Ueda Yoshihide, Marusawa Hiroyuki, Egawa Hiroto, Okamoto Shinya, Ogura Yasuhiro, Oike Fumitaka, Nishijima Norihiro, Takada Yasutsugu, Uemoto Shinji, Chiba Tsutomu
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Antivir Ther. 2011;16(4):479-87. doi: 10.3851/IMP1771.
De novo activation of HBV occurs after liver transplantation from hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)-positive donors, even under hepatitis B immunoglobulin (HBIG) prophylaxis. One reason for the activation of HBV is the emergence of HBV with escape mutations from hepatitis B surface antibody (anti-HBs). The aim of this study is to clarify the clinical features for de novo activation of HBV with anti-HBs escape mutations after liver transplantation.
Clinical features of 75 patients who received HBIG prophylaxis >6 months after liver transplantation with liver grafts from anti-HBc-positive donors were retrospectively analysed.
Among the 75 recipients, 19 (25%) developed de novo activation of HBV. Of the 19 recipients, the emergence of HBV with anti-HBs escape mutations was confirmed in 7 patients. The rate of de novo activation of HBV with anti-HBs escape mutations was 12% at 5 years. Sequence analysis revealed mutations in the common 'a' determinant region of the surface gene, including G145R, G145A and Q129P, in HBsAg. Administration of entecavir immediately after the occurrence of de novo HBV activation resolved hepatitis and induced clearance of serum HBsAg and HBV DNA in all four patients receiving entecavir.
Escape mutations from anti-HBs caused de novo activation of HBV under HBIG prophylaxis after liver transplantation. Early administration of entecavir was effective on de novo activation of HBV with anti-HBs escape mutations.
即使在使用乙肝免疫球蛋白（HBIG）预防的情况下，从乙肝表面抗原（HBsAg）阴性且乙肝核心抗体（抗-HBc）阳性的供体进行肝移植后，仍会发生乙肝病毒（HBV）的重新激活。HBV激活的一个原因是出现了对乙肝表面抗体（抗-HBs）具有逃逸突变的HBV。本研究的目的是阐明肝移植后具有抗-HBs逃逸突变的HBV重新激活的临床特征。
回顾性分析了75例肝移植后接受HBIG预防超过6个月且肝移植来自抗-HBc阳性供体的患者的临床特征。
在75例接受者中，19例（25%）发生了HBV的重新激活。在这19例接受者中，7例被证实出现了具有抗-HBs逃逸突变的HBV。5年时具有抗-HBs逃逸突变的HBV重新激活率为12%。序列分析显示，HBsAg表面基因的常见“a”决定簇区域发生了突变，包括G145R、G145A和Q129P。在HBV重新激活发生后立即给予恩替卡韦，在所有4例接受恩替卡韦治疗的患者中，肝炎得到缓解，血清HBsAg和HBV DNA清除。
抗-HBs的逃逸突变在肝移植后HBIG预防的情况下导致了HBV的重新激活。早期给予恩替卡韦对具有抗-HBs逃逸突变的HBV重新激活有效。
