Effect of treatment of hepatitis B patients with tenofovir disoproxil or entecavir on risk of hepatocellular cancer death in a U.S. Cohort
Gordon SC, Zhou Y, Li J, Rupp LB, Boscarino JA, Daida YG, Schmidt MA, Trudeau S, and Lu M. Effect of treatment of hepatitis B patients with tenofovir disoproxil or entecavir on risk of hepatocellular cancer death in a U.S. Cohort. Journal of Hepatology 2019; 70(1 Suppl ):e147.
Background and aims: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line treatment in patients with chronic hepatitis B (CHB). A recent study from Asia showed that treatment-naïve patients who started treatment with TDF had significantly lower risk of HCC compared to those who received treatment with ETV (HR = 0.61 and 95% confidence interval [CI] were 0.54-0.7). We used data from the longitudinal Chronic Hepatitis Cohort Study (CHeCS) to validate these findings in a US population that included both Asian and non-Asian patients. Method: After excluding patients with liver transplant, HIV, or history of treatment with both ETV and TDF, we followed 822 CHB patients treated with either TDF (n = 407) or ETV (n = 415) for incidence of HCC and all-cause mortality. Cox regression was used to compare treatment effects and inverse probability treatment weighting (IPTW)—which included index age, sex, race, Fibrosis-4 score, and cirrhosis—was used to adjust for treatment selection bias. Death was considered a competing risk for HCC. The analysis was stratified by race (Asian or non-Asian). A subgroup analysis was conducted among previously treatment-naïve patients. Results: Among 822 included CHB patients, 164 (20%) had previously received other antiviral treatment before starting TDF or ETV, 151 (18%) had cirrhosis, and 517 (63%) were Asian. Median follow-up was 3 years. The p value for race-by-treatment interaction was 0.17 for HCC and 0.30 for mortality. In the Asian group, the adjusted Hazard Ratios (aHR) for TDF versus ETV (95%CI) were 0.70 (0.29, 1.68) for HCC and 0.86 (0.48, 1.53) for mortality. In the non-Asian group, aHRs (95% CI) were 1.87 (0.60, 5.87) for HCC, and 1.25 (0.81, 1.92) for mortality. Results were similar in the treatment naïve patients (n = 677): among Asians, aHRs (95% CI) were 0.73, (0.29, 1.84) for HCC and 0.94 (0.51, 1.73) for mortality; in the non-Asian group, aHR (95% CI) were 1.21 (0.37, 3.98) for HCC and 1.17 (0.72, 1.90) for mortality. Conclusion: We observed that risk of HCC among patients treated with TDF compared to those treated with ETV may vary by race group. Among Asian patients in our cohort, an adjusted hazard ratio = 0.70 (TDF vs. ETV) suggests a trend toward HCC risk reduction, consistent with the results published from Asia. There was no treatment-related difference in mortality risk between the two race groups. These findings need to be validated in a larger cohort.