Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence

Abstract

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre-or post-LT DAA effect). From 994 included patients, 50.6% were HCV−, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alphafetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre-or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT. LiverTransplantation 26 640-650 2020 AASLD. PiñerO et al. liver transPlantatiOn, vol. 26, no. 5, 2020 PiñerO et al.

Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma

“…The median AFP at diagnosis for our center has declined annually from 34 ng/mL in 2016, to 15 ng/mL in 2017, and 8.4 ng/mL in 2018. Despite these trends in early-stage diagnosis and AFP biomarker levels, first-line ORR in bridge to LT remains highly variable in the literature (23%–94%) [ 27 , 28 , 29 , 30 , 31 , 32 ], with up to 25% of candidates experiencing HCC progression while awaiting LT [ 33 , 34 , 35 ]. With a potentially increasing incidence of AFP negativity and AFP <20 ng/mL, the ability to assess baseline prognosis using a single biomarker will become extremely limited.…”

Hepatocellular carcinoma and hepatitis C virus infection in Latin America: epidemiology, diagnosis and treatment

“…A lower incidence of post-transplant HCC recurrence among HCV + patients treated with pre-or post-LT DAAs was observed [0.7%CI (0.2-4.9)]. Although some patients with DAA treatment developed HCC, DAA treatment was neither associated with increased HCC recurrence after LT nor with waitlist tumor progression [108] .…”

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

“…A study conducted at a center in Padua, Italy did not show any differences in the percentage of dropout patients and in recurrence after LTx in HCC-HCV patients treated with DAA and those that were untreated [ 83 ]. Similarly, a multi-center retrospective study conducted in South America did not report tumor progression in patients treated with DAA awaiting LTx or higher recurrence rates (independent of DAA treatment pre- or postoperatively) in comparison to HCC patients treated for HCV [ 84 ].…”