De novo Occurrence and Recurrence of HCC in HCV Infected Patients Treated With DAAʼs: A Single Center 2-Year Experience

Abstract

Introduction: Multiple studies have shown the efficacy of new direct-acting antivirals (DAA) with cure rate of over 90% in HCV infected patients. Recently published studies have suggested increased incidence of de novo and recurrent HCC(Hepatocellular carcinoma) in cirrhotic patients in SVR(sustained virological response) after completing therapy. A possible mechanism is breakdown of immune surveillance after starting DAA. We report a small case series in a population of chronic HCV infected patients, with and without prior history of HCC, who developed HCC after receiving direct acting antivirals (DAAs) with the aim of adding to existing literature.Table: Table. Clinical Variables Related To HCV and HCCTable. DAA: therapy associated variablesMethods: We retrospectively reviewed 16 patients reported to have HCC out of 290 patients who were treated with DAA at the Oklahoma City VA Medical Center over 2 years (2014-2015). Descriptive analysis including mean and standard deviation for different variables was performed. Results: All 16 patients were male, with the majority (75%) being white. Mean age was 66 years. All patients had cirrhosis as indicated by Fib-4 score > 3.25 and confirmed by imaging. Average Fib-4 score was 7.88. Most were Child Pugh Class A, with average MELD of 11. 6 (37.5%) were treatment naïve. Majority, 9 (56.25%) were genotype 1a. The frequencies of other HCV genotypes 1b, 2 and 3 were 3 (18.75%), 2 (12.5%) and 2 (12.5%) respectively. The median pretreatment HCV viral load was 1,286,176. EVR(Early viral response) was achieved in all patients. ETR(end treatment response) and Sustained Viral Response (SVR) was achieved in 12 (75%) and 10 (62.5%) patients respectively. In patients who achieved SVR, average number of weeks from SVR to HCC detection was 33.3 weeks. All HCC were diagnosed on surveillance ultrasound (USG) imaging (6 monthly) later confirmed via CT-Scan/MRI. 11/16 had denovo occurance of HCC Average time period from DAA therapy to HCC diagnosis was 48.2 weeks. 9/16 patients had more than 1 nodule at diagnosis, and only 7 fulfilled Milan Criteria. Conclusion: Our case series reiterates previously confirmed concern of increased HCC recurrence in patients with history of eradicated HCC. It may be associated with more aggressive occurance (given multiple nodules in >50% patients). It also adds to growing literature which suggest SVR may not be protective against HCC occurrence. It is unclear if treatment with DAA leads to increased HCC occurrence. There is a need of statistically stronger studies on larger cohorts before further conclusions are drawn.