Variceal bleeding occurs in 20–40% of cirrhotic patients with esophageal varices and is associated with a high morbidity and mortality [2]. The Baveno IV 2005 Consensus Workshop [1, 4] have determined that every patient diagnosed with cirrhosis should be investigated for EV, regardless of Child class and the cause of liver cirrhosis [5].
Several studies have examined how to identify patients with varices using noninvasive methods to avoid large number of unnecessary screening endoscopy in patients with a low risk of varices [6]. Various portal haemodynamic indices have been shown to be predictive of the severity of EV or risks of variceal bleeding in patients with cirrhosis [14].
This prospective case control study was conducted on 2 groups: group 1, 100 cirrhotic patients which was classified into two subgroups after upper GI endoscopy; group1A, cirrhotic patients with esophageal varices and Group1B, cirrhotic patients without esophageal varices, and group 2, 100 of healthy volunteers as a control group.
As regards the demographic data of the studied cirrhotic groups, 57% of cirrhotic patients were males and 43% were females. Their ages ranged from 36 to 78 years (49.31 ± 14.27) in group 1A and (52.88 ± 14.45) in group 1B. these observations go in agreement with with Tharwa et al. [15], where males were 59.4% and Hekmatnia et al. [16], who found that, the mean age was 52.1 years (range: 28–83 years).
In our study, there was high statistical significant difference between group 1A and group 1B as regarding child classification (p value < 0.001). This was proven by [17], Nashaat et al. [18], and Zaman et al. [19], who reported that, patients in Child B or C are nearly 3 times more likely to have varices than those in Child A.
Concerning pelvi-abdominal ultrasound findings, there was high statistical significant difference between group1A and group1B regarding portal vein diameter (PVD), liver echogenecity, spleen size, and splenic collaterals (p value < 0.001). These results were in agreement with Faisal et al. [20], and Khalil et al. [21], who concluded that, increased PVD, splenomegaly and presence of splenic collaterals by ultrasound can predict EV specially the large varices. However, This result was in controversy with Berzigotti et al. [22], who found that, there was no significant change in liver echogenicity in cirrhotic patients with varices than patients without varices.
In our study, there was no significant difference in PVD (mm) in cirrhotic patients (12.4 ± 3.2) compared with the controls (12.1 ± 1.2) with (p value >0.05). However, There was high significant increase in PVD in group 1A (13.9 ± 2.2) than group 1B (9.4 ± 2.8) with (p value < 0.001) with high statistical significant increase with the grades of EV with (p value < 0.001). These results were in agreement with Anda et al. [23], Sarwar et al. [24] and Kayacetin et al. [25] who found an association between an increase in PVD with liver cirrhosis, presence and grading of EV as well. But these results were in disagreement with Jaheen et al. [26], who concluded that, PVD is not sensitive to presence of cirrhosis or in differentiation between the grades of EV presence.
In our study, at a cutoff point (10.4), the sensitivity of PVD that can predict EV was 94.03%, the specificity was 75.76%, PPV was 88.73%, NPV was 86.21%, accuracy was 88% and AUC = 0.877. These results were in agreement with Berzigotti et al. [22] and Nouh et al. [27] who found the best cut-off value of PVD for EV prediction was (10.7) and (11.5) respectively.
Regarding platelet count/spleen diameter ratio (PC/SD), there was high statistical significant difference in group 1A (546 ± 290.9) than group 1B (1135 ± 413.2) and the grades of EV (725.6 ± 273.5) (567.9 ± 280.2) (347.8 ± 162.6) (293.8 ± 91.8) in grades I, II, III and IV respectively as well (p value < 0.001). This result was in agreement with Shekar et al. [12], Agha et al. [28], and Elhady et al. [29], who who explained the decrease in PC/SD ratio by increase in spleen size and thrombocytopenia which usually occur with increase of portal pressure and with development of varices especially with larger risky varices.
Our study showed that, at cutoff point (604), the sensitivity of PC/SD ratio that can predict the presence of EV was 61.19%, the specificity was 90.91 %, PPV was 93.18%, NPV was 53.57 %, accuracy was 71.00% and AUC = 0.883. These results were in agreement with studies of Shekar et al. [12], Sheta et al. [30] and Nouh et al. [27], who reported that, at cut-off values around (600), PC/SD ratio that can predict EV with similar sensitivity, specificity , PPV & NPV.
Regarding the measured portal hemodynamic indices by Duplex Doppler ultrasound, there was high significant decrease of portal vein flow velocity (PVFV) (cm/s), in cirrhotic patients (15.3 ± 5.1) compared with controls (18.2 ± 2.9) with (p < 0.001) with high significant decrease in in group 1A (12.2 ± 2.3) than group 1B (21.4 ± 3.2) with (p value <0.001). Studies were done by Elhady et al. [29], Mahmoud et al. [31] and Liu et al., [32] reported that (PVFV) was significantly lower in cirrhotic patients than controls. Anda et al. [23] and Elbarbary et al. [33] Also, found that, PVFV was lower in patients with EV. In contrast, Schneider et al. [34] and Piscaglia et al. [35] reported that, no change in PVFV between patients and controls. This may be due to intra- and inter observer variability or presence of collaterals which affect the velocity.
Our study showed that, at cutoff point (15.2), the sensitivity of PVFV that can predict EV was 89.55%, the specificity was 93.94%, PPV was 96.77%, NPV was 81.58%, accuracy was 91.00% and AUC = 0.953. These results were in agreement with Minal et al. [36] who reported that, PVFV had a high sensitivity 84% for detecting the EV.
Regarding the portal congestion index (PCI) there was a significant increase in cirrhotic patients (0.11 ± 0.045) compared with the controls (0.071 ± 0.012) and increase in group 1A (0.1 ± 0.03) than group1B (0.05 ± 0.0.1) with (p value < 0.001). These results were in agreement with Kayacetin et al. [25] who found that, PCI was significantly increased in cirrhotic group and in presence of EV.
At cutoff point (0.1), the sensitivity of PCI that can predict EV was 89.35%, the specificity was 92.84%, PPV was 95.66%, NPV was 82.5%, accuracy was 93% and AUC = 0.948. this was in agreement with Moriyasu et al. [8], who found that, cutoff point was (0.189) in patients with EV with sensitivity (84.65%) and Lee et al. [37], who found that PCI cutoff point was (0.089).
Regarding arterial indices including HARI, HAPI and SARI, there was high significant increase in the in cirrhotic patients than the controls (p < 0.001) with SARI showed high statistically significant difference between group 1A and group 1B (p value < 0.001), These results were in agreement with Park et al. [38], Zhang et al. [9], Piscaglia et al. [35] Dewidar et al. [39] and Nicolau et al. [40] who found increase in the arterial indices in cirrhotic patients than in controls and in pateints with varices than patients without.
This study showed that, at cutoff point (0.71), the sensitivity of HARI that can predict EV was 76.12%, the specificity was 91.23%, PPV was 92.11%, NPV was 67.35%, accuracy was 84.00% and AUC = 0.881. Concerning SARI, at cutoff point (0.72), the sensitivity of SARI that can predict EV was 77.61%, the specificity was 92.56%, PPV was 93.98%, NPV was 68.75%, accuracy was 85% and AUC = 0.888. These results were in agreement with Child et al. [41] and Dib et al. [42]who found that, the presence of EV affect all measured hepatic and splenic arterial hemodynamic parameters with the best cut off point for SARI for prediction of EV was (0.76) with sensitivity of 85% and specificity of 77.5%.
This study showed that, at cutoff point(1.3), the sensitivity of HAPI that can predict EV was 94.03%, the specificity was 66.67 %, PPV was 85.14%, NPV was 84.62 %, accuracy was 85.00% and AUC = 0.858. These results were in agreement with a study of Haktanir et al. [43], who reported that, HAPI was significantly higher in EV with a cutoff point (1.28).
In this study there was no statistical significant difference between the measured portal hemodynamic indices and the grade of EV (p value > 0.05) except PC/SD ratio and PVD as fore-mentioned. These results were in agreement with a study done by Hekmatnia et al., who found that, there was no significant relationship between PCI, arterial resistance and pulsatility indices and the grades of EV [16].
In contrast, results published by Anda et al. [23], showed a significant increase in PCI, HARI and HAPI with higher grades of EV, this could be attributed to the difference in the number of selected cirrhotic patients and different degree of decompensation between these studies [23].
Regarding portal hypertensive index (PHI) there was high statistical significant increase in PHI in cirrhotic group than control group with (p value < 0.001), with high statistical significant increase in PHI in group 1A than group 1B with (p value < 0.001) . this was in agreement with Iwao et al. [44] who found that, PHI had a specificity > 70% when comparing cirrhotic patients with controls and also in agreement with Faisal et al. [20] who found that, PHI showed statistically significantly higher values in patients with EV than those without EV.
At cutoff point (1.48), the sensitivity of PHI that can predict EV was 92.43%, the specificity was 93.94 %, PPV was 97.10%, NPV was 96.45%, accuracy was 95.00% and AUC = 0.992. %. These results were in agreement with Abu El Makarem et al. [45] who found that, only PHI had an independent predictive value of EV and suggested the beginning of endoscopic screening in patients with compensated cirrhosis at a cutoff point of PHI (> 2.08).
As regards, the liver vascular index (LVI), there was no significant difference in cirrhotic patients compared with the controls (p value > 0.05), this result was in controversy with Jaheen et al. [26], who found that, LVI was significantly lower in cirrhotic patients than controls with (p value = 0.018).
There was high statistical significant decrease in LVI in group 1A than group 1B with (p value < 0.001), this result was in agreement with a study done by Faisal et al. [20], who found that, LVI was lower in patients with EV (p value=0.001).
At cutoff point (9.4), the sensitivity of LVI that can predict EV was 74.63%, the specificity was 96.97 %, PPV was 98.04%, NPV was 65.31 %, accuracy was 82.00% and AUC = 0.973. These results were in agreement with Haktanir et al. [43], who found that, the best cut off point for LVI for prediction of EV was (10.36) with sensitivity of 85% and specificity of 77% and concluded that, LVI was a high sensitive and specific parameter in the diagnosis and prediction of EV.
However, Piscaglia et al., and Jeon et al., have reported different findings in the measured portal hemodynamic indices compared with the present study results. They reported that, Doppler measurements were not useful in distinguishing patients with liver cirrhosis from healthy individuals. However, clinical tests including biochemistry and ultrasonography would be useful in selecting eligible patients for screening endoscopy [46, 47]. This could be attributed to the difference in the number of patient and control groups, the difference in etiology of liver cirrhosis in western countries, and difference in the degree of hepatic decompensation.
Additional studies are required in a larger number of cirrhotic patients of different etiologies and different grades of Child classification for validation of portal hemodynamic indices and to determine universal best cut off values that can be safely recommended as noninvasive predictors of esophageal varices.