THE PREDICTIVE POWER BETWEEN IL28B GENE VARIANTS (RS12979860 AND RS8099917) AND THE RESPONSE OF HEPATITIS C VIRUS IN PATIENTS ON SOFOSBUVIR AND DACLATASVIR.
Main Article Content
Keywords
IL28B polymorphisms, HCV resistance, SOF + DCV therapy, ALT and PCR viral load
Abstract
Background: Hepatitis C virus (HCV) is a serious global health hazard with an estimated 71 million individuals chronically infected. Out of them, 20% may afterward develop liver cirrhosis, and 5% of the individuals with liver cirrhosis will develop hepatocellular carcinoma. IL-28B, along with IL28A and 29, represents a cluster located on chromosome 19. IL-28B stores the information needed to encode interferon lambda 3 (INF-λ3). INF-λ3 along with INF-λ1 and INF-λ2 are type 3 interferons and play a vital role in viral infections.
Objective: To identify polymorphisms occurring in IL28B genes rs12979860 and rs8099917 in patients resistant to combination therapy (SOF + DCV) and patients responding to (SOF+DCV).
Methodology: In the study, twelve diagnosed hepatitis C genotype 3 patients were taken. They were divided into two groups. Each group had six patients. One group was the treatment responder group. These patients were diagnosed as HCV patients, but their treatment had not started at the time of sampling. The other group of patients was the treatment-resistant group. These patients did not respond to two direct antiviral agents, i.e., Sofosbuvir and Daclatasvir, after 12 weeks and did not achieve a good end-treatment response. From each patient, 5cc of blood was derived and stored in an EDTA tube for IL28B analysis and a gel tube for cDNA synthesis. Samples were stored at -80C for Polymerase chain reaction and Sanger Sequencing,
Results: Among the 12 patients, rs12979860 was not detected, while rs8099917 (c.252 T > G) was observed in 7 patients, and rs8113007 (c.190 A > T) in 9 patients by chance. ALT and PCR viral load levels significantly decreased from baseline to the 84th day, indicating biochemical improvement in all patients. TG genotype of rs8099917 was more dominant then genotype TT in resistant group, and in rs8113007 genotype AT was more dominant in resistant patients as compared to genotype AA.
Conclusion: There was no significant association between genotypes and the treatment outcome, based on the change in ALT levels and the PCR viral loads both before and post-treatment. The polymorphisms studied does not have a strong effect on the outcome or treatment failure in the considered population.
References
2. Khan MU, Mahmoud MI, Butt AA. Hepatitis c virus and chronic kidney disease. Expert Review of Gastroenterology & Hepatology. 2020;14(7):579-90.
3. Lim AG, Walker JG, Mafirakureva N, Khalid GG, Qureshi H, Mahmood H, et al. Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis. The Lancet Global Health. 2020;8(3):e440-e50.
4. Ali M, Farhat SM, Saeed RF, Amraiz D, Mehmood S, Akbar S. Climate beast: a potential threat for repercussions of disease status in Pakistan. Reviews on Environmental Health. 2021;36(2):177-83.
5. Micu SI, Musat M, Dumitru A, Paduraru DN, Rogoveanu A, Dumitriu A, et al. Hepatitis C virus: host, environmental and viral factors promoting spontaneous clearance. Journal of Mind and Medical Sciences. 2020;7(2):156-61.
6. Alamri BA. Association of Interleukin IL-28 Genetic Variations in Saudi Patients Infected With Hepatitis C Virus Genotype 4: Alfaisal University (Saudi Arabia); 2023.
7. Mertowska P, Smolak K, Mertowski S, Grywalska E. Immunomodulatory role of interferons in viral and bacterial infections. International journal of molecular sciences. 2023;24(12):10115.
8. Zaki SM, Ahmed HS, Yousif MM, Awad EM. Interleukin 28B polymorphism as a predictor of sustained virological response to sofosbuvir-based therapy for hepatitis C Virus Patients. Tropical Medicine and Infectious Disease. 2022;7(9):230.
9. Fedorchenko SV, Klimenko A, Martynovich T, Liashok O, Yanchenko V. IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus. The Turkish Journal of Gastroenterology. 2019;30(5):436.
10. Khan AJ, Saraswat VA, Ranjan P, Parmar D, Negi TS, Mohindra S. Polymorphism in interferon λ3/interleukin‐28B gene and risk to noncirrhotic chronic hepatitis C genotype 3 virus infection and its effect on the response to combined daclatasvir and sofosbuvir therapy. Journal of medical virology. 2019;91(4):659-67.
11. Sugiyama M, Tanaka Y, Wakita T, Nakanishi M, Mizokami M. Genetic variation of the IL-28B promoter affecting gene expression. PloS one. 2011;6(10):e26620.
12. Aziz H, Gill U, Raza A, Gill ML. Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients. European journal of gastroenterology & hepatology. 2014;26(5):538-43.
13. Maqsood Q, Hussain M, Sumrin A. Host versus Virus: The Genetics in HCV Infection Leading to Treatment. Hepatitis C-Recent Advances: IntechOpen; 2023.
14. Salum GM, Dawood RM, Abd el-Meguid M, Ibrahim NE, Aziz AOA, El Awady MK. Correlation between IL28B/TLR4 genetic variants and HCC development with/without DAAs treatment in chronic HCV patients. Genes & Diseases. 2020;7(3):392-400.
15. Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol: chloroform. Cold Spring Harbor Protocols. 2006;2006(1):pdb. prot4455.
16. Stroffolini T, Stroffolini G. Prevalence and modes of transmission of hepatitis C virus infection: a historical worldwide review. Viruses. 2024;16(7):1115.
17. Shahriar S, Araf Y, Ahmad R, Kattel P, Sah GS, Rahaman TI, et al. Insights into the coinfections of human immunodeficiency virus-hepatitis B virus, human immunodeficiency virus-hepatitis C virus, and hepatitis B virus-hepatitis C virus: Prevalence, risk factors, pathogenesis, diagnosis, and treatment. Frontiers in microbiology. 2022;12:780887.
18. Junaid K, Rasool H, ul Mustafa A, Ejaz H, Alsrhani A, Yasmeen H, et al. Association of IL28 B and IL10 polymorphism with HCV infection and direct antiviral treatment. Annals of Clinical & Laboratory Science. 2021;51(4):512-20.
19. Khairy R. The relation between interleukin 28B gene polymorphisms (rs8099917 and rs12980275) and the response of treatment of Hepatitis C Virus genotype 4 patients to Sofosbuvir and Daclatasvir therapy. Microbes and Infectious Diseases. 2021;2(2):271-9.
20. Echeverría N, Chiodi D, López P, Sanchez Ciceron A, Angulo J, López-Lastra M, et al. IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients. Virology journal. 2018;15:1-10.
21. Machicote AP, Flichmann D, Arana E, Paz S, Fainboim H, Fainboim L, et al. IL28B SNPs rs12979860 and rs8099917 are associated with inflammatory response in Argentine chronic HCV patients. 2018.
22. ÇAKAL B, ÇAVUŞ B, Atasoy A, Altunok D, PODA M, Bulakci M, et al. IL28B rs12979860 and rs8099917 polymorphisms in patients with chronic hepatitis C and non-viral liver disease. ANNALS OF CLINICAL AND ANALYTICAL MEDICINE. 2022;13(10).
23. Tipu I, Marriage F, Platt H, Athar MA, Day PJ, Short A. The IFN-λ genetic polymorphism association with the viral clearance induced by hepatitis c virus treatment in Pakistani patients. Hepatitis monthly. 2014;14(3).
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Dr. Mohsina Haq
MBBS, MPhil (Microbiology), PhD Scholar (Microbiology), Professor of Microbiology, Pathology department, Peshawar Medical College, Peshawar, Pakistan
Dr. Jawad Ahmed
MBBS, FCPS, PhD (Microbiology), Professor of Microbiology, Khyber Medical University, Peshawar, Pakistan
Dr. Ihsan Ullah
MBBS, PhD (Immunology) Associate Professor, IPDM, Khyber Medical University, Peshawar, Pakistan
Dr Hala Rajab
MPhil, PhD (Biotechnology), Assistant Professor Peshawar Medical College, Peshawar, Pakistan
Dr. Sami Siraj
MPhil, PhD(Pharmacology), Associate Professor and Director Institute of Pharmaceutical Sciences, Khyber Medical University, Peshawar
Dr. Najeeb ul Haq
MBBS, MCPS, MRCP, FCPS(Medicine), Professor of Medicine, Peshawar Medical College, Peshawar, Pakistan
Dr. Abbas Saleem Khan
BDS, MPhil, PhD (Oral Pathology), Professor and Head of Department Oral Pathology, Peshawar Dental College, Peshawar, Pakistan