KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection
In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/2673-4389/3/3/27 |
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| author | Waleed Abdelmaguid Doha Maher Mohamed A. S. Kohla Sameera Ezzat Inas Moaz Wael S. Abdel-Mageed Khalil A. El-Halfawy Mohamed H. Abdel-Rahman |
| author_facet | Waleed Abdelmaguid Doha Maher Mohamed A. S. Kohla Sameera Ezzat Inas Moaz Wael S. Abdel-Mageed Khalil A. El-Halfawy Mohamed H. Abdel-Rahman |
| author_sort | Waleed Abdelmaguid |
| collection | DOAJ |
| description | In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in the outcome of individuals with chronic hepatitis C virus (HCV) infection in Egypt. The study was carried out under an IRB-approved protocol. Sequence-Specific-Primer-PCR (SSP-PCR) was used for KIR genotyping of germline DNA extracted from peripheral blood leukocytes or from the non-tumor liver of 83 HCC patients, 100 patients with chronic HCV infection without HCC, and 120 matched healthy controls. Out of the 83 HCC patients, only 7 (8.4%) were treated by interferon and/or interferon Ribavirin combination, while for the remaining patients 50 (60.2%) received no prior HCV therapy and 26 (31.3%) were treated with direct-acting antiviral (DAA). Our results showed that KIR haplotype AA that contains more inhibitory KIR genes and fewer activating genes was observed with a significantly lower frequency in HCC patients (6/83, 7.2%) compared to chronic HCV (27/100, 27.0%) (<i>p</i> = 0.0005, OR = 0.21 [0.08–0.53]) and healthy controls (29/119, 24.4%) (<i>p</i> = 0.001, OR = 0.24 [0.09–0.61]). In addition, the frequency of genotype 6 (G6) which contains all the KIR genes was significantly high in the HCC patients (16/83, 19.3%) compared to chronic HCV (8/100, 8.0%) (<i>p</i> = 0.02, OR = 2.7 [1.11–6.79]) and healthy controls (8/119, 6.7%) (<i>p</i> = 0.006, OR = 3.31 [1.35–8.16]). Activating KIR genes 2DS1 and 3DS1 were significantly higher in HCC patients (48/83, 57.83% and 45/83, 54.22%) compared to the chronic HCV patients (36/100, 36% and 34/100, 34%), <i>p</i> = 0.028, 0.027, respectively. Our results are contrary to a prior work on HCC from patients with HCV who were mostly treated by interferon-based therapies. In conclusion, KIR haplotype AA has an important role in host defense against HCC progression especially in patients treated by DAA, suggesting an important role of the KIR genotype status on the outcome of chronic HCV infection. |
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| spelling | doaj.art-ce8d421426cd4690a6d1025009652e682023-11-19T11:38:44ZengMDPI AGLivers2673-43892023-07-013335436810.3390/livers3030027KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C InfectionWaleed Abdelmaguid0Doha Maher1Mohamed A. S. Kohla2Sameera Ezzat3Inas Moaz4Wael S. Abdel-Mageed5Khalil A. El-Halfawy6Mohamed H. Abdel-Rahman7National Liver Institute Sustainable Sciences Institute Collaborative Research Center (NLISSICRC), Menoufia University, Shebin Elkom 32511, EgyptDepartment of Pathology, National Liver Institute (NLI), Menoufia University, Shebin Elkom 32511, EgyptNational Liver Institute Sustainable Sciences Institute Collaborative Research Center (NLISSICRC), Menoufia University, Shebin Elkom 32511, EgyptNational Liver Institute Sustainable Sciences Institute Collaborative Research Center (NLISSICRC), Menoufia University, Shebin Elkom 32511, EgyptEpidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom 32511, EgyptDepartment of Genetics, Faculty of Agriculture, Beni-Suef University, Beni Suef 62521, EgyptDepartment of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City 2897, EgyptNational Liver Institute Sustainable Sciences Institute Collaborative Research Center (NLISSICRC), Menoufia University, Shebin Elkom 32511, EgyptIn Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in the outcome of individuals with chronic hepatitis C virus (HCV) infection in Egypt. The study was carried out under an IRB-approved protocol. Sequence-Specific-Primer-PCR (SSP-PCR) was used for KIR genotyping of germline DNA extracted from peripheral blood leukocytes or from the non-tumor liver of 83 HCC patients, 100 patients with chronic HCV infection without HCC, and 120 matched healthy controls. Out of the 83 HCC patients, only 7 (8.4%) were treated by interferon and/or interferon Ribavirin combination, while for the remaining patients 50 (60.2%) received no prior HCV therapy and 26 (31.3%) were treated with direct-acting antiviral (DAA). Our results showed that KIR haplotype AA that contains more inhibitory KIR genes and fewer activating genes was observed with a significantly lower frequency in HCC patients (6/83, 7.2%) compared to chronic HCV (27/100, 27.0%) (<i>p</i> = 0.0005, OR = 0.21 [0.08–0.53]) and healthy controls (29/119, 24.4%) (<i>p</i> = 0.001, OR = 0.24 [0.09–0.61]). In addition, the frequency of genotype 6 (G6) which contains all the KIR genes was significantly high in the HCC patients (16/83, 19.3%) compared to chronic HCV (8/100, 8.0%) (<i>p</i> = 0.02, OR = 2.7 [1.11–6.79]) and healthy controls (8/119, 6.7%) (<i>p</i> = 0.006, OR = 3.31 [1.35–8.16]). Activating KIR genes 2DS1 and 3DS1 were significantly higher in HCC patients (48/83, 57.83% and 45/83, 54.22%) compared to the chronic HCV patients (36/100, 36% and 34/100, 34%), <i>p</i> = 0.028, 0.027, respectively. Our results are contrary to a prior work on HCC from patients with HCV who were mostly treated by interferon-based therapies. In conclusion, KIR haplotype AA has an important role in host defense against HCC progression especially in patients treated by DAA, suggesting an important role of the KIR genotype status on the outcome of chronic HCV infection.https://www.mdpi.com/2673-4389/3/3/27chronic hepatitis CEgyptiangenotypinghepatocellular carcinomaKIRSSP-PCR |
| spellingShingle | Waleed Abdelmaguid Doha Maher Mohamed A. S. Kohla Sameera Ezzat Inas Moaz Wael S. Abdel-Mageed Khalil A. El-Halfawy Mohamed H. Abdel-Rahman KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection Livers chronic hepatitis C Egyptian genotyping hepatocellular carcinoma KIR SSP-PCR |
| title | KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection |
| title_full | KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection |
| title_fullStr | KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection |
| title_full_unstemmed | KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection |
| title_short | KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection |
| title_sort | kir genotypes impact progression to hepatocellular carcinoma in patients with chronic hepatitis c infection |
| topic | chronic hepatitis C Egyptian genotyping hepatocellular carcinoma KIR SSP-PCR |
| url | https://www.mdpi.com/2673-4389/3/3/27 |
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