Abstract: Objective To investigate the clinical features of patients with failure or recurrence after treatment with PEG-IFN combined with ribavirin( PR regimen) in the real world and the clinical effect of different direct-acting antiviral agent( DAA) regimens in such patients. Methods A retrospective analysis was performed for the clinical data of 106 patients with chronic hepatitis C or hepatitis C-related compensated liver cirrhosis who attended the outpatient service or were hospitalized in The First Peoples' s Hospital of Lanzhou from March2014 to January 2018,and these patients experienced failure or recurrence after the treatment with the standard PR regimen. There were 54 male and 52 female patients. According to the response to PR treatment,the patients were divided into failure group with 13 patients,recurrence group with 51 patients,and sustained virologic response group with 42 patients. All patients underwent IL-28 B rs12979860/rs8099917 detection,baseline biochemical examination,Cobas HCV RNA test,and viral genotyping,and these results were compared between groups. The clinical outcomes of patients with failure or recurrence after PR treatment were observed after the treatment with different DAA regimens. The chi-square test was used for comparison of categorical data between groups; a one-way analysis of variance was used for comparison between multiple groups. Results The failure group and the recurrence group had a significantly higher age than the sustained virologic response group( F = 14. 05,P < 0. 001). Among the patients in the failure group,86. 4% had viral genotype 1 b,while among those in the recurrence group,72. 5% had viral genotype 2 a,and there was a significant difference between the three groups( χ2=17. 269,P = 0. 002). Among the patients in the failure group,92. 3% had a baseline HCV RNA level of ≥106 IU/L,and the failure group had a significantly higher proportion of such patients than the recurrence group and the sustained virologic response group( χ2= 10. 407,P =0. 005). There were no significant differences in sex and liver cirrhosis between the three groups( all P > 0. 05). Among the patients with primary treatment failure,100% patients had the non-protective genotype of IL-28 B rs12979860 CT/TT,and 92. 3% had the non-protective genotype of IL-28 B rs8099917 TG/GG; among the patients with recurrence,84. 3% patients had the non-protective genotype of IL-28 B rs12979860 CT/TT,and 86. 3% had the non-protective genotype of IL-28 B rs8099917 TG/GG; among the patients in the sustained virologic response group,85. 7% gad genotype CC at IL-28 B rs12979860 and 88. 1% had genotype TT at IL-28 B rs8099917.There were significant differences in the constituent ratios of rs12979860 and rs8099917 gene polymorphisms between the three groups( χ2= 57. 263 and 59. 651,both P < 0. 001). The patients with failure or recurrence after PR treatment achieved a sustained virologic response rate of 100% after the treatment with three different DAA regimens based on sofosbuvir. Conclusion Viral genotype and non-protective genotypes at IL-28 B rs12979860 and rs8099917 are influencing factors for failure and recurrence after PR treatment. The three different DAA regimens based on sofosbuvir achieves a sustained virologic response rate of 100% and has good safety in patients with failure or recurrence after PR treatment,which is not affected by the factors including IL-28 B single nucleotide polymorphism and viral replication level in the host.