肝移植术后乙型肝炎病毒再感染的影响因素研究

The influence factors for hepatitis B virus re-infection after liver transplantation

目的探究肝移植术后乙型肝炎病毒(HBV)感染的影响因素。方法对1998年12月至2002年1月天津市第一中心医院92例HBV感染肝移植患者采用免疫抑制剂和抗生素预防感染等治疗,术后分为单独使用拉米夫定20例和乙型肝炎免疫球蛋白(HBIG)与拉米夫定联合应用72例两组。观察术后肝功能、HBV血清标记物、外周血单个核细胞(PBMC)中HBV DNA、YMDD及HBVS区基因变异、肝组织免疫组化等变化。结果HBV相关肝病肝移植患者乙型肝炎复发率为4.35%(4/92)。单用组HBV感染率为35%(7/20),联合治疗组HBV感染率为6.94%(5/72)。术前HBV DNA阴性者HBV感染率为0;术前HBV DNA阳性者,术后HBV感染率为17.39%(12/69),其中9例发生YMDD或S区基因变异。测定14例患者PBMC中HBV DNA,术前术后HBV DNA均阴性患者,HBV再感染率为11.11%(1/9);术前5例HBV DNA阳性者,术后HBV感染率为80%(4/5);术前术后HBV DNA均阳性者,术后HBV感染率100%(3/3);术前HBV DNA阳性而术后阴性者HBV感染率为50%(1/2)。结论单用拉米夫定预防肝移植术后HBV感染,较HBIG联合拉米夫定组容易造成HBV再感染。术前血清HBV DNA阳性、术前术后YMDD和S区基因变异以及PBMC中HBV DNA阳性是影响术后HBV再感染感染的主要因素。

Objective To study the influence factors for HBV reinfection following liver transplantation. Methods 92 cases of liver transplantation were enrolled for open non-randomized clinical study. Given conventional OLTx and immunosuppressive agents and antibiotics to prevent infection etc, patients are divided into lamivudine alone and HBIG combined with lamivudine group. Observation of postoperative liver function, HBV serum markers, HBV DNA in PBMC, YMDD and HBV S gene mutation,liver tissue IH etc. Results In 92 cases of liver transplantation with HBV-related liver disease, hepatitis B recurrence rate was 4. 35% （4/92）. In lamivudine group the HBV infection rate was 35% （7/20） ;In combined therapy group the HBV infection rate was 6.94% （5/72）. With preoperatively negative HBV DNA negative the hepatitis B recurrence rate was 0 ; With preoperatively positive HBV DNA, the postoperative HBV infection rate was 17.39% （12/69） ,which had cases with S gene or YMDD mutation. In patients with negative HBV DNA before and after operation,the HBV re-infection rate was 11.11% （1/9） ;In 5 cases with preoperative HBV DNA positive,the HBV infection rate was 4/5 after LTx;before and after operation HBV DNA are positive,the HBV infection rate was 100% （3/3） ; the preoperative HBV DNA positive and postoperative HBV DNA negative, the HBV infection rate was 50% （1/2）. Conclusion To prevent HBV infection after LTx, lamivudine group easily leads to HBV re-nfection than HBIG combined with lamivudine group. Preoperative serum HBV DNA positive, preoperative and postoperative HBV YMDD and S gene mutation are the primary factors affecting the HBV re-infection after operation. HBV DNA positive in PBMC is the source of HBV re-infection,but also the factor of recurrence of hepatitis B.