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Background Treatment of HCV with directly acting antiviral agents (DAAs) is associated with a significant reduction in cardiovascular, metabolic and cancer risk. However, there are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after DAA treatment. Risk of HCC in HCV genotype 3 infected persons after DAA therapy is not well known. Methods We prospectively studied HCV-infected persons initiated on treatment between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. The occurrence of HCC was confirmed based on radiologic findings on a triphasic CT on 64 slice MDCT scanner. The treatment regimen was at the discretion of clinical care providers, taking into account the national guidelines and patient preferences. Patients were followed for 24 weeks after the completion of therapy. Informed consent was obtained from all participants. Results A total of 662 persons were initiated on treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic with 90% of cirrhotics having compensated cirrhosis. 91% were genotype 3 and SVR was attained in 91.9%. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCL), 10.6%; SOF/DCL, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the six month period after treatment completion, and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85) while SOF/RBV/DCL regimen (compared with SOF/RBV/PEG-IFN) was associated with an increased risk of HCC (HR, 95% CI: 17.32, 2.14,140.36). In K-M plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCL, or SOF/DCL regimens had shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. (See figure) Conclusion In a predominantly genotype 3 cohort, incident HCC occurs commonly and early after treatment completion, and exclusively in those with pretreatment cirrhosis. SVR reduces but does not completely eliminate the risk of HCC. Treating HCV-infected persons before the development of cirrhosis may reduce future risk of HCC. Disclosures All authors: No reported disclosures.

304. Hepatocellular Carcinoma Occurs Frequently and Early After Treatment in HCV Genotype 3 Infected Persons Treated with DAA Regimens