|Year : 2020 | Volume
| Issue : 1 | Page : 52-59
Assessment of renal artery resistive index as a predictor of esophageal varices and its bleeding risk in post-hepatitic cirrhosis
Samy Zaki1, Waleed M Mousa1, Abdullah H Ahmed2
1 Department of Tropical Medicine, Al-Azhar Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Radiology, Al-Azhar Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||16-Jun-2019|
|Date of Decision||17-Dec-2019|
|Date of Acceptance||26-Dec-2019|
|Date of Web Publication||26-Mar-2020|
Waleed M Mousa
Embaba, Giza 0020, 12611
Source of Support: None, Conflict of Interest: None
Background Bleeding from rupture esophageal varices (EV) is a major and life-threatening complication of liver cirrhosis (LC). Early detection of EV and prediction of its bleeding risk is important.
Objective To assess and evaluate the resistive index (RI) of the renal artery (RA) by Doppler in various stages of portal hypertensive manifestations of LC, and their values for detection of EV and its bleeding.
Patients and methods The study included 90 patients, comprising 75 patients with confirmed diagnosis of LC, classified into the following groups: group 1 included 25 patients with EV and having history of variceal bleeding episodes, group 2 included 25 patients with EV and having no variceal bleeding episodes history, and group 3 included 25 patients without EV; in addition, 15 noncirrhotic controls were included as group 4. All patients were subjected to history taking, clinical examination, laboratory investigations, calculation of some important noninvasive indices (CHILD, FIB 4, and APRI) in cirrhotic groups, abdominal ultrasonography, renal Doppler, and upper gastrointestinal endoscopy.
Results RA RI served as a predictor of the presence as well as bleeding risk of EV. LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 90% and a specificity of 76% to predict EV. Moreover, LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 92% and a specificity of 40% to predict EV bleeding. RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 80% and a specificity of 76% to predict EV. In addition, RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 88% and a specificity of 52% to predict EV bleeding.
Conclusion RI of the RA may help in predictions of EV and its bleeding risk. LRA RI was more sensitive for prediction of EV bleeding.
Keywords: esophageal varices, liver cirrhosis, resistive index
|How to cite this article:|
Zaki S, Mousa WM, Ahmed AH. Assessment of renal artery resistive index as a predictor of esophageal varices and its bleeding risk in post-hepatitic cirrhosis. Al-Azhar Assiut Med J 2020;18:52-9
|How to cite this URL:|
Zaki S, Mousa WM, Ahmed AH. Assessment of renal artery resistive index as a predictor of esophageal varices and its bleeding risk in post-hepatitic cirrhosis. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Jul 10];18:52-9. Available from: http://www.azmj.eg.net/text.asp?2020/18/1/52/281357
| Introduction|| |
It is estimated that one-third of cirrhotic patients and esophageal varices (EV) will bleed from those varices during their lifetime . The main complication of portal hypertension (PH) is bleeding from ruptured EV, which is considered a major cause of death in patients with cirrhosis . Therefore, some form of intervention to prevent the first bleeding episodes and thereby reduce mortality seems to be logically accepted. Therefore, for patients with compensated liver cirrhosis (LC), the diagnosis and grading of clinically significant PH enable prediction of prognosis . Thus, the precise grading of PH is essential for appropriate prophylactic management and follow-up of patients with hepatic cirrhosis . The current consensus is that all cirrhotic patients should be screened by upper gastrointestinal tract (GIT) endoscope for presence of varices at the time of diagnosis . Unfortunately, sedation of cirrhotic patients to perform upper endoscope may be hazardous, and diagnostic upper endoscopy may contribute to bacterial infections owing to disruption of the normal barriers . Considerable efforts have been made to identify hemodynamic indicators of the risk for variceal bleeding, noninvasively, by Doppler ultrasound (US) to reduce the increasing burden placed on endoscopy units . Although noninvasive US seems to be a reliable surrogate for hepatic venous pressure gradient for identifying PH, the correlation between US and PH remains poorly defined . The basic factor in the natural history of EV is increased portal pressure, which for cirrhosis is caused by a combination of increased hepatic vascular resistance and increased portal collateral blood flow. Therefore, increased portal pressure and the volume of blood flow are likely to be the most important factors associated with EV bleeding . The resistive index (RI) of the renal artery (RA) (RIR) indicates a worsened hemodynamic status, resulting in increased collateral blood flow. So evaluation of RIR noninvasively by Doppler study may act as an indicator of portal pressure and hyperdynamic circulation. Byun and Kim  studied 33 alcoholic cirrhotic patients and found that a high RI of the RA will be useful in predicting EV bleeding in patients with alcoholic cirrhosis. So in the current, we aimed to evaluate the RA RI as a predictor of EV in LC and its bleeding risk.
| Patients and methods|| |
The study was conducted at Tropical Medicine Department in cooperation with Radiology Department, Faculty of Medicine, Al-Azhar University hospitals, from August 2017 to February 2018. The hospital ethics committee approved the study, and informed consents were obtained from all patients who participated in the study. Of 90 patients, 75 patients had LC and 15 were noncirrhotic. The patients with LC were classified according to the result of the upper GIT endoscopy and according to EV presence and variceal bleeding episodes into the following:
- Group 1: patients with EV having variceal bleeding episodes (bleeder group) (N=25).
- Group 2: patients with EV with no variceal bleeding episodes (nonbleeder group) (N=25).
- Group 3: patients with no EV on upper GIT endoscope (N=25).
- Group 4: patients without LC (N=15).
Patients with LC were diagnosed by clinical, laboratory, and US methods. APRI (AST to Platelet Ratio Index) was also calculated . Patients having sonographic evidence of hepatic focal lesion(s), having either partial or complete portal vein thrombosis, having splenic or hepatic vein thrombosis (Budd–Chiari syndrome), having evidence of lower esophageal masses, and having any disease other than LC that may affect RI of the RA such as acute or chronic kidney disease were excluded from this study. All patients provided informed written consent.
All patients were subjected to the following:
- History taking.
- Clinical examination.
- Laboratory evaluation.
- Child–Pugh score classification.
- Abdominal US and Doppler studies were done using Philips Affiniti 70 G Machine Convex (ATL HDI 5000; Philips Healthcare, Best, The Netherlands), with probe frequency of 3.5–5 MHz. All patients were subjected to a single viewer operator; it evaluated liver and spleen size, the presence of cirrhosis, periportal fibrosis, ascites, or focal lesions and portal vein diameter.
- Doppler study of the RA.
- The RIR is the most frequently used parameter to assess intrarenal resistance and is calculated based on intrarenal duplex Doppler US measurements, as follows:
- RA peak systolic velocity (RA-PSV).
- RA minimal end diastolic velocity (RA-EDV).
- RA mean velocity (RA-MnV).
- RA RI=RA-PSV−RA-EDV/RA-PSV.
- The RIR was done for all patient using US Doppler machine, applying the aforementioned equation, which is built in the machine.
- Upper GIT endoscopy was done using a flexible video gastroscope (GIF-HQ190; Olympus Medical Systems, Shinjuku, Tokyo, Japan and Pentax EG-1840 Medical Systems, Tokyo Japan).
- EV: these were graded according to Thakeb et al.  which was based on the modification of the classification of Dagradi et al. .
- Gastric varices were graded according to the classification of Sarin et al. .
- PH gastropathy was classified according to Primignani et al. .
The current protocol was approved by the committee of Tropical Medicine Department and committee of Faculty of Medicine, Al-Azhar University, in accordance with Helsinki protocol of 2013.
All patients who were included in the current study signed an approved consent form for participation, approved by the Al-Azhar University ethical committee.
Statistical testing was performed using IBM SPSS statistics software (version 23) belong to IBM corporation situated in Armonk, New York, USA. The reported results’ significance level was set at P value less than 0.05. Data were presented (in tables) either as mean±SD and range or the number of cases (percentage of the total count of the respective group) [n (%)] in case of continuous and categorical variables, respectively. Analysis of variance with post-hoc (Tukey) test was used for comparing means, and the c2 test − with Yates correction as necessary − or Fisher’s exact test was used for comparing proportions. Multivariate analysis was done to test relation between EV as dependent variables and other factors using step-wise regression test. A receiver operating characteristic (ROC) curve was constructed using the level of renal artery (RA) RI (0.70) as cutoff points of prediction of EV and using the level of RA RI (0.70) as cutoff points of prediction of EV bleeding risk. Sensitivity, specificity, positive predictive value, negative predictive value, and test accuracy were calculated.
| Results|| |
A total of 90 patients were included in the study conducted at Tropical Medicine Department, in cooperation with Radiology Department, Faculty of Medicine, Al-Azhar University Hospitals, from August 2017 to May 2018. Of them, 75 had cirrhosis and 15 were noncirrhotic and comprised the control group. Mean age was 51.9±8.1 years, and there were 41 males and 49 females. Demographics, laboratory characteristics, and US findings among the four groups showed significant difference with age, serum albumin, platelet count, splenic diameter (mm), portal vein diameter (mm), and ascites ([Table 1]).
|Table 1 Comparative analysis of demographics, laboratory characteristics, scores, and ultrasonographic findings among the studied groups|
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Regarding Doppler study finding among four groups, it showed significant difference among the four groups regarding RA RI [right renal artery (RRA) and LRA], showing rise in RA RI in cirrhotic groups (1, 2, and 3) than control group. Moreover, RA RI values increased in group 1 (bleeder) than group 2 and group 3 ([Table 2]).
To develop a model for detection of EV, group 1 (EV bleeder group) and group 2 (EV nonbleeder group) were analyzed as a single group versus group 3 (no EV group), and showed significant difference in splenic size (cm) and portal vein diameter (mm) between the two groups, and no significant difference in ascites and Child score ([Table 3]).
|Table 3 Baseline ultrasonographic findings differentiating groups 1+2 from group 3|
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Another table for Doppler finding between groups 1+2 (EV patients) and group 3 (non-EV patients) showed significant difference in RA RI (RRA and LRA) ([Table 4]).
|Table 4 Doppler findings of study patients differentiating groups 1+2 from group 3|
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All variables that were found to have significant changes in the univariate analysis were included as candidate variables in forward logistic regression analysis to identify independent predictors for the presence of EV. In this analysis, LRA RI was found to have independent predictive values for the presence of EV. ROC curve analysis of the LT RA RI revealed that a cut off value of 0.70 has a sensitivity of 90% and a specificity of 76% for prediction of EV ([Figure 1]).
|Figure 1 ROC curve of the LRA RI for esophageal varices detection. RI, resistive index; ROC, receiver operating characteristic.|
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Moreover, ROC curve analysis of the RT RA RI revealed that a cutoff value of 0.70 had a sensitivity of 80% and a specificity of 76% for prediction of EV ([Figure 2]).
|Figure 2 ROC curve of the RRA RI for esophageal varices detection. RI, resistive index; ROC, receiver operating characteristic.|
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Another model was developed for the prediction of the presence of bleeder EV. Therefore, group 2 and group 3 were analyzed as a single group versus group 1 to develop a model for detection of EV bleeding ([Table 5],[Table 6],[Table 7],[Table 8],[Table 9]).
|Table 5 Receiver operating characteristic curve values of the LRA resistive index for esophageal varices detection|
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|Table 6 Receiver operating characteristic curve values of the RRA resistive index for esophageal varices detection|
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|Table 7 Doppler findings of study patients differentiating group 1 from group 2+3|
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|Table 8 Receiver operating characteristic curve values of the LRA resistive index for esophageal varices bleeding|
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|Table 9 Receiver operating characteristic curve values of the RRA resistive index for esophageal varices bleeding|
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All variables that were found to have significant changes in the univariate analysis were included as candidate variables in step-wise logistic regression analysis to identify independent predictors for the presence of bleeder EV. In this analysis, LT RA RI was found to have independent predictive value for the presence of bleeder EV.
ROC curve analysis of LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 92% and a specificity of 40% for prediction of EV bleeding, which means that for a given patient if the value is more than 0.70, the patient should be investigated (upper endoscope) for large possibility of having bleeder EV ([Figure 3]).
|Figure 3 ROC curve of the LRA RI for esophageal varices bleeding. RI, resistive index; ROC, receiver operating characteristic.|
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ROC curve analysis of RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 88% and a specificity of 52% for prediction of EV bleeding, which means that for a given patient if the value is more than 0.70, the patient should be investigated for large possibility of having bleeding EV ([Figure 4] and [Figure 5]).
|Figure 4 ROC curve of the RRA RI for esophageal varices bleeding. RI, resistive index; ROC, receiver operating characteristic.|
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|Figure 5 A 49-year-old male with cirrhosis. The patient had a history of hematemesis with esophageal bleeding. Doppler US shows LRA RI (a) and RRA RI (b). In this case, the LRA RI and RRA RI values were 0.73 and 0.77, respectively. RI, resistive index; US, ultrasound.|
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| Discussion|| |
EV are the most relevant portosystemic collaterals, and variceal bleeding still carries higher rates of morbidity, mortality, and hospital costs, Therefore, the American Association for the Study of Liver Diseases and the Baveno IV Consensus recommend screening by endoscope for all patients with LC for the presence of varices at the time of diagnosis .
However, endoscopy has low compliance and high cost, as the endoscopic procedure is invasive and may be not or poorly accepted by the patients if repeatedly required in a generalized endoscopic screening program in cirrhotic patients . Moreover, sedation of cirrhotic patients to perform upper endoscope may be hazardous, and diagnostic upper endoscope may contribute to bacterial infections owing to disruption of the normal barriers . For these reasons, the appropriate selection of patients who may be at risk of having EV, especially those at risk for rupture, would be highly beneficial and cost-effective . The need for noninvasive diagnosis for detection of EV and assessing the effect of therapy will benefit in high-risk situations .
Many studies have attempted to identify characteristics that predict the presence of EV noninvasively. These studies have shown that clinical, biochemical, and US parameters alone or together have good predictive power for assessing the presence of EV noninvasively .
Shastri et al.  used portal vein Doppler as a tool for noninvasive prediction of EV in cirrhosis and showed portal vein velocity had the highest sensitivity of 84% (95% confidence interval, 66.45–94.10%) for detecting the presence of EV. Portal vein diameter and hepatic congestion index had the highest specificity of 55% (95% confidence interval, 0.31–0.77). Therefore, portal vein Doppler as a predictive tool for presence of EV has several limitations, and esophago-gastro-duodenoscopy (EGD) remaining the gold standard method for the diagnosis and management of EV.
PH and increased portal venous inflow were found to be the two main factors associated with EV bleeding. The former is associated with RI of spleen, whereas the latter is associated with RIR secondary to a reduction in effective volume, which results in a hyperdynamic circulation. Increased portal venous inflow (which is equivalent to the sum of portal and collateral blood flow) is not only an important contributor to the maintenance and worsening of portal pressure elevation but also to hyperdynamic circulation. The most favored theory considers that renal vasoconstriction is the consequence of underfilling the systemic arterial circulation secondary to marked vasodilatation of the splanchnic circulation . As increased portal venous inflow is associated with hyperdynamic circulation, increased RIR may be the indirect indicator of a hyperdynamic circulation when there is splanchnic arterial vasodilatation in cirrhosis. So, a high RIR may also be associated with variceal bleeding, by means of it indicates a worsened hemodynamic status. Progressive dilatation of EV appears to be a chronic homeostatic response to a chronic increase in portal pressure and blood flow. The formation and dilatation of varices appears to relieve portal pressure and may provide a channel for replenishing a reduced effective volume. Under stable conditions, the risk for variceal rupture seems to be relatively low, as EV are the direct result of a chronic adaptive course in LC. However, any disorder that results in a rapid increase in portal flow above baseline may increase the risk of variceal bleeding. Therefore, a high RIR, representing a hyperdynamic circulation, may be significant in predicting bleeding in patients with a high basal portal pressure. The significance of this hemodynamic factor is supported by findings that bacterial infection is a significant prognostic indicator of a failure to control bleeding, as sepsis is associated with a hyperdynamic circulation .
In our study, we used RA RI for prediction of EV and their bleeding in 75 LC patients from a total 90 studied patients, and their diagnostic ability for EV was assessed using multiple statistical approaches.
Some single parameters were found to offer sufficient predictive value for EV.
The present study showed that the RI of the RA has significant importance in predicting the presence and bleeding risk of EV in cirrhotic patients.
Our study revealed that the RI of the RA was an important noninvasive predictor of EV. LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 90% and a specificity of 76% for prediction of EV. Moreover, LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 92%, and a specificity of 40% for prediction of bleeding from EV. RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 80%, and a specificity of 76% for prediction of EV. Moreover, RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 88%, and a specificity of 52% for prediction of EV bleeding.This was in line with Byun and Kim  who found a significant role of RI of the RA in predicting EV bleeding, with the mean values of variables were higher in bleeder than in nonbleeder patients. RIR had a sensitivity of 88.3%, a specificity of 75.0%, and an accuracy of 81.8% at a cutoff value of 0.70 for the prediction of bleeding.
Moreover, our finding was concordant with Thayumanavan et al.  who found high RA RI correlated directly with the degree of the varices, and a higher RA RI is associated with increased upper GI bleed. Approximately 76% (75.60%) of patients having RA RI of more than or equal to 0.67 had grades 2 and 3 varices. Approximately 66.7% having RA RI less than 0.67 had grade 1 or no varices (P<0.05). Overall, 60% of patients with RA RI more than or equal to 0.67 had an upper GI bleeding episode, and 20% of patients with RA RI <0.67 had upper GI bleeding.
In addition, our results agreed with Colli et al.  who found that the renal RI was uniformly better than the portal congestive index in detection of presence of EV in Child A LC in terms of sensitivity (58 vs. 48%), specificity (84 vs. 54%), and positive (3.60 vs. 1.04) and negative (0.50 vs. 0.96) likelihood ratios.
| Conclusion|| |
A high RA RI appeared to be associated with EV and related bleeding in patients with LC. We suggest that RA RI is a useful tool in prediction of EV and associated bleeding risk, and that it should be used clinically to decide the patients who should receive prophylactic therapy and for follow-up.
Using RA RI, either independently or through a predictive model, needs further validation.
Future studies should recruit a larger number of patients, which subsequently help create a single model that can categorize patients into either bleeding, not, or no varices at all.
Follow-up of RA RI in patients who underwent sclerotherapy or band ligation can confirm the strong correlation with the presence as well as the grade of EV, with an outcome that may obviate the need for follow-up endoscopy.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]