Association of TNF-alpha (-308 A/G) and IFN-gamma (+874 A/T) gene polymorphisms in response to spontaneous and treatment induced viral clearance in HCV infected multitransfused thalassemic patients.

BACKGROUND: Multitransfused thalassemic individuals are at high risk of developing transfusion transmitted Hepatitis C virus (HCV) infection. The aim of the study was to correlate the effects of host cytokine single nucleotide polymorphisms of TNF-α (-308 A/G) and IFN-γ (+874 A/T) in spontaneous or IFN induced treatment response in the HCV infected thalassemic individuals. METHODS: A total of 427 HCV sero-reactive thalassemic individuals were processed for HCV viral genomic diversity and host gene polymorphisms analysis of TNF-α (-308 A/G) and IFN-γ (+874 A/T). RESULTS: Out of 427 HCV sero-reactive individuals, 69.09% were found to be HCV RNA positive with genotype 3 as the predominant infecting strain (94.29%). Study highlighted that, A allele was significantly associated with (p < .05) spontaneous clearance of HCV infection and G allele was correlated with viral persistence at TNF-α (-308) gene polymorphism. Whereas in case of IFN-γ (+874) SNPs, A allele was significantly responsible (p < .05) for spontaneous clearance than T allele. Our study also indicated that in relapsed cases, IFN-γ (+874) T allele is more responsible than A allele. Though no significant correlation was found at both TNF-α (-308) and IFN-γ (+874) gene polymorphism among SVR and relapsed thalassemic patients. CONCLUSION: A allele at both TNF-α (-308) and IFN-γ (+874) were strongly associated with spontaneous clearance among this population. But in case of SVR and relapsed cases no significant association was found. This cytokine gene polymorphisms pattern will help clinicians to take an informed decision about therapeutic management of HCV infected thalassemic individuals.

Experience of hepatitis C virus seroprevalence and its genomic diversity among transfusion-dependent thalassemia patients in a transfusion center.

INTRODUCTION: One of the most common blood-borne transfusion-transmitted diseases is hepatitis C. Patients with a history of multiple blood transfusions are significantly at a greater risk of infection by contaminated blood and blood products. Beta thalassemia major is one such condition where repeated blood transfusions are required for patient management. MATERIALS AND METHODS: The present study was conducted to investigate the serological prevalence of hepatitis C virus (HCV), its viremia, and genotype distribution with clinical parameters among multitransfused thalassemic individuals. In this study, a total of 300 patients were screened to detect anti-HCV antibody in serum, along with liver function parameters and genotyping. RESULTS: Seventy-five (25%) patients were found to be HCV positive by enzyme-linked immunosorbent assay (ELISA). Among them, 49 (65%) were HCV RNA positive having a significant viral load in their blood and rest 26 (35%) were below detection level, which signify auto clearance of the virus in those patients. According to our study, HCV genotype 3 was the major circulating strain (92.59%) followed by genotype 1. Liver enzymes, such as alanine aminotransferase, aspartate aminotransferase, and total bilirubin, were significantly elevated among HCV seroreactive individuals. CONCLUSIONS: This study clearly indicates that the incidence of transfusion-transmitted hepatitis C is high in thalassemia patients, but actual scenario of HCV viremia can only be found by HCV RNA qualitative and quantitative detection method and not by ELISA, is a major concern for this high-risk group of population.

Interferon λ3 gene (IL28B) is associated with spontaneous or treatment-induced viral clearance in hepatitis C virus-infected multitransfused patients with thalassemia.

BACKGROUND: Hepatitis C virus (HCV) is the major posttransfusion infection in multitransfused individuals in India with thalassemia major. To our knowledge, this study is the first conducted to correlate and comprehend the effects of the host interleukin (IL)28B gene polymorphism at loci rs12979860 and rs8099917 in spontaneous or interferon (IFN)-induced treatment response in the HCV-seroreactive individuals with thalassemia major. STUDY DESIGN AND METHODS: A total of 557 HCV-seroreactive individuals with thalassemia were processed for HCV viral genotyping and host IL28B single-nucleotide polymorphism analysis at loci rs12979860 and rs8099917. RESULTS: Of 557 individuals, 70.92% were found to be HCV RNA positive with Genotype 3 (95.18%) as predominant strain. A favorable CC allele at locus rs2979860 and TT allele at rs8099917 were 75.31 and 77.16%, respectively, which was strongly associated with spontaneous clearance of infection (p < 0.05). Of 85 IFN-treated cases, 56 achieved sustained virologic response (SVR) whereas 27 were relapsed cases. Among these patients who achieved SVR, a favorable CC/TT allele at rs12979860/rs8099917 was found to be predominant with 76.79 and 66.07%, respectively, whereas in the case of relapsed patients, unfavorable CT (55.56%) and TG (59.26%) alleles were found to be predominant. Additionally, low serum ferritin level was significantly associated with SVR. CONCLUSION: CC at rs12979860 and TT at rs8099917 was strongly associated with spontaneous clearance and SVR in the population with thalassemia. Low age group and low serum ferritin level are important cofactors. This allelic pattern will aid clinicians in making an informed decision about prognosis and therapeutic management.

Recombination in hepatitis C virus is not uncommon among people who inject drugs in Kolkata, India.

Recombination in RNA virus is a rare event in the survival and evolution to evade host immune system. This is increasing within high risk group population (HRG) due to super infection that occurs by continuous sharing of common drug equipment by HCV infected or HIV-HCV co-infected recurrent drug users. Recombination causes impediment to vaccine development and therapeutic intervention as standard HCV treatment is still genotype specific. Blood samples of 194 people who inject drugs (PWID) were collected from an Opioid Substitution Therapy Centre in Kolkata, India. HCV sero-reactivity was checked by ELISA. Detection of HCV RNA by nested RT-PCR and genotyping by DNA sequencing were done. Phylogenetic analysis, Simplot, Bootscan plot, Recombination Detection Program were used for recombinant strain identification. Out of 80 HCV sero-reactive samples, 77 were RNA positive (96.25%). Out of 74 HIV mono-infected individuals, 12 HCV sero-nonreactive samples were HCV RNA positive. Out of total 89 RNA positive samples, 64 paired partial core and NS5B region (71.9%) were sequenced by Sanger's method. Two major genotypes (1 and 3), four subtypes and an inter-genotype recombinant strain (3a/1a) with a novel breakpoint in the NS4B coding region were found.