Clinical endpoints
Eligible patients were divided into a low HBV DNA group (low group, ≤
2000 IU/ml) and a high HBV DNA group (high group, > 2000
IU/ml) according to the baseline HBV DNA levels. The primary study end
point was progression-free survival (PFS), which was defined as the time
from the first dose of anti-PD-1 immunotherapy to the first radiological
disease progression or death according to the Response Evaluation
Criteria in Solid Tumours (RECIST) criteria, version 1.1. The secondary
endpoints included HBV reactivation and HBV-associated hepatitis. HBV
reactivation in patients positive for HBsAg was defined according to the
American Association for the Study of Liver Diseases 2018 Hepatitis B
guidance: (1) a ≥ 2 log (100-fold) increase in HBV DNA compared to the
baseline level; (2) HBV DNA ≥ 1000 IU/mL in a patient with a previously
undetectable level. HBV-associated hepatitis was defined as a three-fold
or greater increase in serum ALT or AST than the upper limit of a normal
value or an absolute increase in serum ALT to more than 100 U/L
accompanying or following HBV reactivation. Follow-up computed
tomography (CT) or magnetic resonance imaging (MRI) scans were performed
6–12 weeks after anti-PD1 treatment initiation and approximately 3–6
months thereafter. Serum HBV DNA level was measured with the Cobras
Taqman HBV Kit (Roche Diagnostics; lower limit of detection: 20 IU/mL)
and was also tested at each follow-up visit.