Recurrence of Hepatocellular Carcinoma (HCC) Following Complete Response with Trans Arterial Chemoembolization with Exposure to Direct Acting Antiviral Agents (DAA)

Introduction: It is well known that hepatitis C virus (HCV) related cirrhosis increases the risk of developing hepatocellular carcinoma (HCC). In the past, sustained virologic response (SVR) following interferon-based treatment for chronic HCV was known to be associated with decreased risk of HCC and HCC recurrence. Now in direct acting antiviral agents (DAA) era, studies have demonstrated contrasting evidence with potential increased risk of HCC recurrence (HCCR) after DAA therapy. Aim of our study is to clarify this evidence of HCC recurrence after complete response with trans arterial chemoembolization (TACE) of HCC with DAA therapy. Methods: This was an IRB-approved retrospective analysis of electronic medical records of adult patients >18 years old from December 2013 to May 2018 Louisiana State University Health Sciences Center-Shreveport. We reviewed 275 charts with diagnosis of HCV cirrhosis and HCC. Twelve patients fulfilled the inclusion criteria of DAA exposure and complete response to TACE for HCC. We evaluated them for HCC recurrence after TACE. Results: HCC recurrence was noted in 5 patients (42% of the cohort) with SVR rate only 80%. In the study cohort, 25% were treated with DAA+ribavirin while the rest with DAA alone. The average Model For End-Stage Liver Disease (MELD) before starting DAA was 11, while the average MELD after achieving SVR stabilized at 10. All patients had liver decompensation in the form of ascites during treatment period. In HCCR group, 60% were HCV genotype 1 and 40% with genotype 3; 40% received Epclusa, 60% Harvoni; 80% were males, 60% caucasian, 20% African American. None had vascular invasion; All achieved complete response to locoregional therapy for HCC with one or more sessions. In those with HCCR, 60% were Child Pugh scores (CTP) A, 20% B and 20% C at the end of treatment. Mean Alpha fetoprotein (AFP) at time of HCC diagnosis in HCCR group was 64.84, significantly higher compared to the study cohort mean AFP of 32.98. Conclusion: Despite successful treatment of HCV with DAA and achieving SVR, HCC recurrence was still observed in our population, most notably in caucasian males. No significant differences appreciated in the HCC and HCV characteristics. AFP appears continues to be prognostic marker. Nevertheless, larger prospective studies are needed to further elucidate the relationship between DAA treatment and recurrence of HCC most importantly the time of recurrence and time of DAA exposure.