32.2.24 Positive Predictive Value of Shear Wave Elastography in Predicting the Stage of Liver Fibrosis Taking Histopathology as Gold Standard

Original Article

 

SWE in  Predicting the Stage of Liver Fibrosis

Positive Predictive Value of Shear Wave Elastography in Predicting the Stage of Liver Fibrosis Taking Histopathology as Gold Standard

Rabia Asif, Amber Goraya and Abid Ali Qureshi

ABSTRACT

Objective: The objective of this study was to determine the positive predictive value of shear wave elastography (SWE) in predicting the stage 3 of liver fibrosis taking histopathology as gold standard.

Study Design: A cross-sectional study.

Place and Duration of Study: This study was conducted at the Research was conducted at Department of Diagnostic Radiology, Children Hospital Lahore, from April, 2019 to October, 2019.

Materials and Methods: This study involved 117 children of both genders aged between 1 to 15 years having chronic liver disease. Ultrasound abdomen was performed and stage 3 fibrosis was diagnosed on shear wave elastography (7.1-12.0 kPa). The diagnosis was later confirmed on histopathology of liver tissue. Diagnosis of histopathology was taken as gold standard and results of SWE on ultrasound were judged accordingly as true positive or false positive.

Results: The mean age of the children was 8.4±4.4 years while the mean weight was 32.1±14.9 Kg. There were 74 (63.2%) male and 43 (36.8%) female children. Histopathology confirmed diagnosis of Stage-3 liver fibrosis in 107 (91.5%) cases. Taking histopathological diagnosis of stage-3 liver fibrosis as gold standard, there were 107 (91.5%) true positive and 10 (8.5%) false positive cases. It yielded a positive predictive value of 91.5% for SWE on ultrasound in predicting stage 3 of liver fibrosis taking histopathology as gold standard. Similar positive predictive value was noted across various subgroups of children based on age (p-value=0.998), gender (p-value=0.824) and weight (p-value=0.969).

Conclusion: The positive predictive value of shear wave elastography on ultrasound was found to be 91.5% in predicting stage 3 hepatic fibrosis taking histopathology of liver tissue as gold standard.

Key Words: Hepatic Fibrosis, Ultrasound, Shear Wave Elastography, Positive Predictive Value

Citation of article: Asif R, Goraya A, Qureshi AA. Positive Predictive Value of Shear Wave
Elastography in Predicting the Stage of Liver Fibrosis Taking Histopathology as Gold Standard.
Med Forum
2021;32(2):98-101.

 

 

INTRODUCTION

Liver fibrosis is considered to be a complex fibrogenic and inflammatory process resulting due to chronic liver injury and is known to represent initial steps in development of liver cirrhosis. Liver cirrhosis is an important health issue globally.1,2Known etiologies of liver cirrhosis vary geographically as alcoholism, chronic hepatitis C as well as nonalcoholic fatty lives

 

 

Department of Paediatric Radiology, The Children’s Hospital & Institute of Child Health, Lahore.

 

 

Correspondence: Dr. Amber Goraya, Assistant Professor, Department of Paediatric Radiology, The Children’s Hospital & Institute of Child Health, Lahore.

Contact No: 03324161904

Email: amber.goraya@yahoo.com

 

 

Received:  August, 2020

Accepted:  October, 2020

Printed:      February, 2021

 

 

 

 

 

 

disease (NAFLD) are the most frequent in developed western part of the world while chronic hepatitis B is the most common cause in Asia-Pacific Region.3,4 Ultrasound-guided liver biopsy is considered to be the “gold standard” for diagnosing liver cirrhosis. However, ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI) are being used to stage the fibrosis of the liver by non-incisive methods.5 Guibal et al. in 2016 conducted a study on the patients suffering with liver diseases and found that the shear wave elastography (SWE) has positive predictive value (PPV) of 91.7% in predicting stage 3 fibrosis.6

There is no such local clinical study present on this topic to the best of our knowledge up to date. The SWE not only can lead to early detection of the fibrosis of the liver but also stages the fibrosis which corresponds with histopathology. As the PPV varies with the prevalence of disease there is a need to conduct this study in local population so that the PPV of SWE in determining the stage of fibrosis and progression of disease and this will ultimately help the clinicians to opt the management plane which reduces the progression of disease and to stop or delay reaching the cirrhosis and to reverse the fibrosis if the disease is treatable. The objective of this study was to determine the positive predictive value of shear wave elastography (SWE) in predicting the stage 3 of liver fibrosis taking histopathology as gold standard.

MATERIALS AND METHODS

This cross sectional study was done at Department of Diagnostic Radiology, Children Hospital Lahore, from 11/04/2019 to 10/10/2019. Approval from “Institutional Ethical Committee” was taken for this study. Informed consent was sought from parents or guardians of all study participants. A sample size of 117 cases was calculated by 95% confidence level and 5% margin of error while taking expected PPV of SWE as 91.7%.6

Inclusion criteria was patients of both sex groups with ages in the range of 1-15 years having stage-3 liver fibrosis on SWE. Patients with abnormal liver enzymes (ALT or AST >40IU) for more than 8 weeks as per clinical record undergoing SWE in the range of 7.1-12.0 kPa were labeled to have stage-3 fibrosis. All patients who had Hepatitis B or C on ELISA were excluded. Patients with congenital heart defects were also excluded. Patients who had abnormal peripheral smear as per clinical record were also not included. Patients with bleeding disorder (INR >1.5), ascites on ultrasound and histologically proven liver malignancy as per clinical record were also not included in this study.

After approval from ethical review committee of the hospital, 117 patients who presented in the radiology department, Children Hospital, Lahore fulfilling inclusion and exclusion criteria were enrolled. SWE was performed in the segment 5 of the liver. The right arm was placed in maximum abduction to enlarge the space between the ribs. During SWE acquisition, the patient was asked to stop breathing for 5 seconds. Real-time SWE 2D color map of the stiffness (in kPa) was frozen after a stabilization of at least 3 seconds. Under aseptic measures using 16-gauge needle, liver biopsy was taken and sent for the histopathology examination as per hospital protocol. Stage-3 fibrosis on histopathology was labeled as microscopic examination of liver showing bridging fibrosis along with architectural distortion.

All the data and information were noted into a specially made proforma. All the SWE were performed on the same machine by the same consultant of the radiology department and all the histopathologies were reported by the same consultant of the histopathology department to eliminate bias.

All the collected data was entered and analyzed through SPSS version 26.0. Numerical variables like age and body weight were presented by mean ±SD. Categorical variables like gender and histological diagnosis of stage 3 fibrosis were shown as frequency and percentage. Positive predictive value has been calculated by the following formula and is presented as frequency and percentage.

 

True positive

PPV ═ ─────────────────────── × 100

True positive + False positive

True Positive cases were patients having stage-3 liver fibrosis on SWE later found to be true on histopathology. False Positive cases were patients having stage-3 liver fibrosis on SWE later found to be false on histopathology. Data was stratified for age, gender and weight to address effect modifiers. Post-stratification, chi-square test was applied taking p-value≤0.05 as significant.

RESULTS

The age of the children ranged from 1 year to 15 years with a mean of 8.4±4.4 years. There were 74 (63.2%) male and 43 (36.8%) female children with a male to female ratio of 1.7:1. The weight of these children ranged from 8 Kg to 55 Kg with a mean of 32.1±14.9 Kg as shown in Table 1.

Table No.1: Demographic Characteristics of Cases

Characteristics

Number (%)

Age (years)

<5

35 (29.9%)

5-10

36 (30.8%)

>10

46 (39.3%)

Gender

Male

74 (63.2%)

Female

43 (36.8%)

Weight (kg)

<23

44 (37.6%)

24-39

27 (23.1%)

>40

46 (39.3%)

 

Table No.2: Detail of PPV across various subgroups of children

Characteristics

Cases Outcome

PPV

P-value

True Positive (n=107)

False Positive (n=10)

Age (years)

<5

32 (91.4%)

3 (8.6%)

91.4%

0.998

5-10

33 (91.7%)

3 (8.3%)

91.7%

>10

42 (91.3%)

4 (8.7%)

91.3%

Gender

Male

68 (91.9%)

6 (8.1%)

91.9%

0.824

Female

39 (90.7%)

4 (9.3%)

90.7%)

Weight (kg)

<23

40 (90.0%)

4 (9.1%)

90.9%

0.969

24-39

25 (92.6%)

2 (7.4%)

92.6%)

>40

42 (91.3%)

4 (8.7%)

91.3%

Histopathology confirmed diagnosis of stage-3 liver fibrosis in 107 (91.5%) cases as shown in Table 2. Taking histopathological diagnosis of stage-3 liver fibrosis as gold standard, there were 107 (91.5%) true positive and 10 (8.5%) false positive cases. It yielded a positive predictive value of 91.5% for SWE on ultrasound in predicting stage 3 of liver fibrosis taking histopathology as gold standard.

Similar PPV was noted across various subgroups of children based on age (p-value=0.998), gender (p-value=0.824) and weight (p-value=0.969) as shown in Tables 2.

DISCUSSION

Recent studies have reported high positive predictive value of SWE in the non-invasive diagnosis of sage 3 fibrosis among such patients,7-9 however, there was no such local published study which made us plan this work.

In the present study, the mean age of the children was 8.4±4.4 years. Parkash et al reported similar mean age of 8.5±2.7 years among children presenting with liver fibrosis.10 A similar mean age of 6.9±1.8 years has been reported by Hashmi et al among such children presenting at Shifa International Hospital, Islamabad11 while Tahir et al observed it to be 6.4±4.3 years at Fauji Foundation Hospital Rawalpindi.12 A comparable mean age of 10.7±2.1 years was found by Dhole et al from India.13

We noted male to female ratio of 1.7:1. Similarly, male predominance has been reported in a number of local studies where Hashmi et al observed it to be 2.2:1 at Shifa International Hospital, Islamabad11 and Anwar et al. reported it to be 2.1:1.14 Dhole et al found male predominance from India in such children with male to female ratio of 1.5:113 while Rukunuzzaman et al observed it to be 1.4:1 in Bangladesh.15

We found that SWE had positive predictive value of 91.5% in predicting stage 3 of liver fibrosis taking histopathology as gold standard. Our results are in line with those of Ferraioli et al who reported similar PPV of 91.3% for shear wave elastography in Italy16 and Guibal et al who reported it to be 91.7% in France.6 Thiele et al reported it to be 90.0% in Denmark.7 Comparable positive predictive value of 95.7% has been reported by Zeng et al in China.8 Cassinotto et al observed much lower positive predictive value of 52.6% in a French study9 while Jeong et al17 and Zhuang et al18 reported much higher PPV of 97.7% and 98.4% in South Korea and China respectively.

One of the limitations of this research was that we didnot consider the effect of this timely staging of liver fibrosis and anticipated management on the outcome of such children which would have further highlighted the role of SWE in the management planning of such cases.

 

CONCLUSION

The positive predictive value of shear wave elastography on ultrasound was found to be 91.5% in predicting stage 3 hepatic fibrosis taking histopathology of liver tissue as gold standard regardless of patient’s age, gender and weight which along with its non-invasive and radiation free nature and widespread and bedside availability advocate its preferred use in future practice so that risk stratification and anticipated management may improve the outcome of such children.

Acknowledgement: The authors are thankful to Muhammad Aamir (Research Consultant, Bahawalpur) for technical assistance in writing this manuscript.

Author’s Contribution:

Concept & Design of Study:

Rabia Asif

Drafting:

Amber Goraya

Data Analysis:

Abid Ali Qureshi

Revisiting Critically:

Rabia Asif, Amber Goraya

Final Approval of version:

Rabia Asif

Conflict of Interest: The study has no conflict of interest to declare by any author.

REFERENCES

1.     Zhang CY, Yuan WG, He P, Lei JH, Wang CX. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 2016;22(48):10512-22.

2.     Wiegand J. Berg T. The etiology, diagnosis and prevention of liver cirrhosis: part 1 of a series on liver cirrhosis. Dtsch Arztebl Int 2013;110(6):85-91.

3.     Zhou WC, Zhang QB, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol 2014; 20(23):7312–24.

4.     Pinzani M. Pathophysiology of Liver Fibrosis. Dig Dis 2015;33(4):492-7.

5.     Yeom SK, Lee CH, Cha SH, Park CM. Prediction of liver cirrhosis, using diagnostic imaging tools. World J Hepatol 2015;7(17):2069-79.

6.     Guibal A, Renosi G, Rode A, Scoazec JY, Guillaud O, Chardon L, et al. Shear wave elastography: an accurate technique to stage liver fibrosis in chronic liver diseases. Diagn Interv Radiol 2016;97(1):
91-9.

7.     Thiele M, Detlefsen S, Sevelsted Møller L, Madsen BS, Fuglsang Hansen J, Fialla AD, et al. Transient and 2-dimensional shear-wave elastography provide comparable assessment of alcoholic liver fibrosis and cirrhosis. Gastroenterol 2016; 150(1):123-33.

8.     Zeng J, Zheng J, Huang Z, Chen S, Liu J, Wu T, et al. Comparison of 2-D shear wave elastography and transient elastography for assessing liver fibrosis in chronic hepatitis B. Ultrasound Med Biol 2017;43(8):1563-70.

9.     Cassinotto C, Boursier J, de Lédinghen V, Lebigot J, Lapuyade B, Cales P, et al. Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatol 2016;63(6):1817-27.

10.            Parkash A, Cheema HA, Malik HS, Fayyaz Z. Congenital hepatic fibrosis: clinical presentation, laboratory features and management at a tertiary care hospital of Lahore. J Pak Med Assoc 2016;66(8):984-8.

11.            Hashmi SS, Bhatti AB, Malik MI, Rana A, Nasir H, Dar FS, et al. Spectrum of histopathological diagnosis in paediatric patients with liver disorders in Pakistan. J Pak Med Assoc 2017;67(2):266-9.

12.            Tahir A, Malik FR, Ahmad I, Krishin J, Akhtar P. Aetiological factors of chronic liver disease in children. J Ayub Med Coll Abbottabad 2011;23(2):12-4.

13.            Dhole SD, Kher AS, Ghildiyal RG, Tambse MP. Chronic liver diseases in children: Clinical profile and histology. J Clin Diagn Res 2015;9(7):SC04.

14.            Anwar A, Hashmi MA. Risk factors for viral hepatitis B and C infection in children. Pak Armed Forces Med J 2018;68(3):627-33.

15.            Rukunuzzaman M. Wilson's disease in Bangladeshi children: analysis of 100 cases. Pediatr Gastroenterol Hepatol Nutr 2015;18(2):121-7.

16.            Ferraioli G, Tinelli C, Dal Bello B, Zicchetti M, Filice G, Filice C. Liver Fibrosis Study Group. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study. Hepatol 2012;56(6):2125-33.

17.            Jeong JY, Kim TY, Sohn JH, Kim Y, Jeong WK, Oh YH, et al. Real time shear wave elastography in chronic liver diseases: accuracy for predicting liver fibrosis, in comparison with serum markers. World J Gastroenterol 2014;20(38):13920-9.

18.            Zhuang Y, Ding H, Zhang Y, Sun H, Xu C, Wang W. Two-dimensional shear-wave elastography performance in the noninvasive evaluation of liver fibrosis in patients with chronic hepatitis B: comparison with serum fibrosis indexes. Radiol 2017;283(3):873-82.