Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss
Yan Xue 1 , Meng Zhang 1 , Tao Li 1 , Feng Liu 2 , Li-Xin Zhang 1 , Xiao-Ping Fan 1 , Bao-Hua Yang 1 , Lei Wang 3
Affiliations
Affiliations
1
Department of Infectious Disease and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China.
2
Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300000, China.
3
Department of Infectious Disease and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China. [email protected].
Background: Nucleos(t)ide analogs (NAs) cessation in chronic hepatitis B (CHB) patients remains a matter of debate in clinical practice. Current guidelines recommend that patients with hepatitis B e antigen (HBeAg) seroconversion discontinue NAs after relatively long-term consolidation therapy. However, many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg, even if hepatitis B surface antigen (HBsAg) loss occurs. It remains unclear whether NAs can be discontinued in this subset of patients.
Aim: To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss (without hepatitis B e antibody) after cessation of NAs.
Methods: We studied patients who discontinued NAs after achieving HBeAg loss. The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs. The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves; we confirmed the cut-off value of HBsAg according to a previous study. The log-rank test was used to compare cumulative relapse rates among groups. We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates. Propensity score matching analysis (PSM) was used to balance baseline characteristics between the groups.
Results: We included 83 patients with HBeAg loss. The mean age of these patients was 32.1 ± 9.5 years, and the majority was male (67.5%). Thirty-eight patients relapsed, and the cumulative relapse rate at months 3, 6, 12, 24, 36, 60, 120, and 180 were 22.9%, 36.1%, 41.0%, 43.5%, 45.0%, 45.0%, 45.0%, and 52.8%, respectively. Twenty-six (68.4%) patients relapsed in the first 3 mo after NAs cessation, and 35 patients (92.1%) relapsed in the first year after NAs cessation. Consolidation period (≥ 24 mo vs < 24 mo) (HR 0.506, P = 0.043) and HBsAg at cessation (≥ 100 IU/mL vs < 100 IU/mL) (HR 14.869, P = 0.008) were significant predictors in multivariate Cox regression. In the PSM cohort, which included 144 patients, there were lower cumulative relapse rates in patients with HBeAg seroconversion (P = 0.036).
Conclusion: HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation, especially in patients with HBsAg at cessation < 100 IU/mL. Careful monitoring, especially in the early stages after cessation, may ensure a favorable outcome.
Keywords: Cessation; Chronic hepatitis B; Hepatitis B e antigen; Nucleos(t)ide analogs.
结果:我们纳入了83例HBeAg丢失的患者。这些患者的平均年龄为32.1±9.5岁,大多数为男性(67.5%)。 38例患者复发,第3、6、12、24、36、60、120和180个月的累积复发率分别为22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0% ,和52.8%。停止NAs后的前3个月中有26例(68.4%)复发,而停止NAs后的第一年中有35例(92.1%)复发。巩固期(≥24 mo vs <24 mo)(HR 0.506,P = 0.043)和停药时HBsAg(≥100 IU / mL vs <100 IU / mL)(HR 14.869,P = 0.008)是多变量Cox的重要预测指标回归。在包括144名患者的PSM队列中,HBeAg血清转化患者的累积复发率较低(P = 0.036)。
结论:HBeAg阳性的HBeAg丢失的CHB患者在长期巩固后可能能够停止NAs治疗,尤其是在HBsAg停止<100 IU / mL的患者中。仔细的监测,尤其是在戒烟后的早期阶段,可以确保取得良好的结果。