Yong Chee-Chien, Lin Yu-Hung, Espinosa Wendell Z, Chen I-Hsuan, Wang Shih-Ho, Chan Yi-Chia, Chen Chao-Long, Lin Chih-Che
Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan.
Chang Gung University College of Medicine, Taiwan.
Int J Surg. 2024 Oct 1;110(10):6702-6710. doi: 10.1097/JS9.0000000000001801.
Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation. However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated.
Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Antiviral therapy was given to patients with pretransplant anti-HBs <1000 IU/ml (nonrobust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs >1000 IU/ml, while antiviral therapy was not given in patients with an anti-HBs titer over 1000 IU/ml. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates.
Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2 vs 93.4%, P =0.026; 85.1 vs 93.4%, P =0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and nongraft mortality values (90.8 vs 96.6%, P =0.036; 93.0 vs 98.3%, P =0.011, respectively).
Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.
主动免疫接种已被用于预防肝移植后抗-HBc（+）移植物中的新发乙型肝炎病毒感染（DNHB）。然而，主动免疫接种的长期疗效以及抗-HBc（+）移植物的移植物/患者结局尚未得到全面研究。
在纳入该研究的204例儿科患者中，82例接受了抗-HBc（+）移植物。为预防DNHB，在移植前反复进行主动免疫接种。对于移植前抗-HBs<1000 IU/ml（反应不强烈）的患者给予抗病毒治疗2年，当移植后患者抗-HBs>1000 IU/ml时停药，而抗-HBs滴度超过1000 IU/ml的患者不给予抗病毒治疗。主要结局是研究主动免疫接种的长期疗效，次要结局包括移植物和患者生存率。
在82例抗-HBc（+）移植患者中，68%的受者获得了强烈的免疫反应，因此无需抗病毒治疗。2例患者（2.4%）发生了DNHB感染，其中1例是由于逃逸突变体。中位随访150个月，抗-HBc（+）移植物受者的10年总体患者和移植物生存率显著低于抗-HBc（-）移植物受者（分别为85.2%对93.4%，P =0.026；85.1%对93.4%，P =0.034）。此外，排除早期死亡率和非移植物死亡率后，抗-HBc（+）移植物受者的10年患者和移植物结局显著差于抗-HBc（-）移植物受者（分别为90.8%对96.6%，P =0.036；93.0%对98.3%，P =0.011）。
我们的长期随访研究表明，主动免疫接种是一种针对抗-HBc（+）移植物患者DNHB感染的简单、经济有效的策略，从而消除了终身抗病毒治疗的必要性。值得注意的是，抗-HBc（+）移植物和患者的长期生存率均较低，尽管确切机制尚不清楚。
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