■以前的研究表明PD-1/PD-L1抑制剂在慢性HBV感染治疗中的潜力。然而,由于III期临床试验尚未公布,通过观察接受PD-1抑制剂治疗的癌症患者血清乙型肝炎表面抗原(HBsAg)和HBV-DNA水平的变化,可以获得更多的临床见解。
■探讨PD-1抑制剂联合治疗对血清HBsAg和HBV-DNA水平的影响,调查HBsAg消失的发生率,HBV再激活(HBVr),和免疫相关不良事件(irAE),并确定与显著HBsAg波动和HBVr相关的危险因素。
■进行了一项回顾性研究,包括2019年7月至2023年6月期间接受PD-1抑制剂的1195名HBsAg阳性癌症患者,180例患者纳入本研究。在不同亚组之间比较PD-1抑制剂给药前后的血清HBsAg水平。进行Pearsonχ2或Fisher精确检验以研究分类变量之间的关系。进行单变量和多变量分析,以确定与显着的HBsAg波动和HBVr相关的危险因素。
■同时使用抗病毒药物,129例患者血清HBsAg水平降低(Z=-3.966,P<0.0001),51例患者血清HBsAg水平升高(t=-2.047,P=0.043)。此外,7例患者(3.89%)取得血清HBsAg消失。大多数入选患者的病毒复制受到抑制。当将患者分为不同的亚组时,显着HBsAg减少后PD-1抑制剂给药后发现较低基线HBsAg组(Z=-2.277,P=0.023),HBeAg血清阴性组(Z=-2.200,P=0.028),非IRAE发生组(Z=-2.007,P=0.045)和肝癌组(Z=-1.987,P=0.047)。值得注意的是,11例患者和36例患者经历了HBVr(6.11%)和irAE(20%),分别,这可能导致PD-1抑制剂的停用或延迟使用。经过多变量分析,HBeAg血清阳性(OR,7.236[95%CI,1.757-29.793],P=0.01)和IRAE的发生(OR,4.077[95%CI,1.252-13.273],P=0.02)被确定为HBsAg显著增加的独立危险因素,IRAE的发生(OR,5.560[95%CI,1.252-13.273],P=0.01)被确定为HBVr的唯一独立危险因素。
■PD-1抑制剂联合核苷(酸)类似物(NAs)可能对癌症患者的慢性HBV感染发挥治疗潜力。然而,还应注意HBsAg水平显着升高的风险,HBVr,与PD-1抑制剂联合治疗相关的irAE。
Previous studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy.
To explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr.
A retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr.
With the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr.
PD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy.