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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 2  |  Page : 594-599

Liver stiffness measurement by fibroscan for predicting esophageal varices in patients with chronic liver diseases


1 Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Shebin El kom, Egypt
2 Tropical Medicine Department. in ShebinElkom Fever Hospital, Shebin El kom, Egypt

Date of Submission08-Nov-2016
Date of Acceptance21-Dec-2016
Date of Web Publication27-Aug-2018

Correspondence Address:
Mona M Abdelmaksoud
Shebin Elkom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.239745

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  Abstract 


Objective
The aim of the present study was to measure liver stiffness by fibroscan to predict esophageal varices (EV) in patients with chronic liver diseases.
Background
Fibroscan is a novel, noninvasive, ultrasound-based technology that allows measuring liver stiffness. It is a noninvasive method for assessing EV, developed as an alternative to endoscopy.
Patient and methods
A total of 75 patients with chronic liver diseases were included in a case–control study from January 2015 to January 2016, aged greater than 18 years, with BMI less than 30 kg/m2, no history of previous endoscopic intervention for EV, no treatment with β-adrenergic receptor blockers, and absence of hepatocellular carcinoma or ascites. Patients underwent clinical examination, laboratory investigations, abdominal ultrasonography, upper endoscopy, and fibroscan. They were divided into the following groups: group I, no varices; group IIa, small varices (grades 1 and 2), and group IIb, large varices (grades 3 and 4).
Results
The mean liver stiffness values were higher in group II (35.29 ± 10.07 kPa) compared with group I (22.80 ± 8.01 kPa), with high statistically significant differences (P < 0.001) and the best cut-off value (22.7 kPa) for the presence of varices. The sensitivity was 90%, and specificity was 56%. The mean liver stiffness values were higher in patients with large varices (group IIb) (46.50 ± 5.99 kPa) than in patients with small varices (group IIa) (31.75 ± 8.38), with high statistically significant differences (P < 0.001) and the best cut-off value (37 kPa) for the presence of large varices. The sensitivity was 91%, and specificity was 79%.
Conclusion
Liver stiffness measurement can predict the presence of EV and can also detect large-sized varices.

Keywords: chronic liver diseases, esophageal varices, fibroscan, liver stiffness


How to cite this article:
El Lehleh AM, Seleem HE, Abdelmaksoud MM. Liver stiffness measurement by fibroscan for predicting esophageal varices in patients with chronic liver diseases. Menoufia Med J 2018;31:594-9

How to cite this URL:
El Lehleh AM, Seleem HE, Abdelmaksoud MM. Liver stiffness measurement by fibroscan for predicting esophageal varices in patients with chronic liver diseases. Menoufia Med J [serial online] 2018 [cited 2018 Nov 19];31:594-9. Available from: http://www.mmj.eg.net/text.asp?2018/31/2/594/239745




  Introduction Top


Chronic liver disease (CLD) is considered as an important cause of morbidity and mortality and represents a major health burden worldwide. Liver cirrhosis is the final common pathway of many cases of CLD [1]. Development of esophageal varices (EV) is a major complication that may occur in up to 90% of cirrhotic patients [2]. Variceal bleeding is a life-threatening event that has an incidence of 5% in patients with small EV and up to 15% in those with large EV; mortality per bleeding episode is around 10–20% [3]. Most cirrhotic patients develop EV over their life time (5–15%/year), and the rate of progression from small to large varices is estimated to be 8% per year [4].

Screening endoscopy in all cirrhotic patients at the time of diagnosis and periodic endoscopy in patients with previously diagnosed EV are performed to reduce the risk of bleeding by prophylactic treatment with B-blockers or endoscopic variceal ligation [5]. However, although gastrointestinal endoscopy is the most accurate and reliable method for detecting EV, it is an invasive and uncomfortable procedure for patients [4].

There is still need for simple, reliable, noninvasive methods that would allow limiting the indications of upper tract endoscopy to a subgroup of patients especially at risk [6]. Noninvasive parameters including platelet count, spleen size, and the platelet count/spleen diameter ratio are noninvasive methods for the assessment of the development of varices as alternatives to endoscopy [7].

Liver stiffness measurement (LSM) relies on the calculation of liver stiffness from the velocity of a low-frequency elastic wave inside the liver [6].

Transient elastography is a novel, noninvasive, ultrasound-based technology that allows measuring liver stiffness. Established evidence has indicated that transient elastography had good sensitivity and specificity for fibrosis, significant fibrosis, and cirrhosis [8].

The aim of the present study was to measure liver stiffness by fibroscan to predict EV in patients with CLDs.


  Patients and Methods Top


This study included 75 patients with CLDs, and were selected from patients who visited or were admitted to Shebin Elkom Fever Hospital from January 2015 to January 2016. Twenty five of them had no EV (group I), and 50 of them had EV (group II). Group II was further subdivided into those with small varices (group IIa) (grades 1 and 2) and those with large varices (group IIb) (grades 3 and 4). Classification of EV was carried out according to the Paquet classification [9] in to the following: grade 1 – small varices flattened by insufflation of air; grade 2 – slightly larger varices that do not flatten; grade 3 – larger varices that do not touch in the middle of the lumen; and grade 4 – varices that are large and touch each other in the middle of the lumen.

Informed consent was obtained from all participants before the study. Approval from the local research ethics committee was obtained.

Patients with the following criteria were excluded from the study: age less than 18 years, BMI greater than 30 kg/m 2 as the fatty thoracic belt attenuates elastic waves making LSMs inaccurate, presence of ascites as it interferes with the elastic wave of the fibroscan, patients with previous endoscopic intervention for EV, patients on treatment with β-adrenergic receptor blockers, and patients with hepatocellular carcinoma.

All patients were subjected to full and detailed history taking; complete clinical examinations; BMI measurements; laboratory investigations such as complete blood count, liver function tests including alanine transaminase, aspartate transaminase, international normalized ratio (INR), serum albumin, and serum bilirubin, serum creatinine, and random blood glucose; abdominal ultrasonography; and upper gastrointestinal endoscopy. LSM using fibroscan was carried out, and results are expressed in kiloPascals and correspond according to the manufacturer's recommendations to a median of 10 validated measurements. The validity of the results also depends on two important parameters: (i) the interquartile range, which reflects the variability of the validated measures and should not exceed 30% of the median value and (ii) the success rate (the ratio of the number of successful measurements to the total number of acquisitions) should be at least 60%.


  Results Top


The present study was conducted on 75 patients – 25 of them with no evidence of EV by upper gastrointestinal tract endoscopy (group I), and 50 patients with evidence of EV by upper gastrointestinal tract endoscopy (group II), including 38 patients with small EV (group IIa) and 12 patients with large EV (group IIb).

In the present study, 54 (72%) patients were males and 21 (28%) were females. Their ages ranged from 28 to 60 years with a mean of 48.55. Their BMI ranged from 24.1 to 30 with a mean of 27.38. There was no statistically significant difference between both groups regarding age and sex (P = 0.05 and 1.00, respectively) [Table 1].
Table 1: Socio-demographic characters and BMI of the studied groups

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In this study, there were statistically significant differences between both groups regarding spleen and portal vein diameters (P < 0.001). The mean ± SD of spleen diameter was higher in group II than in group I (14.98 ± 1.19 vs. 12.68 ± 1.46), and the mean ± SD of portal vein diameter was higher in group II than in group I (13.42 ± 1.21 vs. 10.34 ± 1.16).

Regarding Child–Pugh score, in group I, 23 (92%) patients were Child–Pugh A and two (8%) patients were Child–Pugh B, and in group II 21 (42%) patients were Child–Pugh A and 29 (58%) patients were Child–Pugh B.

Regarding liver stiffness measured by fibroscan and its relation to Child–Pugh score, there was a statistically significant difference in mean liver stiffness values (P = 0.007) between patients with Child–Pugh A score (29.56 ± 13.48 kPa) and patients with Child–Pugh B score (43.55 ± 15.86 kPa) [Figure 1].
Figure 1: Liver stiffness in relation to Child–Pugh score in all patients.

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There were statistically significant differences regarding hemoglobin levels, platelet count, serum albumin, and INR between group I and group II, whereas there was no statistically significant difference regarding other laboratory parameters. The mean ± SD of hemoglobin was 11.77 ± 1.47 in group I vs. 10.22 ± 1.32 in group II with a P- value less than 0.001. The mean ± SD of platelets was 167.96 ± 44.15 in group I vs. 120.74 ± 35.24 in group II with a P- value less than 0.001. The mean ± SD of serum albumin was 3.75 ± 0.39 in group I vs. 3.45 ± 0.47 in group II with a P- value less than 0.001. The mean ± SD of INR was 1.09 ± 0.15 in group I vs. 1.17 ± 0.14 in group II with a P- value of 0.04 [Table 2].
Table 2: Laboratory findings of the studied groups

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Hemoglobin level, platelet count, and serum albumin were significantly lower in group IIb than in group IIa, whereas there was no statistically significant difference regarding other laboratory parameters. The mean ± SD of hemoglobin was 11.21 ± 0.99 in group IIa vs. 10.22 ± 1.42 in group IIb with a P- value of 0.03. The mean ± SD of platelet count was 128.13 ± 37.08 in group IIa vs. 97.33 ± 11.06 in group IIb with a P- value less than 0.001. The mean ± SD of serum albumin was 3.68 ± 0.42 in group IIa vs. 3.27 ± 0.49 in group IIb with a P- value 0.007 [Table 3].
Table 3: Laboratory findings of group IIa and group IIb

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The mean liver stiffness value measured by fibroscan was significantly higher in group II compared with group I (35.29 ± 10.07 vs. 22.80 ± 8.01 kPa, respectively, P < 0.001) [Table 4], and there was a high statistically significant difference in mean liver stiffness between group IIb and group IIa (46.50 ± 5.99 vs. 31.75 ± 8.38 kPa, respectively, P < 0.001) [Table 5]. The cut-off value for predicting varices was 22.7 kPa (sensitivity 90% and specificity 56%) [Table 6] and [Figure 2], and the cut-off value of liver stiffness for predicting large varices was 37 kPa (sensitivity 91% and specificity 79%) [Table 7] and [Figure 3].
Table 4: Relationship between liver stiffness values and presence of esophageal varices

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Table 5: Relationship between liver stiffness values and size of esophageal varices

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Table 6: Cut-off value of liver stiffness for predicting the presence of esophageal varices

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Figure 2: Receiver operating characteristic (ROC) curve of sensitivity, specificity, and accuracy of Fibroscan in predicting the presence of esophageal varices.

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Table 7: Cut-off value of liver stiffness for predicting the size of varices

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Figure 3: Receiver operating characteristic (ROC) curve of sensitivity, specificity, and accuracy of liver stiffness in predicting the size of esophageal varices.

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When we studied other noninvasive methods for predicting EV, we found that platelet count, spleen diameter, and the platelet count/spleen diameter ratio were significantly correlated with the presence of EV (P < 0.001). We found that the platelet count/spleen diameter ratio was lower in group II (patients with varices) than in group I (patients without varices) (885.77 ± 350 vs. 1348.16 ± 402.06), with sensitivity and specificity for the prediction of EV of 86 and 56%, respectively, positive predictive value (PPV) of 80%, negative predictive value (NPV) of 67%, and area under receiver operating characteristic (AUROC) of 80.1% at a cut-off value of 1302 [Figure 4] and with sensitivity and specificity for the prediction of large-sized EV of 83 and 63%, respectively, PPV of 42%, NPV of 92%, and AUROC of 81.7% at a cut-off value of 739 [Figure 5].
Figure 4: Receiver operating characteristic (ROC) curve of sensitivity, specificity, and accuracy of the platelet count/spleen diameter ratio in predicting the presence of esophageal varices.

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Figure 5: Receiver operating characteristic (ROC) curve of sensitivity, specificity, and accuracy of the platelet count/spleen diameter ratio in predicting the size of esophageal varices.

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  Discussion Top


The ability of fibroscan to predict the presence and size of EV was evaluated in this study, and we found that LSM was higher in patients with EV (group II) (35.29 ± 10.07 kPa) than in patients with no varices (group I) (22.80 ± 8.01 kPa), with high statistically significant differences (P < 0.001) and the best cut-off value (22.7 kPa) for the presence of varices. The sensitivity was 90%, specificity 56%, PPV 80%, NPV 74%, and AUROC 82.6%. Therefore, LSM by fibroscan has a significant role in predicting the presence of varices.

Furthermore, liver stiffness was higher in patients with large varices (group IIb) (46.50 ± 5.99 kPa) than in patients with small varices (group IIa) (31.75 ± 8.38 kPa), with high statistically significant differences (P < 0.001) and the best cut-off value (37 kPa) for presence of large varices. The sensitivity was 91%, specificity 79%, PPV 58%, NPV 82%, and AUROC 91.8%. Therefore, LSM by fibroscan has a role in differentiation between small and large-sized varices.

In agreement with these results, Kazemi et al. [10] reported that the optimal cut-off point for LSM was 13.9 kPa, with 95% sensitivity and 43% specificity, and a cut-off point of 19 kPa for the detection of large-sized EV, with 91% sensitivity and 60% specificity.

Vizzutti et al. [11] reported that LSM positively correlated with the presence of EV and determined 17.6 kPa as the cut-off value for predicting EV with a sensitivity of 90% and specificity of 43%. However, no correlation between LSMs and EV size was detected.

In addition, Bureau et al. [12] found that LSM with a cut-off point of 21 kPa can predict EV in patients with CLD, with 89.9% sensitivity and 93.2% specificity, but no correlation between the LSM and the size of EV.

A study by Eric et al. [13] found that a LSM of 48 kPa was the optimal cut-off for predicting large EV with a sensitivity of 73.2% and specificity of 73.2%.

Pritchett et al. [14] reported that liver stiffness of more than 19.8 kPa could be utilized as a cut-off for endoscopy and β-blocker utilization, particularly in patients with hepatitis C.

A study by Horia et al. [15] predicted presence of EV at a cut-off of 19 kPa with sensitivity of 84%.

Stefanescu et al. [16] reported that a LSM value higher than 28 can be used to predict the presence of EV in cirrhotic patients with 74.3% sensitivity and 64.2% specificity.

Sporea et al. [17] reported a cut-off value greater than 29.5 kPa with 77.5% sensitivity, 86.9% specificity, and 78.9% for predicting the presence of significant EV.

Sharma et al. [18] reported a cut-off value of 27.3 kPa with 91% sensitivity and 72% specificity.

Yasmin et al. [19] reported that fibroscan was a good predictor of small EV at a cut-off of 29 kPa with 95% sensitivity and 67% specificity. In addition, it was a predictor of large EV at a cut-off of 38 kPa with 100% sensitivity and 77.3% specificity.

Pár et al. [20] concluded that noninvasive LSM by fibroscan allows to predict the presence of EV in patients with CLD and may help select patients for endoscopic screening, as they found high measurement sensitivity of 85% and specificity of 87% at a cut-off of 19.2 kPa liver stiffness for the presence of EV.

Adriana et al. [21] found that a cut-off value of LSM greater than 15 kPa has a sensitivity of 95.5% and specificity reaching 100% for predicting the presence of EV and a cut-off value of LSM greater than 28.80 kPa with sensitivity of 87.2% and specificity of 82.76% for the presence of large varices.

Bogdan et al. [22] reported that presence of EV can be predicted at a cut-off value of 21.1 kPa.

Hu et al. [23] reported that liver stiffness of more than 25.5 kPa could be utilized as a cut-off for predicting EV with 84.1% sensitivity, 72.5% specificity, PPV 71.7%, NPV 90.8%, and AUROC 85.5%.


  Conclusion Top


Measurement of liver stiffness by fibroscan is reliable for predicting the presence and size of EV. Therefore, it is a good test to replace endoscopy for detecting and grading EV.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

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