Blood Ammonia level : Is it a Clue for the Presence of Oesophageal Varices in Cirrhotic Patients ?

Background and study aim: Endoscopic screening of all patients with liver cirrhosis add major burden to endoscopic units. Non-invasive detection of Oesophageal varices (OV) help to reduce the necessity of endoscopic screening.The aim of this work is to assess the diagnostic utility of blood ammonia level (BAL) as noninvasive predictor for presence of OV and evaluate its correlation with variceal size in cirrhotic patients. Patients and Methods: This prospective cross sectional study was conducted upon 100 cirrhotic patients who attended Hepatology, Gastroenterology and Infectious diseases department, Benha University Hospital. Fasting blood ammonia was measured and upper gastrointestinal endoscopy was done for all patients. Patients were divided according to presence of OV into two groups: Group I : included 30 patients with liver cirrhosis without OV. Group II: included 70 patients with liver cirrhosis with OV who were subdivided into four subgroups: Group IIa:included 11 patients with grade I O.V. Group IIb: included 21 patients with grade II O.V. Group IIc: included 15 patients with grade III O.V. Group IId: included 23 patients with grade IV O.V. Results: The study showed that there was a highly significant increase in the mean values of BAL in cirrhotic patients with varices in comparison to those without varices. Also the study showed highly significant increase in the mean values of BAL in patients with large OV (grade III,IV) in comparison to patients with small and medium sized varices (grade I,II). By multivariate analysis, the presence of O.V. was independently associated with increased blood ammonia levels. Conclusion: Blood ammonia level could be a non invasive predictor for the presence of OV and could be clinically useful, as it correlated with the size of OV.


INTRODUCTION
Liver cirrhosis is a leading cause of death worldwide.It is the end result of a long-lasting process, usually clinically silent and unnoticed by the patient and the physician for years [1].The clinical course of patients with advanced cirrhosis is often complicated by a number of important sequelae that can occur regardless of the underlying cause of the liver disease.These include portal hypertension and its consequences of gastroesophageal variceal hemorrhage [2].Portal hypertension is a progressive, inevitable sequelae of liver cirrhosis that leads to formation of portosystemic collateral veins, among them, oesophageal varices (OV) have the greatest clinical influence because their rupture results in variceal bleeding that can be fatal.OV can be diagnosed by Upper gastrointestinal (GI) endoscopy which is the gold standard and it is recommended by guidelines to screen all cirrhotic patients for OV at the time of diagnosis.Lack of detection of OV at the first endoscopic evaluation mandates repeat endoscopy annually in decompensated cirrhotic patients and every 2-3 years in patients with compensated cirrhosis [3].
However, the majority of cases undergoing screening endoscopy either do not have varices or have varices but do not require prophylactic therapy [4].Patients without varices develop them at a rate of 8% per year and the progression from small to large varices occurs in 10 to 20% of cases yearly [5] Therefore, the identification of non endoscopic, non invasive methods that can accurately predict OV in cirrhotic patients, particularly those of large size, can help to identify patients at greatest risk and hence reduce the exigency of endoscopic screening [6].In cirrhosis, the major portion of ammonia carried by portal blood is shunted by portosystemic collaterals into systemic circulation.This raised blood ammonia level (BAL), on the other hand, could be a good mirror of portosystemic collaterals as well as portal hypertension [7].The aim of this study was to evaluate the utility of blood amonia as a non invasive predictor of OV in cirrhotic patients regarding their presence and size and compared it with platelet count/ splenic diameter ratio that is one of the most important non invasive predictors of O.V.

Study design
This cross-sectional study was carried out prospectively at the department of Hepatology, Gastroenterology and Infectious diseases, Benha University Hospital.The study was approved by ethical committee of Benha Faculty of Medicine and its University Hospitals.Before enrolling in the study, informed consent was obtained from each participant.

DISCUSSION
Oesophageal varices (OV) are the most important and critical portosystemic shunts that develop secondary to portal hypertension.Endoscopic prophylactic band ligation and nonselective beta blockers can minimize the risk of oesophageal bleeding by 50% [10].Endoscopic screening of all cirrhotic patients would lead to a large number of unnecessary endoscopies and additional burden to endoscopic units [11].The development of non-invasive methods for OV prediction could reduce the use of upper gastrointestinal endoscopy in variceal screening and also provide an alternative way to confirm the results of conventional endoscopic diagnosis [12].A total of 100 adult cirrhotic patients were selected from those attending the department of Hepatology, Gastroenterology and Infectious diseases, Benha University Hospital during the period from January to June 2015.Regarding BAL, the current study showed significant difference between cirrhotic group with OV and that without OV (p = 0.000).The mean ammonia level in cirrhotics with OV was 54.84 µmol/l while it was 39.17 µmol/l in those without OV.In addition, BAL was also significantly high in patients with large sized varices (grade III and IV).These results came in agreement with the studies done by

CONCLUSION
Blood ammonia level could be a non invasive predictor for the presence of OV and could be clinically useful, as it correlated with the size of OV.

Table ( 3
) : Diagnostic performance of platelet count / splenic diameter ratio and blood ammonia level for diagnosis of oesophageal varices.

Table ( 4
): Diagnostic performance of platelet count / splenic diameter ratio and blood ammonia level for diagnosis of large oesophageal varices (grade III and IV).
Figure (5): ROC curve of blood ammonia level for diagnosis of large oesophageal varicesTable (5):Comparison between blood ammonia level and platelet count/ splenic diameter ratio as predictors for varices Ammonia

&platelet count splenic diameter ratio Difference between areas Standard error 95% Confidence interval Significance level
[20]ificant positive correlation was noted in our study between BAL and size of varices (r=.557 and P value <0.001) according to Spearman correlation analysis.This finding was comparable with that reported by Tarantino et al.[7]where r= 0.43 and P value was <0.001.On the same hand Hassan,et al.[18]reprted that among non-invasive parameters including BAL, PVD, SVD and SLD, only BAL positively correlated with the size of OV and Khondaker et al.[13]observed moderate but significant correlation between BAL and size of OV. when comparing the performance of blood ammonia with the PLT/SLD ratio in the current work, no significant difference was detected (p value= 0.280).A result that came in agreement with Tarantino et al.[7]who do not found dissimilar reliability between BAL and PLT/SLD in prediction of OV.Although the Plts/SLD ratio do not suffer from external confounding factors but its disadvantages are consistent with changes in platalet count either in the form of thrombocytemia that is sometime related to the auto-antibodies presence which turns out in falsely low count of PLTs.or falsely high count of PLTs, as in patients suffering from liver cirrhosis with hepatocelular carcinoma[20].