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Reham Hammad,1 Mona A Eldosoky,1 Alshaimaa M Mosaad,2 Asmaa M El-Nasser,3 Fatma M Kotb,4 Salwa I Elshennawy,1 Noha Abdel-Rahman Eldesoky,5 Mohamed A Selim,6 Gina G Naguib,7 Ossama A Ahmed,7 Mohamed Alboraie,8 Reda Badr Aglan9 1Clinical Pathology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt; 2Hepatogastroenterology and Infectious Diseases Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 3Medical Microbiology and Immunology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt; 4Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 5Biochemistry and Molecular Biology Department, Faculty of Pharmacy (for Girls), Al-Azhar University, Cairo, Egypt; 6Botany and Microbiology Department, Faculty of Science (for Boys), Al-Azhar University, Cairo, Egypt; 7Internal Medicine, Gastroenterology and Hepatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 8Department of internal medicine, Al-Azhar University, Cairo, Egypt; 9Hepatology and Gastroenterology Department, National Liver Institute Menoufia university, Menoufia, EgyptCorrespondence: Mohamed Alboraie, Department of internal medicine, Al-Azhar University, Cairo, Egypt, Tel +20222602687, Fax +20224020184, Email alboraie@azhar.edu.egBackground: Natural killer (NK) and B1a cells are implicated in innate immune surveillance against chronic hepatitis C virus (CHCV). NK group 2D (NKG2D) receptor is important for B cell differentiation. This study was designed to assess whether B1a cells and NK Cells expressing NKG2D are implicated in post-hepatitis C infection hepatocellular carcinoma (post-HCV HCC) and cirrhosis using flow cytometry and investigate the association between NK-expressing NKG2D and B1a in complications of CHCV infection.Methods: In this cross-sectional study, 111 participants were included and divided into the post-HCV HCC (n = 50), post-HCV liver cirrhosis (n = 31), and CHCV (n = 30) groups.Results: The percentage of B1a cells (B1a%) and the mean fluorescence intensity (MFI) of NKG2D (NKG2D MFI) showed a significant increase in the CHCV group compared with those in the post-HCV liver cirrhosis and post-HCV HCC groups (P < 0.05). A positive correlation was observed between NKG2D MFI and B1a% (r = 0.6, P < 0.001). The receiver operating characteristic (ROC) curve revealed that NKG2D MFI and B1a% differentiated between patients with CHCV infection and those with HCC with a sensitivity of 92% and 98%, respectively, and differentiated between patients with CHCV infection and those with liver cirrhosis with a sensitivity of 94% and 90%, respectively.Conclusion: Downregulation of B1a frequency and NKG2D intensity is implicated in the progression of CHCV infection to cirrhosis and HCC. NKG2D receptor is associated with the frequency of circulating B1a cells. NKG2D intensity and B1a% can be used as indicators of CHCV progression.Keywords: B1a cells, chronic hepatitis C, hepatocellular carcinoma, NKG2D