Direct-acting antiviral therapy significantly reduces early HCC recurrence: A multicenter u.s. cohort study.
Singal AG, Mehta N, Rich NE, Murphy C, Branch AD, Pillai AA, Hoteit MA, Volk M, Odewole M, Scaglione SJ, Guy JE, Said A, Feld JJ, John B, Frenette CT, Mantry PS, Rangnekar AS, Oloruntoba O, Leise MD, Jou J, Bhamidimarri KR, Kulik LM, Tran TT, Samant HV, Dhanasekaran R, Duarte-Rojo A, Salgia RJ, Eswaran SL, Modi AA, Flores A, Satapathy SK, Wong RJ, Huang A, Misra S, Schwartz ME, Mitrani R, Ho CK, Sharma S, Konjeti VR, Dao A, Nelson K, Gulau M, Delarosa K, Rahim U, Mavuram M, Xie JJ, and Parikh ND. Direct-acting antiviral therapy significantly reduces early HCC recurrence: A multicenter u.s. cohort study. Hepatology 2018; 68:58A-59A.
Background: Direct-acting antiviral (DAA) therapy for hepatitis C (HCV) has a controversial impact on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns among DAA-treated and untreated patients who achieved HCC complete response (CR). Methods: We conducted a North American multicenter retrospective cohort study of patients with HCV-related HCC who achieved CR after resection, ablation, transarterial chemo/radioembolization or radiation therapy from 1/2013 to 12/2016. Patients who received DAA prior to CR or achieved CR via transplant or systemic therapy were excluded. Cox regression was used to examine the association between DAA therapy and time-to-recurrence from CR, with DAA therapy analyzed as a time-varying exposure. Patients were censored at death, transplant or last follow-up. Results: Of 866 HCV-HCC patients from 31 health systems, 355 (41.0%) received DAA therapy and 511 (59.0%) were untreated. DAAtreated patients were older (62.5 vs 61.4, p=0.03), more likely had BCLC 0/A HCC (87.3% vs 77.3%, p=0.001), and more likely received resection or ablation (58.0% vs 42.5%, p<0.001) versus untreated patients, but a similar proportion presented within Milan Criteria (84.5% vs. 83.2%, p=0.60). Median time from HCC treatment to CR was 1.6 months, and 4.9 months from CR to DAA initiation. HCC recurred in 149 (42.0%) DAA-treated and 300 (58.7%) untreated patients-with 49 (32.9%) and 191 (63.6%) considered early recurrence (within 365 days of CR), respectively. Recurrence presented as a new intrahepatic lesion in 86 (58.1%) and 169 (57.1%) patients in each group, respectively. DAA therapy was associated with significantly reduced HCC recurrence risk (HR 0.41, 95%CI 0.32-0.52), adjusting for study site, age, sex, Child Pugh class, AFP level, initial tumor burden and HCC therapy leading to complete response. Results were similar when considering early recurrence only (HR 0.42 95%CI 0.30-0.60). In both groups, most recurrences were within Milan Criteria (91.0% vs 90.6%, p=0.84). A larger proportion of DAA-treated than untreated patients received potentially curative therapy (transplant, resection or ablation) for HCC recurrence (34.2% vs 25.7%, p=0.06). A similar proportion in both groups achieved CR or partial response to treatment of recurrence (49.6% vs 51.0%, p=0.80). Conclusion: In the largest cohort study to date, DAA therapy was associated with significantly reduced HCC recurrence, including early recurrence, after CR. HCC recurrence patterns, including tumor burden and treatment response, were similar in DAAtreated and untreated patients.