EFFECTIVENESS AND SAFETY OF DIRECT ACTING ANTIVIRAL AGENTS IN THALASSAEMIC PATIENTS WITH CHRONIC HEPATITIS C
Keywords:Sofosbuvir, Daclatasvir, Thalassemia, Hepatitis C
AbstractBackground: Pakistan has the highest prevalence of Β-Thalassemia major in children and Chronic Hepatitis C (HCV) infection is a common transfusion transmitted infection. After the emergence of new generations of Antiviral drugs labelled as Direct Acting Antivirals (DAAs), substantial eradication of HCV has been reported as 90–95% with fewer side effects as compared to older regimen of Peginterferon with or without Ribavirin. The main objective of this study was to assess the Rapid virological response (RVR) at 4th week, End of treatment response (ETR) at 12th week and sustained viral response (SVR) at 24th week achieved by using direct acting antiviral and to assess their safety. Methods: Retrospective descriptive study was conducted from July 2018 to July 2020 at National Institute of Child Health. All β-thalassemia major paediatric patients with HCV infection and age between 3–14 years were included. Demographic data, liver function test, HCV PCR, and response of antiviral therapy was recorded and analyzed. Safety was determined by adverse effects reported in records and efficacy was documented by clearance of HCV-RNA to see ETR and SVR. Results: Total 21 patients were treated. Mean age was 7.67±3yr and 12 (57%) were male. Mean weight was 19.3±3.2kg. RVR and ETR was achieved in all (100%) and SVR was achieved in 20/21 (95%) patients. Headache in 2(9.5%) and generalized body ache was found in 1 (4.25%) patient. Conclusion: Combined Sofosbuvir and Daclatasvir were found to be effective and safe for treating HCV in Thalassaemia Major Children.
1. Ahmed S. Thalassaemia in Pakistan. J Islamic Intl Med Coll 2018;13(2):50–1.
Ansari SH, Shamsi TS, Ashraf M, Bohray M, Farzana T, Khan MT, et al. Molecular epidemiology of β-thalassemia in Pakistan: Far reaching implications. Indian J Hum Genet 2012;18(2):193–7.
Kiani RA, Anwar M, Waheed U, Asad MJ, Abbasi S, Zaheer HA. Epidemiology of Transfusion Transmitted Infection among Patients with β-Thalassaemia Major in Pakistan. J Blood Transfus 2016;2016:8135649.
Ali MA, Arif MM, Arif A, Fatima T. Viral Hepatitis C in Thalassaemia: Determination of Antibody HCV Frequency in Mutitransfused Thalassaemia Patients. Ann Punjab Med Coll 2016;10(1):20–5.
Daher HB, Sharara AI. Treatment of Chronic HCV Infection in Patients with Thalassemia. Clin Liver Dis (Hoboken) 2020;14(6):199–202.
Waheed U, Abdella YE, Saba NE, Arshad M, Wazeer A, Farooq A, et al. Evaluation of screening effectiveness of hepatitis B surface antigen and anti-HCV rapid test kits in Pakistan. J Lab Physicians 2019;11(4):369–72.
Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J, et al. Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 2002;100(1):17–21.
Aziz S. Treatment of Hepatitis C Virus Infection in Children Less than 12 Years of Age in Developing Countries. J Clin Transl Hepatol 2014;2(4):247–52.
Vermehren J, Park JS, Jacobson IM, Zeuzem S. Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection. J Hepatol 2018;69(5):1178–87.
Mehta R, Kabrawala M, Nandwani S, Desai P, Bhayani V, Patel S, et al. Safety and Efficacy of Sofosbuvir and Daclatasvir for Hepatitis C Virus Infection in Patients with β-Thalassemia Major. J Clin Exp Hepatol 2018;8(1):3–6.
Indolfi G, Serranti D, Resti M. Direct-acting antivirals for children and adolescents with chronic hepatitis C. Lancet Child Adolesc Health 2018;2(4):298–304.
Hashmi MA, Cheema HA. Effectiveness and Safety of Sofosbuvir in Treatment-Näive Children with Hepatitis C Infection. J Coll Physicians Surg Pak 2017;27(7):423–6.
Khaliq S, Raza SM. Current Status of Direct Acting Antiviral Agents against Hepatitis C Virus Infection in Pakistan. Medicina (Kaunas) 2018;54(5):80.
Sinakos E, Kountouras D, Koskinas J, Zachou K, Karatapanis S, Triantos C, et al. Treatment of chronic hepatitis C with direct-acting antivirals in patients with β-thalassaemia major and advanced liver disease. Br J Haematol 2017;178(1):130–6.
Manisha S, Sanjeev K, Seema N, Dilip C, Rashmi D. A Cross-Sectional Study on Burden of Hepatitis C, Hepatitis B, HIV and Syphilis in Multi-Transfused Thalassemia Major Patients Reporting to a Government Hospital of Central India. Indian J Hematol Blood Transfus 2015;31(3):367–73.
Angelucci E, Pilo F. Treatment of hepatitis C in patients with thalassemia. Haematologica 2008;93(8):1121–3.
Alvi MA, Cheema HA, Saeed A, Batool S. Ribavirin free direct-acting antivirals in adolescents with hepatitis C and thalassemia. J Fatima Jinnah Med Univ 2018;12(3):110–4.
Butt N, Reema S, Ali Khan M, Abbasi A, Butt S, Khoso M M, et al. Efficacy and Safety of Sofosbuvir and Ribavirin for Treating Chronic Hepatitis C, Genotype 3: Experience of a Tertiary Care Hospital at Karachi, Pakistan. Cureus 2019;11(4):e4458.
Schwarz BK, Rosenthal P, Murray KF, Honegger JR, Hardikar W, Hague R, et al. Ledipasvir−Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old with Chronic Hepatitis C. Hepatology 2020;71:422–30.
Kamal S, Abdelhakam S, Ghoraba D, Mohsen MA, Salam AA, Hassan H, et al. The course of hepatitis C infection and response to anti-viral therapy in patients with thalassemia major and hepatitis C infection: a longitudinal, prospective study. Mediterr J Hematol Infect Dis 2019;11(1):e2019060.
Herbst Jr DA, Reddy KR. Sofosbuvir, a nucleotide polymerase inhibitor, for the treatment of chronic hepatitis C virus infection. Expert Opin Investig Drugs 2013;22(4):527–36.
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013;368(20):1878–87.
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.
Wirth S, Rosenthal P, Gonzalez‐Peralta RP, Jonas MM, Balistreri WF, Lin CH, et al. Sofosbuvir and ribavirin in adolescents 12‐17 years old with hepatitis C virus genotype 2 or 3 infection. Hepatology 2017;66(4):1102–10.
Cuypers L, Pe´rez AB, Chueca N, AldamizEchevarrı´a T, Alados JC, Martı´nez-Sapiña AM, et al. Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis. PLoS One 2018;13(7):e0201268.
Chalabi DA, Al Azzawi S. Antiviral Treatment of Chronic Hepatitis C Infection among Children and Adolescents with Beta Thalassemia Major. Med J Babylon 2019;16(4):340–5.
Padhi S, Maharshi S, Gupta GK, Garg K, Nijhawan S. Efficacy and safety of direct acting antiviral therapy for chronic hepatitis C in Thalassemic children. J Pediatr Hematol Oncol 2018;40(7):511–4.
Zamani F, Ajdarkosh H, Safarnezhad-Tameshkel F, Azarkeivan A, Keyvani H, Naserifar F, et al. The effectiveness of sofosbuvir and daclatasvir in the treatment of hepatitis C in thalassaemia major patients and their effect on haematological factors. Indian J Med Microbiol 2018;36(2):224–9.