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Background and objective: IL28B-gene polymorphisms show inconclusive relationships with CHCV DAAs-treatment outcomes on evaluation by serum-PCR. Solitary intra-PBMCs HCV-RNA antisense-strands are independently found in naïve and experienced cases regardless to viremia or hepatic-parenchymal changes. We correlated frequencies of IL28B-gene SNPs and alleles with HCV induced liver-changes during SVR evaluation by PBMCs-PCR after DAAs-therapy. Methods: Twelve weeks after completing DAAs-therapy, the impacts of IL28B-gene-SNPs were evaluated in three groups of patients: group-I (n=25) with negative serum and PBMCs HCV-PCR, group-II (n=52) had solitary intra-PBMCs HCV-RNA, and group-III (n=25) had positive serum HCV-RNA. All cases were subjected to IL28B-gene-SNP analyses and correlated with their ultrasonographic liver changes.Results: IL28B-genotyping in post-DAAs-treatment HCV-SVR and viral relapse revealed: a) dominant CC-genotype and C allele in normal hepatic parenchyma in group-I compared to group-II (P=0.0047, 0.0007) and group-III (P=0.0564, 0.000003) b) frequent CT-SNP and T-allele in bright hepatic parenchyma in group-II when compared with group-I (P=0.0077, 0.002 ) and group-III (P=0.0363, 0.0005) c) increased TT-SNP and T-allele frequencies in coarse liver in group-III compared to group-I (P=0.02256, 0.000130) and group-II (P=0.08647, 0.004308). Conclusions: Outcomes of HCV treatment with DAAs are dependent on host IL28B-gene polymorphisms and HCV induced liver changes. SVR is achieved when wild type-CC-genotype and C-allele are dominant in normal hepatic parenchyma; solitary intra-PBMCs-relapse occurs in increased frequency of CT-genotype when liver tissues are fibrotic; serologic-relapse is dominant when TT-genotype and T-allele are frequent in cirrhotic liver. IL28B-gene SNP analyses in relation to hepatic parenchymal changes are recommended before treating CHCV-infection with DAAs.