ORIGINAL PAPERS

 

The Baveno VI criteria for predicting esophageal varices: validation in real life practice

 

 

Mafalda Sousa, Sónia Sousa Fernandes, Luísa Proença, Ana Paula Silva, Sónia Leite, Joana Silva, Ana Ponte, Jaime Rodrigues, João Carlos Silva and João Carvalho

Centro Hospitalar de Vila Nova de Gaia e Espinho. Vila Nova de Gaia, Portugal

Correspondence

 

 

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ABSTRACT

Background and aims: According to the Baveno VI consensus, patients with liver stiffness < 20 kPa and a platelet count > 150,000 ul have very low risk of clinically significant varices and do not need a screening endoscopy. The aim of this study was to evaluate non-invasive methods as predictors of esophageal varices according to the Baveno VI recommendations, in real life clinical practice.
Methods: Retrospective evaluation of patients with chronic liver disease who underwent transient elastography between January 2013 and December 2015.
Results: One hundred and four patients were included in the study, the median age was 56.8 years and 69.2% were male. The etiology of liver disease was hepatitis C in 80% of patients (including 20% with HIV co-infection), alcohol in 12%, hepatitis B in 4% and other causes in 5%. Varices were present in 25% of patients. A liver stiffness < 20 kPa had a sensitivity of 92.3% and a specificity of 84.6%. When considering high risk varices (small with red wales or large varices), a liver stiffness < 20 kPa had 100% sensitivity. A platelet count > 150,000/l had a sensitivity of 84.6% and a specificity of 64.1%. Four patients with a platelet count (PLT) > 150,000/l had esophageal varices. When both criteria were applied to the patient cohort, according to the Baveno VI consensus, the sensitivity was 100% and the specificity, 61.5%.
Conclusion: In this study, the Baveno VI criteria had 100% sensitivity but a relatively low specificity for the non-invasive diagnosis of esophageal varices. In clinical practice, all patients with varices are identified but many patients have a subsequent negative endoscopy.

Key words: Baveno VI. Esophageal varices. Non-invasive.

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Introduction

Gastroesophageal varices are a common consequence of portal hypertension in cirrhotic patients. The prevalence is approximately 50% and is correlated with liver disease severity. Varices develop at a rate of 7-8% per year and progression from small to large varices occurs at a rate of 10-12% per year. Variceal hemorrhage occurs at a yearly rate of 5% and is associated with a high mortality rate (15-25% at six weeks) (1,2). Prophylactic therapy with beta-blockers or elastic band ligation is recommended in patients with high risk varices (small varices with red wale marks or large varices). Esophagogastroduodenoscopy is the gold-standard to determine the presence and size of varices. However, it is an invasive and expensive procedure with associated risks (3).

There is substantial evidence indicating that transient elastography (TE) can detect patients with a high risk of a clinically significant elevation of the hepatic venous pressure gradient (HVPG) or varices. (3) According to a recent meta-analysis, the diagnostic performance of TE for the prediction of clinically significant portal hypertension (HVPG > 10 mmHg) in the setting of compensated chronic liver disease or cirrhosis is excellent, with an AUROC of 0.93. (4) A correlation between liver stiffness values (LSV) and the presence of esophageal varices has also been reported in several studies with AUROCs ranging from 0.74 to 0.85 and LSV cut-offs from 13.9 to 21.5 kPa (5-11). Although the sensitivity for the prediction of esophageal varices was high (76-95%), the specificity was poor (43-78%).

A meta-analysis from 2016 of 20 studies (2,994 patients) showed sensitivity, specificity and positive and negative likelihood ratios of TE for the prediction of large varices of 0.81 (95% confidence interval [CI], 0.79-0.84), 0.71 (95% CI, 0.69-0.73), 2.63 (95% CI, 2.15-3.23) and 0.27 (95% CI, 0.22-0.34), respectively, although there was some heterogeneity among the studies (12). In routine clinical practice, TE may have some limitations in patients with a larger abdominal circumference, ascites and physiological or pathological processes associated with liver congestion. In addition, this technique is well validated in viral hepatitis but not in other chronic liver diseases (3).

Other non-invasive tools have been proposed for the detection of esophageal varices, including routine biological parameters such as platelet count, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (13-15).

The Baveno VI criteria combines TE and platelet count for the prediction of the risk of varices. Patients with an LSV under 20 kPa and a platelet count over 150,000/ul are at a low risk of having varices requiring treatment and, therefore, do not require a screening endoscopy (16).

The aim of this study was to validate the Baveno VI criteria in patients with chronic liver disease in order to determine its sensitivity in terms of the ability to rule out the presence of esophageal varices.

 

Patients and methods

This was a single center retrospective study of patients with chronic liver disease who had undergone a TE between January 2013 and December 2015. Patients were included in the study if laboratory tests and upper endoscopy were performed within a maximum of 12 months of the TE. Exclusion criteria included decompensated cirrhosis (defined as a Child-Pugh C score or past history of ascites, encephalopathy or variceal hemorrhage) and non-cirrhotic portal hypertension.

TE was performed by experienced practitioners after at least four hours of fasting. LSV were measured in the right lobe of the liver and ten valid measurements were obtained for each patient, in order to generate a median LSV value. With regard to patients who underwent more than one TE during the study period, the higher liver stiffness value was considered.

Laboratory parameters were collected, including AST, ALT, bilirubin, platelet count and the International Normalized Ratio (INR). Esophageal varices identified via endoscopy were classified according to the Baveno VI consensus. Small varices with red wale marks or large varices were considered as high risk.

Statistical analysis

Statistical analysis was performed using the SPSS package version 20 (SPSS Inc., Chicago, IL, USA). Comparisons between groups were performed using the Chi-squared test for categorical variables or the Student's t test for continuous variables. Multivariate analysis was performed via logistic regression. Statistical significance was set at p < 0.05. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were also calculated.

 

Results

One hundred and four patients were included in the study. The mean age of the cohort was 57 years and the majority of patients were male. The demographic and clinical characteristics of the cohort are summarized in table 1.

 

 

The main etiology of liver disease in the study group was hepatitis C (80% of patients and 20% with HIV co-infection). Other etiologies included alcoholism (12%), hepatitis B (4%) and other causes (5%). Varices were present in 25% of patients and were classified as small in 18% and large in 7% of cases. High risk varices, i.e., small varices with red wales or large varices, were present in 9% of the study population. There were statistically significant differences in AST (p = 0.004), ALT (p = 0.002), platelet count (p = 0.046) and liver stiffness (p = 0.004) between patients with and without varices (Table 2). Only liver stiffness was an independent predictor of varices (p < 0.001) according to the multivariate analysis.

 

 

A LSV under 20 kPa had a sensitivity of 92.3% and a specificity of 84.6% for the prediction of varices. Only two patients with a LSV < 20kPa had esophageal varices. Twenty-four of the 36 patients with a LSV > 20 KPa had varices (Table 3). A platelet count > 150,000/ul had a sensitivity of 84.6% and a specificity of 64.1% for the prediction of varices. Four patients with a platelet count > 150,000/ul had esophageal varices. Fifty patients had a platelet count < 150,000/ul and only 22 had varices (Table 3).

 

 

When both criteria were applied to the patient cohort according to the Baveno VI consensus, the sensitivity was 100% and the specificity was 61.5% for the detection of esophageal varices. The negative and positive predictive values were 100% and 46%, respectively. Thus, all patients with varices were correctly identified (n = 26), although 30 underwent a negative endoscopy (Table 3). The subgroup of HIV-Hepatitis C co-infected patients (n = 15) had a lower specificity (33%). When only high risk varices were considered, TE sensitivity and specificity were 100% and 72%, platelet count was 89% and 56% and Baveno VI was 100% and 50%, respectively.

 

Discussion

The possibility to predict varices by non-invasive methods is important in order to avoid unnecessary endoscopies, thus saving time, costs and possible risks associated with the procedure. In this study, the Baveno VI criteria had a 100% sensitivity, with a negative predictive value of 100% but a relatively low specificity for the non-invasive diagnosis of esophageal varices. In practical terms, this technique identifies all patients with varices, although many would undergo an endoscopy with a negative result. The specificity of the Baveno VI criteria was lower than TE alone since the platelet count is reduced in liver cirrhosis due to different reasons, including portal hypertension (via hypersplenism), antibody-mediated platelet destruction (mostly in viral hepatitis), decreased thrombopoietin production and myelotoxic effects of alcohol and the hepatitis virus (14).

The recent retrospective study by Maurice et al. (17), which included 310 patients, reported a sensitivity of 87% for the Baveno VI criteria, and only two patients with high risk varices were missed. One patient had undergone a splenectomy and the exclusion of this patient would have resulted in an improved sensitivity. Two additional retrospective studies (Jangouk et al. [18] and Llop et al. [19]) validated non-invasive methods for the detection of esophageal varices, including the Baveno VI criteria, and showed a sensitivity of 100% (161 patients) and a specificity of 88% (161 patients).

These results support the application of the Baveno VI criteria in clinical practice and that a low proportion of patients with varices would be misclassified. In the event that patients with varices are missed, TE and platelet count are repeated on a yearly basis. Thus, if liver stiffness increases or the platelet counts declines, an upper endoscopy is performed, which in turn reduces the chance of missing cases for more than one year. The ideal screening strategy should be non-invasive, widely available and inexpensive in order to impact on health systems. However, this is not the case in many developing countries, as the equipment for the TE measurement is scarcely available and the test is expensive (20).

The main limitations of this study include the fact that it is a retrospective, single center study. In addition, there was a low prevalence of high risk varices, and upper endoscopy was not performed simultaneously with TE.

In conclusion, this study validates and confirms previous data that suggest that the Baveno VI recommendations can be safely used in clinical practice. However, these criteria should be validated in different cohorts that include different etiologies of chronic liver disease, and the prevalence of varices is also an important issue to be considered.

 

References

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Correspondence:
Mafalda Sousa.
Centro Hospitalar de Vila Nova de Gaia e Espinho.
Vila Nova de Gaia, Portugal
e-mail: mafalda_m_p_sousa@hotmail.com

Received: 16-05-2017
Accepted: 26-06-2017