HBsAg seroclearance further reduces hepatocellular carcinoma but not hepatic decompensation in patients with cirrhosis and complete viral suppression

BACKGROUND AND AIMS: Whether HBsAg seroclearance provides further clinical benefit over complete viral suppression in nucleos(t)ide analogue (NA)-treated patients with chronic hepatitis B with cirrhosis remained unclear. We aimed to compare the risk of HCC and hepatic decompensation in treated patients with cirrhosis with complete viral suppression versus HBsAg seroclearance. APPROACH AND RESULTS: All adult patients with chronic hepatitis B and cirrhosis receiving entecavir/tenofovir between January 2005 and September 2020 were identified. Patients with HCC before or within the first 6 months of baseline, other cancers or liver transplantation before baseline, liver transplantation before HBsAg loss, and without complete viral suppression were excluded. One-year landmark analyses were performed; patients with clinical outcomes or follow-up <1 year were excluded. Of 5149 patients (mean age 60.1±12.6 y, 66.3% male) included in the 1-year landmark analysis, 456/4988 (9.1%) and 5/161 (3.1%) of patients with complete viral suppression alone and HBsAg seroclearance developed HCC, respectively, at a median (25th-75th percentile) follow-up of 4.1 (2.5-5.0) years; 334/4777 (7.0%) and 10/153 (6.5%) patients with complete viral suppression and HBsAg loss developed hepatic events. HBsAg seroclearance was associated with a lower risk of HCC (adjusted subdistribution HR: 0.37, 95% CI 0.15-0.91, p =0.030) but not hepatic events (adjusted subdistribution HR: 1.01, 95% CI: 0.52-1.95) than complete viral suppression. Similar results on HCC were observed in a 2-year landmark analysis (adjusted subdistribution HR: 0.37 [0.14-1.04]). CONCLUSIONS: HBsAg seroclearance is associated with a lower risk of HCC but not first/further hepatic decompensation in NA-treated patients with chronic hepatitis B and cirrhosis with complete viral suppression.