Evaluation of Liver Fibrosis by FibroScan in β-Thalassemia Children Infected with Hepatitis C Virus Before and After Ledipasvir/Sofosbuvir Therapy

Main Article Content

Aya Lotfy Yosef
Hanan Hamed Soliman
Gamal El-Sayed Shiha
Mohiee El-Deen AbdEl-Aziz Awad
Eslam El-Sayed El-Hawary


Background: Thalassemic children develop liver fibrosis because of liver iron overload and hepatitis C virus (HCV) infection. Transient elastography (FibroScan) can be a reliable non-invasive method for evaluating liver fibrosis in thalassemic patients. Treatment with ledipasvir/sofosbuvir (LED/SOF) direct acting antiviral agents can significantly affect liver stiffness measurement (LSM) by FibroScan.

Aims: To assess liver fibrosis by non-invasive FibroScan through LSM before and after generic LED/SOF therapy in multi-transfused β-thalassemic children infected with HCV.

Place and Duration of Study: Pediatric Hematology Unit, Tanta University Hospital, from November 2017 to May 2019.

Methodology: Fifty multi-transfused β-thalassemic treatment-naϊve children (aged 12-18 years and weighing ≥35kg) with chronic HCV infection were subjected to clinical evaluation, quantitative HCV PCR assay, FibroScan examination, and calculation of APRI, FIB4 index and AST/ ALT ratio. In addition to standard therapy, generic LED/SOF (90/400 mg) treatment was given for 12 weeks’ duration with follow up for further 12 weeks after end of treatment.

Results: A positive HCV PCR was changed into negative for all studied patients starting from week 4 after treatment. There was highly significant reduction in the LSM values by FibroScan in the studied patients after therapy (p-value <0.001) with median reduction of 19.4 %. The significant reduction in LSM values was particularly prominent in patients with significant (F2) and advanced (F3) liver fibrosis stages as well as cirrhotic patients (F4). There was significant reduction in the values of other non-invasive liver fibrosis markers FIB-4 index, APRI score and AST/ ALT ratio (p-value <0.001, <0.001 and 0.020 respectively) after therapy.

Conclusion: Generic LED/SOF therapy for 12 weeks’ duration resulted in eradication of HCV infection that was associated with significant decrease in LSM by FibroScan particularly those with higher baseline liver fibrosis stages.

FibroScan, liver fibrosis, liver stiffness measurement, β-Thalassemia, Hepatitis C virus, direct acting antiviral drugs, ledipasvir/sofosbuvir

Article Details

How to Cite
Yosef, A. L., Soliman, H. H., Shiha, G. E.-S., Awad, M. E.-D. A.-A., & El-Hawary, E. E.-S. (2020). Evaluation of Liver Fibrosis by FibroScan in β-Thalassemia Children Infected with Hepatitis C Virus Before and After Ledipasvir/Sofosbuvir Therapy. International Blood Research & Reviews, 11(3), 9-17. https://doi.org/10.9734/ibrr/2020/v11i330130
Original Research Article


Mohammad II, Al-Doski FS. Assessment of liver functions in thalassaemia. TJOPS. 2012;8(1):87-95.

Youssef S, El Alfy M, Osman A, Khattab A, El Feky M, Hussein M. Rapid detection of multiple β-globin gene mutations by a real-time polymerase chain reaction in β-thalassemia carriers. Egypt J Haematol. 2012;37(3):147-55.

Di Marco V, Capra M, Gagliardotto F, Borsellino Z, Cabibi D, Barbariae F, et al. Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C. Haematologica. 2008;93(8):1243-6.

Elalfy MS, Esma GT, Matter RM, Abdel Aziz HE, Massoud WA. Liver fibrosis in young Egyptian beta-thalassemia major patients: relation to hepatitis C virus and compliance with chelation. Ann Hepatol. 2013;12(1):54-61.

Manning DS, Afdhal NH. Diagnosis and quantitation of fibrosis. Gastroenterology. 2008;134(6):1670-81.

Xu H, Fang J, Huang S, Li H, Zhong F, Guo X, et al. Diagnostic values of serum levels of HA, PC III, C IV and LN to the liver fibrosis in children with beta-thalassemia major. Chinese J Pediatrics. 2003;41(8):603-6.

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(3):403-8.

de Lédinghen V, Douvin C, Kettaneh A, Ziol M, Roulot D, Marcellin P, et al. Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. J. Acquir. Immune Defic. Syndr. 2006;41(2):175-9.

Di Marco V, Bronte F, Cabibi D, Calvaruso V, Alaimo G, Borsellino Z, et al. Noninvasive assessment of liver fibrosis in thalassemia major patients by transient elastography (TE)–lack of interference by iron deposition. Br. J. Haematol. 2010;148(3):476-9.

Sandrin L, Fourquet B, Hasquenoph J-M, Yonv S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29(12):1705-13.

Castéra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128(2):343-50.

Tsochatzis E,Gurusamy K, Ntaoula S, Cholongitas E, Davidson BR, Burroughs AK. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol. 2011;54(4):650-9.

Saad EA. Non-invasive assessment of liver fibrosis using serum markers. J Pharm Chem Biol Sci. 2014;2(2):59-76.

Yilmaz Y, Yona Ol, Kurt R, Bayrak M, Aktas B, Ozdogan O. Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease: APRI in chronic liver disease. Hepat Mon. 2011;11(2):103-6.

Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-25.

Aziz S. Treatment of hepatitis C virus infection in children less than 12 years of age in developing countries. JCTH. 2014;2(4):247-52.

Suzuki M, Tajiri H, Tanaka Y, Takano T, Miyoshi Y, Murakami J, et al. Peginterferon therapy in children with chronic hepatitis C: a nationwide, multicenter study in Japan, 2004–2013. J Pediatr Gastr Nutr. 2016;63(1):88-93.

Yang CHT,Yoo ER, Ahmed A. The role of direct-acting antivirals in the treatment of children with chronic hepatitis C. JCTH. 2017;5(1):59-66.

Perales C, Quer J, Gregori J, Esteban J, Domingo E. Resistance of hepatitis C virus to inhibitors: complexity and clinical implications. Viruses.2015;7(11):5746-66.

Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, Buti M, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect. Dis. 2016;16(6):685-97.

AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2018;67(10):1477-92.

FDA New Release. FDA approves two hepatitis C drugs for pediatric patients. 2017. Retrieved July 29,2017. Available:https://www.fda.gov/news-events/press-announcements/fda-approves-two-hepatitis-c-drugs-pediatric-patients

Tada T, Kumada T, Toyoda H, Mizuno K, Sone Y, Kataoka S, et al. Improvement of liver stiffness in patients with hepatitis C virus infection who received direct‐acting antiviral therapy and achieved sustained virological response. J Gastroen Hepatol. 2017;32(12):1982-8.

Balistreri WF, Murray KF, Rosenthal P, Bansal S, Lin CH, Kersey K, et al. The safety and effectiveness of ledipasvir− sofosbuvir in adolescents 12‐17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2017;66(2):371-8.

Yakoot M, El-Shabrawi MH, AbdElgawad MM, Mahfouz AA, Helmy S, Abdo AM, et al. Dual sofosbuvir/daclatasvir therapy in adolescent patients with chronic hepatitis C infection. J Pediatr Gastr Nutr. 2018;67(1):86-9.

Nagral A, Jhaveri A, Sawant S, Parikh NS, Nagral N, Merchant R, et al. Treatment of chronic hepatitis C infection with direct acting antivirals in adolescents with Thalassemia Major. Indian J Pediatr. 2019;86(2):148-53.

El‐Shabrawi M, Kamal N, El‐Khayat H, Kamal E, AbdElgawad M, Yakoot M, et al. A pilot single arm observational study of sofosbuvir/ledipasvir (200+ 45 mg) in 6‐to 12‐year old children. Aliment Pharm Ther. 2018;47(12):1699-704.

Bachofner JA, Valli PV, Kröger A, Bergamin I, Künzler P, Baserga A, et al. Direct antiviral agent Treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis‐4 score and aspartate aminotransferase‐platelet ratio index. Liver Int. 2017;37(3):369-76.

Elsharkawy A, Alem SA, Fouad R, El Raziky M, El Akel W, Mahmoud Abdo, et al. Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon. J Gastroen Hepatol. 2017;32(9):1624-30.

Mohammed MA, Omar NM. Assessment of liver fibrosis after direct-acting antiviral therapy in compensated and decompensated HCV-related liver diseases. Int J Inn Res Med Sci. 2019;4(04):256-63.

Singh S, Facciorusso A, Loomba R, Falck-Ytter Y. Magnitude and kinetics of decrease in liver stiffness after antiviral therapy in patients with chronic hepatitis C: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16(1):27-38.

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(2):380-4.