Non-invasive diagnosis of liver fibrosis in children with chronic hepatitis B by transient elastography

  • Sayma Rahman Munmun Department of Pediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University , Dhaka, Bangladesh
  • Mohammad Rukunuzzaman Department of Pediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka
  • Mohammad Wahiduzzaman Mazumder Department of Pediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka
  • Archana Shrestha Yadav
  • Luthfun Nahar
  • Mohammad Benzamin Department of Pediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka
  • Abu Sayed Mohammad Bazlul Karim Department of Pediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka
Keywords: hepatitis B; liver fibrosis; transient elastography; serum ALT

Abstract

Background Chronic hepatitis B (CHB) is one of the most alarming global health problems. Children with CHB mostly remain asymptomatic but serious sequelae like cirrhosis and hepatocellular carcinoma may develop at any age. Liver biopsy, despite being the gold standard,  is not preferable for the diagnosis of liver fibrosis because it is invasive and painful. Transient elastography, a noninvasive marker for fibrosis, could play an important role in this disease.

Objective To observe the role of transient elastography in the assessment of the progression  of liver damage  in children with chronic hepatitis B.

Methods This cross-sectional study was conducted at The Department of Paediatric Gastroenterology and Nutrition of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Based on the inclusion and exclusion criteria, there were a total of 55 cases of CHB. Besides proper clinical history, physical examination, and initial investigation, transient elastography was performed in all of the cases. Liver biopsy was taken in 20 patients with raised serum ALT level after taking proper consent. Elastographic findings were compared with clinical, biochemical, virological, and histological findings.

Results The mean age was 11.46  (SD 3.6) years and 68.7% were male. Most (65.4%) of the patients were asymptomatic at presentation and biochemically normal. Liver stiffness measurements had positive but insignificant correlation with liver biopsy (r=0.43, P=0.06). Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy for transient elastography were 80%, 53.3%, 36.3%, 88%, and 60% respectively. Areas under the  ROC curve were 0.76 (95%CI 0.47 to 1.0) for patients with significant fibrosis (F? 2). Using a cut off value of 8.05 kPa, patients with significant fibrosis were detected with a sensitivity, specificity of 80% and 53%, respectively.

Findings of transient elastography were significantly associated with clinical findings like anaemia, jaundice, hepatosplenomegaly, stigmata of CLD and biochemical findings like  serum ALT, AST as well as  virological parameters.

Conclusion  Transient elastography has a limited role in confirming a diagnosis of significant fibrosis. But because of good sensitivity, transient elastography can be used as an initial presumptive diagnostic tool for assessing significant hepatic fibrosis.  A cut off value of less than 8.05 in transient elastography can be used for exclusion of significant fibrosis.

References

1. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. A ASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83. DOI: https://doi.org/ 10.1002/hep.28156.
2. McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med. 2001;135:759-68. DOI: https://doi.org/10.7326/0003-4819-135-9-200111060-00006.
3. Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39. DOI: https://doi.org/10.1002/hep.21513.
4. Hudacko R, Theise N. Liver biopsies in chronic viral hepatitis: beyond grading and staging. Arch Pathol Lab Med. 2011;135:1320-8. DOI: https://doi.org/10.5858/arpa.2011-0021-RA.
5. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;4:495-500. DOI: https://doi.org/10.1056/NEJM200102153440706
6. Colloredo G, Guido M, Sonzogni A, Leandro G. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol. 2003;39:239-44 DOI: https://doi.org/10.1016/S0168-8278(03)00191-0
7. Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995. [cited 2020 January 26]. Role of fibroscan and APRI in detection of liver fibrosis: a systematic review and meta-analysis. 2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK153989/
8. Kirk GD, Astemborski J, Mehta SH, Spoler C, Fisher C, Allen D, et al. Assessment of liver fibrosis by transient elastography in persons with hepatitis C virus infection or HIV–hepatitis C virus coinfection. Clin Infect Dis. 2009;48:963-72. DOI: https://doi.org/10.1086/597350.
9. Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29:1705-13. DOI: https://doi.org/10.1016/j.ultrasmedbio.2003.07.001
10. Foucher J, Chanteloup E, Vergniol J, Castera L, Le Bail B, Adhoute X, et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut. 2006 ;55:403-8.DOI: https://doi.org/10.1136/gut.2005.069153.
11. Hyeon CK, Chung MN, Sun HJ, Kwang HH, Oh DK, Suh I. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ. 2004;328(7446):983. DOI: https://doi.org/10.1136/bmj.38050.593634.63.
12. Chang HM, Hepatitis B virus infection. In: Suchi JF, Sokol JR, Balistreri FW, editors. Liver Disease in Children. 4th ed. New York: Cambridge University Press; 2014. p.276-90.
13. Sokal EM, Paganelli M, Wirth S, Socha P, Vajro P, Lacaille F, et al. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Hepatol. 2013;59:814-29. DOI: https://doi.org/10.1016/j.jhep.2013.05.016
14. The French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology. 1994;20:15-20. DOI: https://doi.org/10.1002/hep.1840200104
15. Roulot D, Czernichow S, Le Clésiau H, Costes JL, Vergnaud AC, Beaugrand M. Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome. J Hepatol. 2008;48:606-13. DOI: https://doi.org/10.1016/j.jhep.2007.11.020
16. Colombo S, Belloli L, Zaccanelli M, Badia E, Jamoletti C, Buonocore M, et al. Normal liver stiffness and its determinants in healthy blood donors. Digestive and Liver Disease. 2011;43:231-6. DOI: https://doi.org/10.1016/j.dld.2010.07.008
17. Rukunuzzaman M, Afroza A. Risk factors of hepatitis B virus infection in children. Mymensingh Med J. 2011;20:700-8. PMID: 22081192
18. Abdel-Hady M, Kelly D. Chronic hepatitis B in children and adolescents: epidemiology and management. Pediatric Drugs. 2013;15:311-7. DOI: https://doi.org/10.1007/s40272-013-0010-z
19. Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol. 1995;13:29-60. DOI: https://doi.org/10.1146/annurev.iy.13.040195.000333
20. Karim ASMB, Akhter S, Nazir MFH. A study of clinical profile of chronic liver diseases in children. Dhaka Shishu (Children) Hospital Journal. 1999. 15: 16-19
21. Qi X, An M, Wu T, Jiang D, Peng M, Wang W, et al.; on behalf of The CHESS Study Group. Transient elastography for significant liver fibrosis and cirrhosis in chronic hepatitis B: a meta-analysis. Can J Gastroenterol Hepatol. 2018;2018: 3406789. DOI: https://doi.org/10.1155/2018/3406789.
22. Myers RP, Elkashab M, Ma M, Crotty P, Pomier-Layrargues G. Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study. Can J Gastroenterol. 2010;24:661-70. DOI: https://doi.org/10.1155/2010/153986
23. Ekelund S. ROC curves—What are they and how are they used?. Point of Care. 2012 Mar 1;11:16-21. DOI: https://doi.org/10.1097/POC.0b013e318246a642
24. Huang R, Jiang N, Yang R, Geng X, Lin J, Xu G, et al. Fibroscan improves the diagnosis sensitivity of liver fibrosis in patients with chronic hepatitis B. Expe Thr Med . 2016;11:1673-7. DOI: https://doi.org/10.3892/etm.2016.3135
25. Arena U, Vizzutti F, Corti G, Ambu S, Stasi C, Bresci S, et al. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology. 2008;47:380-4.DOI: https://doi.org/10.1002/hep.22007
26. Fraquelli M, Rigamonti C, Casazza G, Conte D, Donato MF, Ronchi G, et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut. 2007;56:968-73.DOI: https://doi.org/10.1136/gut.2006.111302
27. Coco B, Oliveri F, Maina AM, Ciccorossi P, Sacco RO, Colombatto P, et al. Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat. 2007;14:360-9. DOI: https://doi.org/10.1111/j.1365-2893.2006.00811.x
28. Millonig G, Reimann FM, Friedrich S, Fonouni H, Mehrabi A, Büchler MW, et al. Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology. 2008;48:1718-23. DOI: https://doi.org/10.1002/hep.22577
29. Millonig G, Friedrich S, Adolf S, Fonouni H, Golriz M, Mehrabi A, et al. Liver stiffness is directly influenced by central venous pressure. J Hepatology. 2010;52:206-10 DOI: https://doi.org/10.1016/j.jhep.2009.11.018
30. Sagir A, Erhardt A, Schmitt M, Häussinger D. Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology. 2008;47:592-5. DOI: https://doi.org/10.1002/hep.22056
31. Fung J, Lai CL, Fong DY, Yuen JC, Wong DK, Yuen MF. Correlation of liver biochemistry with liver stiffness in chronic hepatitis B and development of a predictive model for liver fibrosis. Liver Int. 2008;28:1408-16. DOI: https://doi.org/10.1111/j.1478-3231.2008.01784.x.
Published
2023-08-14
How to Cite
1.
Munmun SR, Rukunuzzaman M, Mazumder M, Yadav AS, Nahar L, Benzamin M, Karim ASM. Non-invasive diagnosis of liver fibrosis in children with chronic hepatitis B by transient elastography. PI [Internet]. 14Aug.2023 [cited 22May2024];63(4):274-1. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/3039
Section
Pediatric Gastrohepatology
Received 2022-05-09
Accepted 2023-08-14
Published 2023-08-14