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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 3  |  Page : 1113-1118

Right liver lobe diameter/serum albumin ratio in the prediction of esophageal varices in cirrhotic patients


1 Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Diagnostic Radiology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
3 Department of Tropical Medicine, Shibin El Kom Teaching Hospital, Shebeen El-Kom, Egypt

Date of Submission02-Mar-2019
Date of Acceptance14-Apr-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Ahmad Y. H. Metwally
Shibin El Kom 32511, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_73_19

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  Abstract 

Objective
This study aimed to assess the role of right liver lobe diameter by ultrasound/albumin ratio in the prediction of esophageal varices (OV) in cirrhotic patients.
Background
OV often develop in cirrhotic patients. Varices rupture leading to variceal bleeding represents the most lethal complication of cirrhosis. Right liver lobe diameter/albumin (RLLD/Alb) ratio is a noninvasive method to predict the presence of OV.
Patients and methods
A case–control study was carried out on 200 cirrhotic patients (145 with OV and 55 without OV). Patients were subjected to complete blood picture, liver and kidney functions, viral markers, abdominal ultrasonography, upper gastrointestinal tract endoscopy, and calculation of the RLLD/Alb ratio and the platelet count/spleen diameter (PC/SD) ratio.
Results
The RLLD/Alb ratio was diagnostic for the prediction of OV with high significance (P ≤ 0.0001). At a cut-off point of 3.7, the sensitivity, specificity, and accuracy to predict OV were 95, 76.4, and 90%, respectively, with area under the curve = 0.88. A highly statistically significant difference was also noted in the PC/SD ratio with a sensitivity, specificity, and accuracy of 83.4, 70.3, and 80.9%, respectively, at a cut-off point of 605. A statistically significant positive correlation was found between both the RLLD/Alb ratio and the PC/SD ratio and grades of OV and the risk of bleeding from varices (P = 0.0001).
Conclusion
The RLLD/Alb ratio and the PC/SD ratio are useful as noninvasive predictors of OV in cirrhotic patients.

Keywords: cirrhosis, esophageal varices, right lobe/albumin ratio


How to cite this article:
Nouh MA, El-Hamouly MS, Mohamed SA, Metwally AY. Right liver lobe diameter/serum albumin ratio in the prediction of esophageal varices in cirrhotic patients. Menoufia Med J 2019;32:1113-8

How to cite this URL:
Nouh MA, El-Hamouly MS, Mohamed SA, Metwally AY. Right liver lobe diameter/serum albumin ratio in the prediction of esophageal varices in cirrhotic patients. Menoufia Med J [serial online] 2019 [cited 2019 Nov 19];32:1113-8. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/1113/268839




  Introduction Top


The development of esophageal varices (OV) is among the major complications of liver cirrhosis, with a prevalence of 50%. Variceal bleeding occurs in 20–40% of cirrhotic patients with OV and is associated with a high morbidity and mortality, reaching about 17–57% from each episode of variceal bleeding [1].

The guidelines recommend screening liver cirrhosis patients by endoscopy to identify those at risk of bleeding so that they can administer prophylactic therapy [2]. Screening should be performed at various intervals: every 2–3 years for those with compensated cirrhosis and no varices, every 1–2 years if there are small varices, and every year for those with decompensated cirrhosis irrespective of the presence of varices [3].

As Egypt has the highest prevalence of hepatitis C virus-related hepatitis and cirrhosis (7% i.e. about 3.7 million, with a prevalence of 15% or more in the delta region) [4], very large numbers of patients require endoscopic screening for the presence of OV, Performing such large number of endoscopic examinations is very coasty and time consuming. Furthermore, patients are unlikely to be compliant with repeated endoscopy [5].

Therefore, there is a need for a noninvasive method that can predict the presence of OV. Ideally, a method for identifying patients with OV should be simple, noninvasive, inexpensive, reproducible, accurate, and readily available, has high sensitivity and specificity, follows the natural history, reflects the effect of the treatment accurately, and indicates the prognosis and possibility of success of a treatment [6].

In this study, we aimed to evaluate the role of right liver lobe diameter by the ultrasound/albumin ratio as a potential noninvasive predictor of OV in cirrhotic patients.


  Patients and Methods Top


We carried out a case–control study on 200 patients with liver cirrhosis diagnosed by physical findings, laboratory investigations, and ultrasonographic findings. One hundred and forty-five of these patients had OV, whereas the remaining 55 had no OV and were considered the control group.

We excluded all patients with hepatocellular carcinoma, primary hematologic disorders, for example, hemophilia, portal vein thrombosis, patients who underwent splenectomy, and patients on β-blockers or regular albumin infusion.

This study was approved by the Committee for Ethics of Faculty of Medicine, Menoufia University, Egypt. The study was explained to each patient, including the aim and methods of the research, and a written consent was obtained from all participants.

All studied patients were subjected to the following:

  1. Through assessment of history
  2. Detailed clinical examination including a general examination and a local examination
  3. Laboratory investigations including complete blood count, liver function test (Alanine Transferase, Aspartate Transferase, serum albumin, bilirubin total and direct, prothrombin time, International Normalization Ratio), kidney function test (serum creatinine, serum urea), and viral markers (Hepatitis C Virus Antibody, Hepatitis B surface Antigen) by ELISA.
  4. Radiology:


  5. Abdominal ultrasound was performed by a single expert radiologist who was blinded to the patient's history, clinical, and laboratory data using the high-resolution Voluson (GE Healthcare, Chicago, USA), with a focus on measurement of the right liver lobe diameter and spleen diameter (long axis in mm), assessment of portal vein for patency, measurement of the diameter, and determination of the presence and grading of ascites

  6. Endoscopy:


  7. Upper gastrointestinal endoscopy was performed for all patients by a single experienced endoscopist using the Olympus Exera II device (Olympus medical system, Tokyo, Japan).

    If OV were present, they were classified into four grades following Conn's classification (1967):

    1. I: varices visible during only one phase of respiration
    2. II: varices visible during both phases of respiration
    3. III: 3–6 mm in diameter
    4. IV: more than 6 mm in diameter


  8. Calculation of the right liver lobe diameter (cm)/serum albumin concentration (g/dl) and platelet count (PC) (mm 3)/spleen bipolar diameter (mm).


Statistical analysis

Data were analyzed statistically using statistical package for the social sciences (SPSS) (IBM, New York, New York, USA) program version 22 for Windows. The following tests were used to test differences for significance. Differences between frequencies (qualitative variables) and percentages in groups were compared using the χ2-test. Differences between parametric quantitative independent groups were determined using a t-test. For all the analyses, a P value less than 0.05 was considered statistically significant.


  Results Top


In terms of the demographic data of the patients in this study, the age ranged from 33 to 73 years, with a mean of 58.67 ± 9.03; 142 (72%) patients were men and 56 (28%) were women [Table 1].
Table 1: Presence and grading of varices among the studied population

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A highly statistically significant difference was noted between patients with different grades of OV and those without OV and patients with bleeding varices and those without bleeding in terms of Child–Pugh class, for example, the more advanced the Child class of the patient, the more advanced the grade of OV, and the higher the risk of bleeding from OV [Table 2] and [Table 3].
Table 2: Radiological parameters, right lobe diameter/albumin ratio, and platelet count/spleen ratio in different grades of varices

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Table 3: Radiological parameters, right lobe diameter/albumin ratio, and platelet count/spleen ratio in patients with and without bleeding varices

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At a cut-off value of 3.7, the sensitivity of the right liver lobe diameter/albumin (RLLD/Alb) ratio to detect OV was 95%, the specificity was 76.4%, the positive predictive value (PPV) was 91.4%, the negative predictive value (NPV) was 85.7%, and the accuracy was 90%. The area under receiver operator characteristic (ROC) curve was 0.88 [Table 4] and [Figure 1]. However, at a cut-off value of 605, the sensitivity of the platelet count/spleen diameter (PC/SD) ratio to detect OV was 83.4%, the specificity was 70.3%, the PPV was 86.5%, the NPV was 61.1%, and the accuracy was 80.9%. The area under ROC curve was 0.796 [Table 4] and [Figure 2]. The combination of the RLLD/Alb ratio with the PC/SD ratio had a sensitivity of 96.6, a specificity of 50%, and an accuracy of 83.5%, with area under the curve = 0.73 [Table 5] and [Figure 3].
Table 4: Accuracy of the right lobe diameter/albumin ratio and the platelet count/spleen ratio in the prediction of esophageal varices

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Figure 1: Right lobe diameter/albumin ratio in prediction of esophageal varices.

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Figure 2: Platelet count/spleen in prediction of esophageal varices.

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Table 5: Accuracy of the right lobe diameter/albumin ratio and the platelet count/spleen ratio in the prediction of esophageal varices

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Figure 3: Platelet count/spleen and right lobe diameter/albumin ratio in prediction of esophageal varices.

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  Discussion Top


Variceal bleeding occurs in 20–40% of cirrhotic patients with OV and has a high morbidity and mortality (about 17–57% from each episode of variceal bleeding) [7]. Hence, it is recommended that every patient diagnosed with cirrhosis should be investigated by endoscope for OV, irrespective of Child class and cause [3],[8].

Egypt has the highest prevalence of hepatitis C virus-related hepatitis and cirrhosis (7% i.e., about 3.7 million, with a prevalence of 15% or more in the delta region), Performing endoscopic screening for all patients with liver cirrhosis would be extremely coasty and time consuming [4].

Therefore, there is a need for a noninvasive method that can predict the presence of OV, which, ideally, should be simple, noninvasive, inexpensive, reproducible, accurate, and readily available; has high sensitivity and specificity; follows the natural history; reflects the effect of the treatment accurately; and indicates the prognosis and possibility of success of a treatment [5].

This study was carried out on 200 patients with liver cirrhosis to evaluate the possibility of using the RLLD/Alb ratio as a noninvasive predictor of OV in cirrhotic patients to refer screening endoscopy to those who are at high risk of having OV.

In the population studied, 72.5% of the patients had OV and 27.5% had no OV.

Cherian et al. [8] found that 77.7% of their patients had varices and 22.3% had no varices. Agha et al. [9], in their study, reported that 82% of the patients had varices and 18% had no varices.

In terms of the sonographic findings, a statistically significant difference was also noted in spleen diameter and portal vein diameter between patients with and without OV (P = 0.0001), which is also in agreement with Mostafa et al. [10] and Elhady et al. [11].

Patients with OV are noted to have a more shrunken right lobe (with a diameter of 12.85 ± 1.25) than those without OV (diameter of 14.38 ± 0.87) (P = 0.0001).

In comparison with this study, Sharma and Aggarwal [12] concluded that shrunken liver correlated significantly with the presence of varices (diameter of 10 for patients with OV VS 12 for patients without OV, P = 0.02).

Interestingly, serum albumin level was found to be significantly lower in patients with OV than those without OV (2.7 ± 0.49 for patients with OV vs. 3.93 ± 0.66 for patients without OV).

Hussain et al. [13], in a study that was carried out on 100 cirrhotic patients, concluded that hypoalbuminemia alone is a good marker for the presence of OV.

According to the Child–Pugh classification, most patients were Child C (50%), with Child A present in 33.5% of patients and Child B in 16.5%. Sharma and Aggarwal [12] and Cherian et al. [8] reported a high proportion of patients 51.4 and 53%, respectively, in Child C.

In this study, with advancing Child–Pugh class, the percentage of patients with varices increased as 17.24% of patients with OV were classified as Child class A, 22.09% as class B, and 60.67% as class C, whereas in patients without OV, 76% were class A, 1.8% were Child B, and 21.8% were class C. These results are in agreement with the results of Said et al. [10], Tafarel et al. [14], and Nashaat et al. [15].

There was a statistically significant positive correlation between the RLLD/Alb and the grade of varices as the mean RLLD/Alb ratio was 4.2 ± 0.6 for grade 1 varices, 4.7 ± 0.57 for grade 2, 4.85 ± 0.57 for grade 3, and 5.75 ± 0.41 for grade 4 (P = 0.0001).

Alempijevic et al. [16] also found that the RLLD/Alb ratio had a significant positive correlation with the grading of OV and Child score.

There was also a statistically significant positive correlation between the PC/SD ratio and grading of OV as the mean PC/SD ratio was 593.5 ± 339.6 for grade 1 varices, 538.5 ± 62.6 for grade 2, 406.2 ± 6.99 for grade 3, and 325 ± 58.8 for grade 4.

Cherian et al. [8] reported a significant positive correlation between the presence of OV, grading of OV, Child classification grades, and the PC/SD ratio.

In terms of bleeding from varices, a statistically significant difference was found between patients with bleeding varices and patients without bleeding in the INR, spleen diameter, right lobe diameter, albumin, PC (P = 0.0001), and portal vein diameter (P = 0.001).

Umar et al. [17] found that an abnormal coagulation profile (increased INR), thrombocytopenia, increased splenic diameter, and increased portal vein diameter are strong predictors of bleeding in patients with varices. However, he they did not find any correlation with albumin and right liver lobe diameter.

Mandal et al. [18] also noted that splenomegaly and portal vein diameter are reliable predictors of variceal hemorrhage.

A significant correlation was also noted between bleeding and both the RLLD/Alb ratio (mean of 74 ± 4.07 for nonbleeding vs. 79 ± 5.04 for bleeding, with P = 0.0001) and the PC/SD ratio (mean of 728.3 ± 642.9 for nonbleeding vs. 539.1 ± 622.5 for bleeding, with P = 0.0001; [Table 3]).

Umar et al. [17] found a significant correlation between bleeding and the individual components of the ratio, for example, PC/SD. However, he they did not find a correlation between the RLLD/Alb ratio and bleeding. Nevertheless, this finding can be justified by the fact that the RLLD/Alb ratio had a significant positive correlation with the size of OV and Child score as proven by Alempijevic et al. [19]. There is a higher risk for bleeding as the size of OV increases. Also, with advancing Child score, when the clotting profile becomes abnormal level; the patients are at a higher risk of bleeding as previously proven by Umar et al. [17].

The RLLD/Alb ratio was significantly higher in patients with varices (4.9 ± 0.75) compared with those without varices (3.76 ± 0.66). At a cut-off value of 3.7, the sensitivity was 95%, specificity was 76.4%, PPV was 91.4%, NPV was 85.7%, and accuracy was 90%. The area under ROC curve was 0.88.

The application of the RLLD/Alb ratio as a predictor of OV was originally proposed by Alempijevic et al. [19]. In a study of 94 cirrhotic patients, they found that the RLLD/Alb ratio correlated with the presence of OV. At a cut-off value of 4.425, the sensitivity was 83.1% and the specificity was 73.9%.

Another study, also by Alempijevic et al. [19], reported that the RLLD/Alb ratio had a significant positive correlation with the size of OV and Child score. The sensitivity and specificity of RLLD/Alb ratio were 93 and 95%, respectively, and the accuracy of the test was 96.5%, with the best cut-off point value at 4.683.

Other studies also supported these results such as Adel and George et al. [20] (sensitivity of 80% and specificity of 70% at a cut-off value of 3.5) Mostafa et al. [10] (sensitivity of 93%, specificity of 95%, and accuracy of 96.5% at a cut-off value of 4.683), and Raj et al. [16] (sensitivity of 83.3% and specificity of 29.5% at a cut-off value at 4.42).

The difference between this study and the other studies can be explained by many factors, such as different etiology of cirrhosis, for example, in the Alempijevic study, the patients had mixed etiology (alcoholic 43%, infective 19%, autoimmune 17%, others 15%), the different ethnic backgrounds of the patients in those studies in addition to the difference between the sonographers and endoscopists of different studies.

Thrombocytopenia was more prominent in patients with OV (with a mean platelet 81 530 ± 17 780) than patients without OV (mean platelet 139 420 ± 48 230).

Zaman et al. [21] concluded that PC of less than 100 000 can be used as a predictor of OV and that of less than 90 000 is associated with an increased risk of having OV by nearly 2.5-folds. Also, Thomopulos et al. [22] concluded that thrombocytopenia (PC < 118 000) and splenomegaly (>135 mm) can predict the presence of OV in cirrhotic patients.

Thrombocytopenia associated with chronic liver disease and OV is probably a reflection of the degree of portal hypertension and possibly other factors, for example, splenic sequestration or antibody-mediated destruction of platelet. However, other factors have been implicated in thrombocytopenia such as reduced hepatic production of liver-derived platelet growth factor (thrombopoietin) or direct suppressive effects of viruses on the bone marrow.

As thrombocytopenia cannot be attributed solely to portal hypertension and there are many other causes of thrombocytopenia in patients with chronic liver disease, the use of PC alone as a noninvasive predictor of OV can be misleading. The use of the PC/SD ratio ensures that thrombocytopenia is mainly because of hypersplenism secondary to portal hypertension and not due to other factors [12].

In this study, the mean PC/SD ratio was 527.05 ± 628.44 for patients with OV and 734.4 ± 632.92 for patients with no OV.

At a cut-off value of 605, the sensitivity was 83.4%, the specificity was 70.3%, the PPV was 86.5%, the NPV was 61.1%, and the accuracy was 80.9%. The area under ROC curve was 0.796.

Giannini et al. [23] were the first to introduce the use of the PC/SD ratio as a tool to predict OV. In that study, when a cut-off value of 909 was used, the sensitivity was 100% and the specificity was 93%.

Shekar et al. [22] reported a mean value of PC/SD ratio in patients without OV of 1277, whereas in patients with OV, it was 445, with cut-off less than 608, sensitivity of 80.77% and specificity of 64%. Also, Sheta et al. [24] reported a cut-off value of less than 570 with a sensitivity of 77.1%, a specificity of 93.02%, PPV of 93.6%, and NPV of 75.5%.

Giannini et al. [25] reported the results of a multicenter study to validate the use of the PC/SD ratio in the prediction of OV. At a cut-off value of 909, the sensitivity was 92% and the specificity was 67%.

The differences between the best cut-off values, sensitivity, specificity, and accuracy in this study and other studies may be attributed to several factors influencing the PC including infection, bleeding, drugs, and lower thrombopoietin levels in patients with liver cirrhosis. In addition, the absence of interobserver agreement between the sonographers and endoscopists of the different studies can affect the results[26]

On using both the RLLD/Alb ratio and the PC/SD ratio together, the sensitivity was 96.6%, specificity was 50%, and accuracy was 83.5%. The area under ROC curve was 0.73.


  Conclusion Top


The RLLD/Alb ratio, PC/SD, and Child–Pugh class can serve as good noninvasive predictors of OV. These are also linked to the risk of bleeding from varices, and can be used in combination with other factors such abnormal clotting profile (raised INR) and portal vein diameter to predict patients at high risk of bleeding.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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