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

Background & Aims: Whether hepatitis B surface antigen (HBsAg) seroclearance provides further clinical benefit over complete viral suppression in nucleos(t)ide analogue (NA)-treated chronic hepatitis B (CHB) patients with cirrhosis remained unclear. We aimed to compare the risk of hepatocellular carcinoma (HCC) and hepatic decompensation in treated cirrhotic patients with complete viral suppression versus HBsAg seroclearance. Approach & Results: All adult patients with CHB 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 5,149 patients (mean age 60.1±12.6 years, 66.3% male) included in the one-year landmark analysis, 456/4,988 (9.1%) and 5/161 (3.1%) of patients with complete viral suppression alone and HBsAg seroclearance developed HCC respectively at a median (25 th -75 th percentile) follow-up of 4.1 (2.5-5.0) years; 334/4,777 (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 hazard ratio [asHR] 0.37, 95%CI 0.15-0.91, p =0.030) but not hepatic events (asHR 1.01, 95%CI 0.52-1.95), than complete viral suppression. Similar results on HCC were observed in two-year landmark analysis (asHR 0.37 [0.14-1.04]). Conclusion: HBsAg seroclearance is associated with a lower risk of HCC but not first/further hepatic decompensation in NA-treated CHB cirrhotic patients with complete viral suppression.