Abstract
Gastroesophageal varices are the most common complication of portal hypertension and associated with a worse prognosis. Endoscopy is the gold standard method to diagnose gastroesophageal varices. However, endoscopy is an invasive method with potential complications and is not well adhered by patients. Non-invasive methods, including serum markers or scores, computed tomography, ultrasonographic, and elastography-based methods, have been explored for the diagnosis of gastroesophageal varices. In the current chapter, we will briefly review non-invasive methods for the prediction of gastroesophageal varices.
Keywords
- portal hypertension
- gastroesophageal varices
- non-invasive
- diagnosis
- prediction
1. Introduction
Portal hypertension is defined as the pressure of portal vein is 5 mmHg higher than that of inferior vena cava. It is the most important complication of liver cirrhosis. Clinically significant portal hypertension is associated with an increased risk of developing varices, which is defined as hepatic venous pressure gradient over 10 mmHg [1]. Gastroesophageal varices (GEVs) is appeared in approximately 50% of patients with cirrhosis, which is associated with a worse outcome. Despite an improvement of treatment strategy, variceal bleeding is still associated with a 6-week mortality rate of 12–26% [2, 3].
Endoscopy, the gold standard method to diagnose GEVs, is recommended for all patients at the time of diagnosis of cirrhosis. Endoscopy should be periodic for screening GEVs. It is reported that nearly 30% of cirrhotic patients screened by endoscopy found to have moderate-to-large varices [4, 5]. Endoscopy is not only a diagnostic method but also serves as a therapeutic option in the form of sclerotherapy and band ligation. However, endoscopy is an invasive method, which is not well perceived by patients. Complications following diagnostic endoscopy mainly include infection, bleeding, duodenal hematoma, bowel perforation, airway obstruction, arrhythmias, and aspiration. Additionally, in some less developed regions or countries, advanced endoscopy and experienced endoscopists are still in shortage. It is thus important to identify patients who can avoid unnecessary endoscopy or patients with high-risk GEVs that need further treatment should be considered.
Non-invasive prediction of GEVs could relieve medical, social, and economic costs. Numerous efforts have been made to predict GEVs non-invasively, and some progress has been achieved. In the Baveno VI consensus conference, it was underlined that non-invasive methods should be used to rule out patients with varices or high-risk varices [6]. In this chapter, we focus on non-invasive methods in the prediction of GEVs.
2. Serum markers or scores
2.1 Serum ammonia
Serum ammonia is well recognized as a serum marker for hepatic encephalopathy in cirrhotic patients. Studies have demonstrated serum ammonia has a positive correlation with the presence of portosystemic collateral veins including GEVs [7]. In a newly published study by
2.2 Platelet count/spleen diameter ratio
Platelet count/spleen diameter ratio (PSR) was first proposed by
Since then, extensive studies have focused on the PSR for the non-invasive prediction of GEVs. However, a study by
In a recent meta-analysis by
2.3 Liaoning score
The Liaoning score was proposed by
For external validation of Liaoning score,
2.4 Other scores
Other than the non-invasive methods we have discussed above, many scores have been developed for the evaluation of liver fibrosis, including aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, and Lok scores. Some studies explore the predictive ability of these non-invasive scores for GEVs. In a meta-analysis by
3. Image tools
3.1 CT
CT scanning is one of the most important image tools in clinical practice, is recommended for the surveillance of hepatocellular carcinoma in all cirrhotic patients. GEVs characteristics as round, tubular, or serpentine structures in the esophagus and/or gastric lumen in CT images. It provides a possibility that an experienced physician can diagnosis GEVs using CT images, especially in contrast-enhanced CT images.
In a study by
3.2 Ultrasonography
Ultrasonography is the most common, cost-effective, and convenient imaging tool in clinical practice, which can be used for screening of hepatocellular carcinoma, measure the width of the portal vein, inferior vena cava, and diameter of the spleen.
Splenoportal index was calculated as the splenic index divided by mean portal vein velocity. In a study by
3.3 Elastography-based methods
Elastography-based methods, Including transient elastography (TE), point shear wave elastography, two-dimensional shear wave elastography, and magnetic resonance elastography have been used to non-invasively detected liver fibrosis and GEVs. There is substantial evidence suggesting that TE had a good correlation with portal hypertension and varices in cirrhotic patients [19, 20]. In 2015, TE was recommended for the surveillance of GEVs by Baveno VI consensus [6]. According to the Baveno VI consensus, in patients with compensated advanced chronic liver disease, who had a liver stiffness <20 kPa measured by TE and platelet count >150,000/mm3, had a low risk of developed GEVs that may spear endoscopy.
In a study by
In a study by
4. Discussion
GEVs exists in almost 30–60% of cirrhotic patients, depending on the severity of portal hypertension [24]. The occurrence of GEVs and varices-related AUGIB significantly worsened the prognosis of patients with portal hypertension, emphasizes the importance of diagnosis and management of GEVs. There are numerous studies have focused on developing non-invasive methods to predict the presence of GEVs, including serum markers, CT scanning, and ultrasonographic parameters. However, endoscopy is still difficult to replace, especially considering cost-effectiveness and diagnostic accuracy [26]. From other perspectives, in regular physical examination or surveillance of hepatocellular carcinoma, non-invasive methods can be employed to predict the severity of portal hypertension and GEVs. In this situation, if the patients have a high-risk of variceal bleeding in a short time, then the patient must perform endoscopy; if the patient has a low-risk of bleeding in a certain period, then the patient can waive an unnecessary endoscopy.
Liver stiffness and spleen stiffness measured by the TE were the most promising non-invasive methods available, as they have proven having a good correlation with liver fibrosis, portal hypertension, and the presence with varices [27, 28]. The limitations of TE is that the results of TE should interpreted by a specialist in liver disease which may not available in less development hospital and TE should inappropriate be performed in patients with ascites and/or obesity [26].
Approximately 10% of the whole portal hypertension patients were non-cirrhotic portal hypertension [29]. In general, patients with non-cirrhotic portal hypertension have higher prevalence and larger size of varices than those in cirrhotic patients [30, 31]. Until now, few studies focus on the non-invasive prediction of GEVs in patients with non-cirrhotic portal hypertension. In a retrospective observational study by
There are heterogeneities among these studies and methods. Several reasons for the heterogeneities, including: 1) different target populations were enrolled among studies, including different races, etiology of liver cirrhosis; 2) different severity of underlying liver disease among patients; 3) different definitions for the risk of GEVs: in some studies, such as the study by
5. Conclusion
Endoscopy is still the first choice for the diagnosis of GEVs in patients with portal hypertension. Liver stiffness and spleen stiffness measured by TE are the most studied methods. With the development of non-invasive prediction of GEVs, it is promising to exempt some patients from endoscopy.
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