"大三阳"乙肝病人肝移植后抗HBV治疗远期效果分析

目的 通过长期观察大三阳乙肝病人肝移植后在LAM或(和)HBIG预防下其体内HBV标志物的变化.探讨乙肝复发的可能机制,为预防复发及个体化治疗寻找切人点.方法 ELISA、HBV-DNA荧光定量、免疫组化定期检测术前术后各期血清及其供肝活检组织,回顾性观察55例大三阳病人随访中HBV标志物的变化.结果 平均随访69.14个月,共12例乙肝再感染/复发,LAM+HBIG组乙肝复发比率为4.8%(2/42),而LAM组为76.9%(10/13)(P=0.000).联合组1、2、3、4年生存率分别为100%、97.1%、92.7%、92.7%;单用组1、2、3、4年生存率分别为76.9%、69.2%、53.8%、46.2%(P=0.000);前者2年内乙肝复发率<3%,后者1、2、3、4年复发率分别为16.1%、41.3%、66.4%、66.4%(P=0.000).结论 HBIG联合核苷(酸)类似物作为当前最佳的乙肝复发预防方案明显地降低了复发率,治疗依从性差及病毒的自身状态是中国肝移植后乙肝再感染/复发的主要原因.根据治疗过程中病毒自身状态的变化及时调整用药将有助于进一步减少术后乙肝复发.

Long-term prevention of virus recurrence among recipients with HBV active replication following liver transplantation

Objective To investigate the long-term prophylactic outcome in recipients with HBV active replication under LAM or/and HBIG prophylaxis after liver transplantation. Methods The liver biopsy specimens and serum samples were collected during the follow-up. ELISA and chemiluminesent microparticle immunoassay, HBV-DNA fluorescent quantification, immunohisto-chemisty and HBV-DNA in situ hybridization were performed for analysis. The alteration of HBV markers in serial biopsy and sera of 55 recipients were investigated retrospectively. Results The mean time of follow-up was 69.14 months. Twelve cases had hepatitis B virus reinfection after transplanta-tion. The accumulated ratio of hepatitis B virus reinfection was 4.8%(2/42)in LAM+ HBIG group and 76.9%(10/13) in LAM monopropyhlaxis group (P=0.000). The 1-,2-,3- and 4-y survival rates in combined prophylaxis group were 100%, 97.1%, 92.7% and 92.7%, respectively. The 1-,2-,3- and 4-yr survival rates in LAM mono prophylaxis group were 76.9%, 69.2%, 53.8% and 46.2&, re-spectively (P=0.000). The rates of hepatitis B virus reinfection in combination prophylaxis group (1-,2-,3- and 4-yr recurrence rates of 2.4%, 2.4%, 2.4% and 8.5%, respectively) was markedly lower than those in mono prophylaxis group(1-, 2-, 3- and 4-yr recurrence rates of 16.1%, 41.3 %, 66.4% and 66.4%, respectively)(P=0.000). Conclusion Currently HBIG combined with LAM is an optimal prophylatic protocol to reduce the hepatitis B virus reinfection rate. However, poor compli-ance of recipients to a prescribed course of prophylaxis as well as viral status itself is still the main cause of hepatitis B virus reinfection after liver transplantation in China. Compliance education and ad-justing the prophyiatic protocols according to the viral alteration after liver transplantation may help to further decrease the hepatitis B virus reinfection rate.