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In 2020, we conducted a retrospective analysis involving more than 29,000 patients in Hong Kong with HBV who received treatment with TDF or ETV from January 2008 to June 2018. Patients with other viral coinfections, patients previously treated with nucleos(t)ide analogues or peginterferon, and patients with HCC, other cancers, or liver transplant at baseline or within 6 months thereafter were excluded. The median follow-up period of this study was 3.6 years. After propensity score weighting to make the 2 cohorts with chronic HBV infection comparable, we found that TDF treatment reduced the risk of HCC compared with ETV treatment (subdistribution HR: 0.36; 95% CI: 0.16-0.80; P = .013). This suggests that treatment with TDF can reduce the HCC risk 60% further than treatment with ETV.11