IMPACT OF TREATMENT WITH TENOFOVIR ALAFENAMIDE (TAF) OR TENOFOVIR DISOPROXIL FUMARATE (TDF) ON HEPATOCELLULAR CARCINOMA (HCC) INCIDENCE IN PATIENTS WITH CHRONIC HEPATITIS B (CHB)

Abstract

Background: Potent antiviral treatment can reduce HCC incidence in patients with CHB. TDF and TAF are first-line treatments, and in Phase 3 studies through 3 years, TAF has shown antiviral efficacy similar to TDF, with higher rates of ALT normalization and no resistance. We evaluated HCC incidence in patients participating in these two ongoing studies . Methods: HBeAg-positive (n=1039) and -negative (n=593) patients with HBV DNA ≥20,000 IU/mL and ALT >60 U/L (males) or >38 U/L (females) were recruited from 190 sites in 20 countries and randomized (2:1) to TAF 25 mg or TDF 300 mg given once daily for up to 3 years, followed by open-label TAF through Year 8 . Patients with hepatic decompensation, co-infection with HCV/HDV/HIV, or evidence of HCC at screening were excluded . HCC was assessed by regular (every 6 months) hepatic ultrasonography introduced after Week 96 and throughout by local standards of care. Standardized incidence ratio (SIR) for HCC was calculated for observed cases relative to predicted risk using the REACH-B model . Results: Through 4 years of follow-up, HCC occurred in 16/1632 patients (0.98%; TAF 7/1093 [0.64%]; TDF 9/539 [1.67%]). Of 16 cases of HCC, 5 and 11 were in cirrhotic and non cirrhotic patients respectively. Median (Q1, Q3) time to HCC onset was 566 (318, 855) days (TAF 747 [392, 1370], TDF 460 [180, 729] days). At baseline, relative to those without HCC, patients with HCC were older (median age 53 vs 40 y; p<0.001), had lower HBV DNA (6.3 vs 7.3 log10 IU/mL; p=0 .041), and were more likely to be cirrhotic (FibroTest score ≥0.75; 31% vs 10%; p=0.004). With treatment (TAF or TDF), HCC incidence was significantly reduced (16 observed vs 35.3 predicted; SIR [95% CI] 0.45 [0.278 -0.740]) [Table]. For TAF-treated patients, a significant risk reduction was seen (7 observed vs 22.4 predicted, SIR [95% CI] 0.31 [0.149-0.655]), whereas with TDF there was a reduction in incidence but it did not achieve significance (9 observed vs 12.9 predicted, SIR [95% CI] 0.7 [0.364, 1.344]). Conclusion: In CHB patients receiving TAF or TDF through 4 years, the incidence of HCC was reduced . Additional follow up is needed to further characterize the impact of long term treatment on HCC risk reduction. [https://doi.org/10.1002/hep.30941]