Introduction
Esophageal varices (EV) is a potentially lethal complication of liver cirrhosis. The prevalence of EV in cirrhotic patients is approximately 60–80%, and the 1-year rate of first variceal hemorrhage is approximately 12% [5% for low-risk varices and 15% for high-risk varices (HRV)] [
1‐
3]. The mortality of variceal bleeding ranges from 15 to 55% [
4]. Esophagogastroduodenoscopy (EGD) is usually recommended to identify those at risk of bleeding who should undergo prophylaxis treatment in patients with established cirrhosis [
5]. EGD is a costly invasive producer, which is not free of risks. More importantly, a large portion of patients undergoing EGD screening, particularly those with compensated advanced chronic liver disease (cACLD), do not have EV or only have low-risk varices [
6]. A relatively large proportion of EGDs is unnecessary according to current guidelines. Hence, there is a critical need to develop a noninvasive method to identify HRV and to spare unnecessary EGD screening.
For the past few years, non-invasive tests (NITs) have been established to triage patients for sparing EGDs. Elastography is the most widely used noninvasive method for screening HRV, especially transient elastography (TE). The ability of liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) by TE for identifying HRV has been widely evaluated. LSM < 20 kPa and platelet count (PLT) > 150 × 10
9/l can avoid EGD screening to identify HRV, which has been recommended by the Baveno VI consensus [
7]. More recently, some studies have suggested that SSM alone or together with LSM can avoid more EGDs [
8‐
10]. Although these methods can provide great diagnostic accuracy to diagnose HRV, they still have not been widely carried out in most liver centers, because of they rely on data that may not be readily available. TE is the most common technology for elastography, but is still not immediately available in all liver units, especially in developing countries. Therefore, creating an easy-to-use model to screen HRV and spare EGDs would be of great value to daily clinical work. Several easy-to-use models have been established. Calvaruso et al. have developed a model based on PLT and albumin (ALB) [
11]; Jangouk et al. reported a model based on PLT and MELD [
12].
In this study, we developed and validated an easy-to-use risk scoring system based on a routine laboratory test and routine liver Doppler ultrasonography to identify HRV and spare EGDs in patients with hepatitis B virus (HBV)-related cACLD. Meanwhile, we validated several reported easy-to-use models for screening HRV.
Discussion
In this study, we have developed and validated an easy-to-use varices risk scoring system for screening HRV in HBV-related cACLD. This novel algorithm simply included ALB, PLT and PVD, which is easy to apply in daily clinical work. The APP score avoided 51.3–56.6% EGDs for screening HRV with a < 5% HRV miss rate. Moreover, the APP score can save more EGDs than the previously reported models based on routine laboratory tests.
To create an easy-to-use model for screening HRV, the routine laboratory tests and ultrasound results were included. ALB, PLT and PVD were independent risk factors for the presence of HRV. The APP score was established based on multivariate logistic regression analysis. ALB as an independent risk variable for the presence of varices has been reported by Imran et al. [
14] and Bressler et al. [
15]. Li et al. [
16] reported that ALB with liver volume could be a potential predictor for the presence of esophageal varices. These results indicate that ALB could be a potential variable for predicting HRV. PLT as a crucial variable combined with LSM by TE has been recommended by the Baveno VI consensus to screen HRV [
7]. Chen et al. [
17] and Dong et al. [
18] reported that PLT was one of the predictors that identified patients who did not need EGDs screening. PLT combined with the length of the spleen safely ruling out HRV also has been confirmed [
19]. The portal hypertension is the driver of developing varices. The diameter of the portal vein was increased with development of portal hypertension [
20]. These results suggest that the APP score could be a potential model for screening HRV.
To assess the ability of the APP score to screen HRV, previously reported criteria based on routine laboratory tests were validated in this study, Calvaruso et al. found that ALB < 36 g/l and PLT < 120 × 10
9/l can avoid > 30% EGDs for HRV screening, which was similar with expanded the Baveno VI criteria in which LSM < 25 kPa and PLT > 110 × 10
9/l in patients with HCV-related cirrhosis [
11]. Jangouk et al. reported that PLT > 150 × 10
9/l or MELD = 6 can saves 30–54% EGDs for screening HRV in patients with cACLD [
12]. Tosetti et al. validated that PLT > 150 × 10
9/l or MELD = 6 can avoid 39% EGDs for screening varices needing treatment in patients with HBV-related cACLD [
21]. Data for these models were available in daily clinical work. In our study, these criteria avoided 31.7% and 27.6% EGDs for screening HRV, respectively. The APP score saved more EGDs than these criteria and had a similar HRV miss rate and low-risk varices miss rate to them. These results suggest that an APP score < 0.24 can save more EGD screening without increasing the risk of HRV missing in patients with HBV-related cACLD. Chronic HBV infection was a main cause of cirrhosis. PLT was significantly lower in patients with chronic HBV or HCV infection than in those with other etiologies of liver disease among patients with HRV [
22]. An APP score < 0.24 shows great potential for screening HRV in patients with HBV-related cACLD. However, whether the APP score is useful in other etiologies, especially autoimmune liver disease, should be studied in further research.
The Baveno VI criteria LSM < 20 kPa and PLT > 150 × 10
9/l are the most widely acceptable noninvasive model for screening HRV [
7]. Several large sample studies validated that the Baveno VI criteria can avoid 15–35% EGDs in patients with cACLD [
19,
23,
24]. Although the Baveno VI criteria are the most widely used model for screening HRV, which avoids a relatively low number of EGDs, the expanded Baveno VI criteria LSM < 25 kPa and PLT > 110 × 10
9/l have been established to save more EGDs, and can save more EGDs (30–50%) [
24], but it was not safe with a > 5% of VNT miss rate in some of the conditions [
23,
25]. In this study, the APP score saved > 50% EGDs. Due to the lack of TE data, there is no comparison between the APP score and LSM-based criteria for sparing EGDs.
There were several limitations that should be considered. First, this was a retrospective and single-center study, and the ultrasound and EGD examination were done by several operators in daily clinical work. There could be some bias among operators, especially in ultrasound examination. Second, the APP score was built within HBV-related cACLD; whether this score works for other etiologies was not discussed in this work. A prospective multicenter study with larger cohorts is needed to further validate this model. Third, we did not compare the APP score with the Baveno VI criteria, spleen stiffness or PSR because of the lack of LSM measured by TE or longitudinal spleen diameter. Finally, because the patients were predominantly Child-Turcotte-Pugh A, this model probably performs differently in non-Child-Turcotte-Pugh A patients.
In conclusion, we have developed and validated a score system that can avoid > 50% HRV with a low risk of HRV missing in patients with HBV-related cACLD. The APP score is established based on routine laboratory tests and ultrasound examination, which verify that it can be applied in daily clinical work. More studies are needed to validate whether the APP score is useful in other etiologies, especially autoimmune liver disease.
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