
We performed a univariate quantitative meta-analysis of proportions to pool NPVs since, as discussed above, this is the metric we consider the benchmark for validation of the performance of the criteria. The forest plot is shown in Fig. 10.2, with further methodological details in the figure legend. The pooled NPV was 0.99 (95% CI 0.99–1.00), with no significant heterogeneity. The proportion of saved endoscopies ranged from 8% to 60%. The interpretation of the proportion of saved endoscopies must be taken with caution, since they are highly dependent on the spectrum of diseases assessed in individual studies. Results of the meta-analysis of sensitivity are provided in supplementary data 11.2 (pooled sensitivity 0.99; 95% CI 0.98–0.99). We did not use bivariate models (which take into account the covariance of sensitivity and specificity) in our meta-analysis for two reasons. First, bivariate models require continuity correction, which adds a 0.5 to cells with a zero value. Since the number of zero cells was high (a number of studies had a sensitivity of 100% or an NPV of 100%), adding that 0.5 would artificially bring down sensitivity and NPV. Second, as detailed above, Baveno VI is meant to be used in the first step of the approach to diagnosing varices, so the main goal is a high NPV, and positive predictive value and specificity have much less relevance.
Impact of Etiology on the Performance of Baveno VI Criteria
Even if there was no heterogeneity in the NPVs of Baveno VI across studies, to confirm that Baveno VI criteria perform well across etiologies, we conducted a subgroup meta-analysis. Only 12 of the 28 studies performed etiology-specific analysis. Figure 10.3 demonstrates the forest plot of the studies. There were no significant differences in NPVs according to etiology subgroups.
Can Baveno VI Criteria Be Expanded?
The Baveno VI criteria is undoubtedly a validated tool to select for low-risk cACLD patients who can safely avoid a surveillance gastroscopy. However, it has been suggested that the number of saved endoscopies is low. As stated above, this is an unsound metric to compare different studies since it largely depends on how early in the natural history of cACLD these criteria are applied.
In an attempt to increase the proportion of saved endoscopies, the Expanded Baveno VI criteria were proposed after the Baveno VI conference, in which the LSM by TE threshold was increased to 25 kPa, and the platelet threshold decreased to 110 × 109/L [7]. A systematic search identified 16 studies assessing the expanded Baveno VI criteria, and results are shown in Fig. 10.4. Pooled NPV was 0.97 (95% CI 0.95–0.98). However, distinct from Baveno VI criteria, performance of Expanded Baveno VI showed significant heterogeneity (p < 0.0001). Results of the meta-analysis of sensitivities are provided in Supplementary data 11.3 (pooled sensitivity 0.90; 95% CI 0.87–0.93).
To address the sources of heterogeneity, we first evaluated whether etiology was associated with different performance of the expanded criteria. Eight studies showed etiology-specific data. Subgroup meta-analysis did not show any differences in performance across etiologies (Fig. 10.5).
We then evaluated the impact of the prevalence of HRV on the performance of Expanded Baveno VI criteria. The group of patients within the Expanded Baveno VI criteria comprises those who are within Baveno VI, and those beyond Baveno VI. The latter is the group that either shows a LSM of 20–25 kPa or a platelet count between 110 and 150. The pointwise risk of HRV of a LSM of 25 and a platelet count of 110 according to the ANTICIPATE model is ~12% [4]. Therefore, patients beyond Baveno VI but within Expanded Baveno VI would have a predicted risk of HRV between 5% and 12%. The prevalence of varices in patients within the Expanded Baveno VI criteria would depend largely on the distribution of the patients in those two groups (within Baveno VI and beyond Baveno VI). We therefore predicted that in series with higher prevalence of HRV, that would predictably have a higher number of patients beyond Baveno VI, the NPV of Expanded Baveno VI would decrease.
To assess this hypothesis, we performed a meta-regression analysis of NPV on the prevalence of HRV. There was a strong association between NPV and prevalence of HRV (Fig. 10.6a), with prevalence explaining 77% of the heterogeneity in NPVs observed across studies. There was no significant association between prevalence of HRV and the NPV of original Baveno VI (Fig. 10.6b), which is likely explained by the fact that all patients within Baveno VI have a theoretical <5% risk of HRV [4].
Other Elastography Methods and Baveno VI Criteria
Point shear wave elastography (pSWE) and 2D-SWE have witnessed increased use in the last few years [35]. The main unsolved issue with these methods is the multiplicity of devices with proprietary algorithms that lead to differences in the quantification of the speed of shear wave, and consequently provide values of liver stiffness that are not identical [34,35,36,37,39]. Therefore, the same liver stiffness thresholds defined for TE cannot be directly applied to pSWE or 2D-SWE [40].
Methods Beyond Baveno VI and Expanded Baveno VI Criteria
Several other models have been proposed for the noninvasive prediction of HRV, including the use of spleen stiffness, spleen diameter or blood-based tests, with only limited or no external validation. Several of these models are reviewed in specific chapters of the book.
Summary and Conclusions
The Baveno VI criteria have been extensively validated as a decision rule for not doing an endoscopy in patients with compensated cirrhosis. The pooled NPV in series with a wide range of prevalences of HRVs (from 5% to 33%) is 99% (95% CI 99%–100%). The expanded Baveno VI cannot be recommended at the present time in any etiology.
References
de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2010;53(4):762–8.
Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2017;65(1):310–35.
Augustin S, Pons M, Genesca J. Validating the Baveno VI recommendations for screening varices. J Hepatol. 2017;66(2):459–60.
Abraldes JG, Bureau C, Stefanescu H, Augustin S, Ney M, Blasco H, et al. Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the ‘Anticipate’ study. Hepatology. 2016;64(6):2173–84.
Calvaruso V, Cacciola I, Licata A, Madonia S, Benigno R, Petta S, et al. Is transient elastography needed for noninvasive assessment of high-risk varices? The REAL experience. Am J Gastroenterol. 2019;114(8):1275–82.
Villanueva C, Albillos A, Genescà J, Garcia-Pagan JC, Calleja JL, Aracil C, et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2019;393(10181):1597–608.
Augustin S, Pons M, Maurice JB, Bureau C, Stefanescu H, Ney M, et al. Expanding the Baveno VI criteria for the screening of varices in patients with compensated advanced chronic liver disease. Hepatology. 2017;66(6):1980–8.
Bae J, Sinn DH, Kang W, Gwak G-Y, Choi MS, Paik Y-H, et al. Validation of the Baveno VI and the expanded Baveno VI criteria to identify patients who could avoid screening endoscopy. Liver Int. 2018;38(8):1442–8.
Bellan M, Sainaghi PP, Minh MT, Minisini R, Molinari L, Baldrighi M, et al. Gas6 as a predictor of esophageal varices in patients affected by hepatitis C virus related-chronic liver disease. Biomark Med. 2018;12(1):27–34.
Calès P, Sacher-Huvelin S, Valla D, Bureau C, Olivier A, Oberti F, et al. Large oesophageal varice screening by a sequential algorithm using a cirrhosis blood test and optionally capsule endoscopy. Liver Int. 2018;38(1):84–93.
Colecchia A, Ravaioli F, Marasco G, Colli A, Dajti E, Di Biase AR, et al. A combined model based on spleen stiffness measurement and Baveno VI criteria to rule out high-risk varices in advanced chronic liver disease. J Hepatol. 2018;69(2):308–17.
Duan Z, Li L, Li J, Zhou S. Validation of the combined model based on platelet count and albumin to rule out high-risk varices in liver cirrhosis. Biomed Res Int. 2020;2020:5783748.
Gaete MI, Díaz LA, Arenas A, González K, Cattaneo M, Fuster F, et al. Baveno VI and Expanded Baveno VI criteria successfully predicts the absence of high-risk gastro-oesophageal varices in a Chilean cohort. Liver Int. 2020;40(6):1427–34.
Galizzi HO, Couto CA, Taranto DOL, Araújo SIO, Vilela EG. Accuracy of non-invasive methods/models for predicting esophageal varices in patients with compensated advanced chronic liver disease secondary to nonalcoholic fatty liver disease. Ann Hepatol. 2021;20:100229.
Jangouk P, Turco L, De Oliveira A, Schepis F, Villa E, Garcia-Tsao G. Validating, deconstructing and refining Baveno criteria for ruling out high-risk varices in patients with compensated cirrhosis. Liver Int. 2017;37(8):1177–83.
Kew GS, Chen ZJ, Yip AW, Huang YWC, Tan LY, Dan YY, et al. Identifying patients with cirrhosis who might avoid screening endoscopy based on serum albumin and bilirubin and platelet counts. Clin Gastroenterol Hepatol. 2021;19(1):199–201.e2.
Kotwal V, Mbachi C, Wang Y, Attar B, Randhawa T, Flores E, et al. A novel score to predict esophageal varices in patients with compensated advanced chronic liver disease. Dig Dis Sci. 2021;66(6):2084–91.
Lee HA, Kim SU, Seo YS, Lee Y-S, Kang SH, Jung YK, et al. Prediction of the varices needing treatment with non-invasive tests in patients with compensated advanced chronic liver disease. Liver Int. 2019;39(6):1071–9.
Matsui N, Imajo K, Yoneda M, Kessoku T, Honda Y, Ogawa Y, et al. Magnetic resonance elastography increases usefulness and safety of non-invasive screening for esophageal varices. J Gastroenterol Hepatol. 2018;33(12):2022–8.
Maurice JB, Brodkin E, Arnold F, Navaratnam A, Paine H, Khawar S, et al. Validation of the Baveno VI criteria to identify low risk cirrhotic patients not requiring endoscopic surveillance for varices. J Hepatol. 2016;65(5):899–905.
Moctezuma-Velazquez C, Saffioti F, Tasayco-Huaman S, Casu S, Mason A, Roccarina D, et al. Non-invasive prediction of high-risk varices in patients with primary biliary cholangitis and primary sclerosing cholangitis. Am J Gastroenterol. 2019;114(3):446–52.
Nawalerspanya S, Sripongpun P, Chamroonkul N, Kongkamol C, Piratvisuth T. Validation of original, expanded Baveno VI, and stepwise & platelet-MELD criteria to rule out varices needing treatment in compensated cirrhosis from various etiologies. Ann Hepatol. 2020;19(2):209–13.
Petta S, Sebastiani G, Bugianesi E, Viganò M, Wong VW-S, Berzigotti A, et al. Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis. J Hepatol. 2018;69(4):878–85.
Protopapas AA, Mylopoulou T, Papadopoulos VP, Vogiatzi K, Goulis I, Mimidis K. Validating and expanding the Baveno VI criteria for esophageal varices in patients with advanced liver disease: a multicenter study. Ann Gastroenterol. 2020;33(1):87–94.
Sharma S, Agarwal S, Gunjan D, Kaushal K, Anand A, Saraya A. Deciding among noninvasive tools for predicting varices needing treatment in chronic liver disease: an analysis of Asian cohort. Am J Gastroenterol. 2020;115(10):1650–6.
Silva MJ, Bernardes C, Pinto J, Loureiro R, Duarte P, Mendes M, et al. Baveno VI recommendation on avoidance of screening endoscopy in cirrhotic patients: are we there yet? GE Port J Gastroenterol. 2017;24(2):79–83.
Sousa M, Fernandes S, Proença L, Silva AP, Leite S, Silva J, et al. The Baveno VI criteria for predicting esophageal varices: validation in real life practice. Rev Esp Enferm Dig. 2017;109(10):704–7.
Stanislas DA, Constant A, Wilson NNA, Dimitri KH, Demba B, Anzouan-Kacou K, et al. Liver transient elastography combined to platelet count (Baveno VI) predict high esophageal varices in Black African patient with compensated hepatitis B related cirrhosis. Open J Gastroenterol. 2018;8(5):192–200.
Stefanescu H, Marasco G, Calès P, Fraquelli M, Rosselli M, Ganne-Carriè N, et al. A novel spleen-dedicated stiffness measurement by FibroScan® improves the screening of high-risk oesophageal varices. Liver Int. 2020;40(1):175–85.
Thabut D, Bureau C, Layese R, Bourcier V, Hammouche M, Cagnot C, et al. Validation of Baveno VI criteria for screening and surveillance of esophageal varices in patients with compensated cirrhosis and a sustained response to antiviral therapy. Gastroenterology. 2019;156(4):997–1009.e5.
Tosetti G, Primignani M, La Mura V, D’Ambrosio R, Degasperi E, Mezzina N, et al. Evaluation of three ‘beyond Baveno VI’ criteria to safely spare endoscopies in compensated advanced chronic liver disease. Dig Liver Dis. 2019;51(8):1135–40.
Wang H, Wen B, Chang X, Wu Q, Wen W, Zhou F, et al. Baveno VI criteria and spleen stiffness measurement rule out high-risk varices in virally suppressed HBV-related cirrhosis. J Hepatol. 2021;74(3):584–92.
Wong GL-H, Liang LY, Kwok R, Hui AJ, Tse Y-K, Chan HL-Y, et al. Low risk of variceal bleeding in patients with cirrhosis after variceal screening stratified by liver/spleen stiffness. Hepatology. 2019 Sep;70(3):971–81.
Stafylidou M, Paschos P, Katsoula A, Malandris K, Ioakim K, Bekiari E, et al. Performance of Baveno VI and expanded Baveno VI criteria for excluding high-risk varices in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17(9):1744–1755.e11.
Piscaglia F, Salvatore V, Mulazzani L, Cantisani V, Schiavone C. Ultrasound shear wave elastography for liver disease. A critical appraisal of the many actors on the stage. Ultraschall Med. 2016;37(1):1–5.
Cassinotto C, Lapuyade B, Guiu B, Marraud des Grottes H, Piron L, Merrouche W, et al. Agreement between 2-dimensional shear wave and transient elastography values for diagnosis of advanced chronic liver disease. Clin Gastroenterol Hepatol. 2020;18(13):2971–2979.e3.
Ronot M, Ferraioli G, Müller H-P, Friedrich-Rust M, Filice C, Vilgrain V, et al. Comparison of liver stiffness measurements by a 2D-shear wave technique and transient elastography: results from a European prospective multi-centre study. Eur Radiol. 2021;31(3):1578–87.
Conti F, Serra C, Vukotic R, Felicani C, Mazzotta E, Gitto S, et al. Assessment of liver fibrosis with elastography point quantification vs other noninvasive methods. Clin Gastroenterol Hepatol. 2019;17(3):510–517.e3.
Ferraioli G, De Silvestri A, Lissandrin R, Maiocchi L, Tinelli C, Filice C, et al. Evaluation of inter-system variability in liver stiffness measurements. Ultraschall Med. 2019;40(1):64–75.
Kang SH, Baik SK, Kim MY. Application of Baveno criteria and modified Baveno criteria with shear-wave elastography in compensated advanced chronic liver disease. J Korean Med Sci. 2020;35(30):e249.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Nature Switzerland AG
About this paper
Cite this paper
Bai, W.W.H., Abraldes, J.G. (2022). Varices and Screening Endoscopy. In: de Franchis, R. (eds) Portal Hypertension VII. Springer, Cham. https://doi.org/10.1007/978-3-031-08552-9_10
Download citation
DOI: https://doi.org/10.1007/978-3-031-08552-9_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-08551-2
Online ISBN: 978-3-031-08552-9
eBook Packages: MedicineMedicine (R0)