Hepatocellular Carcinoma Occurrence and Recurrence in Hepatitis C-infected Patients Treated with Direct-acting Antivirals

Introduction Multiple studies have shown the efficacy of the new direct-acting antivirals (DAAs) with a cure rate of over 90% in hepatitis C virus (HCV)-infected patients. Some recently published studies have suggested an increased incidence of de novo and recurrent hepatocellular carcinoma (HCC) in cirrhotic patients in sustained virological response (SVR) after completing therapy. A possible mechanism is the breakdown of immune surveillance after starting DAAs. We report a retrospective analysis on a population of chronic HCV infected patients, with and without a prior history of HCC, who developed HCC after receiving DAAs in the hope of adding to existing literature and in pursuit of greater clarity into this emerging concern with DAAs. Methods We analyzed 497 HCV-infected patients who were treated with DAAs, or a combination of DAA with interferon, from January 2014 to April 2017 at the Veterans Medical Center, Oklahoma City. Descriptive analysis, including the mean and standard deviation for different variables, was used. The cohort was divided into two groups: cirrhotic and non-cirrhotic. The analysis was run in the cirrhotic group between the subgroups who developed HCC and who did not. Results Data from a total of 233 cirrhotic patients were analyzed. We further subdivided these patients into those who eventually were diagnosed with HCC (group 1) and those who were not (group 2). These subgroups were comparable in regards to race, gender, baseline serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, sodium, HCV genotypes, and pretreatment viral load. All patients completed therapy. The rate of SVR was much lower in group 1 compared to group 2 (62.5% vs 88.94%, p = 0.002), respectively. Model End-stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, and Fibrosis-4 (FIB-4) score were higher in the group that developed HCC. The average time period (weeks) from DAA therapy to HCC diagnosis was 48.2 weeks. The remaining 264 non-cirrhotic patients had no reported cases of HCC. Conclusion From a total of 497 treated HCV-infected patients, 233 (46.88 %) had cirrhosis, out of which 16 (6.86%) were reported to develop HCC during or after DAA therapy was initiated. The remaining 217 (93.1%) cirrhotic patients did not develop HCC. As per our comparison, achieving SVR in cirrhotic patients should not preclude HCC screening, and more studies are needed to assess the risk of HCC in patients who achieve SVR but have a high FIB-4 score. In fact, patients who do not achieve SVR may be at a higher risk of eventually developing HCC and may be candidates for closer surveillance.