Yasunaka Tetsuya, Takaki Akinobu, Yagi Takahito, Iwasaki Yoshiaki, Sadamori Hiroshi, Koike Kazuko, Hirohata Satoshi, Tatsukawa Masashi, Kawai Daisuke, Shiraha Hidenori, Miyake Yasuhiro, Ikeda Fusao, Kobashi Haruhiko, Matsuda Hiroaki, Shinoura Susumu, Yoshida Ryuichi, Satoh Daisuke, Utsumi Masashi, Onishi Teppei, Yamamoto Kazuhide
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hepatol Int. 2011 Mar 25;5(4):918-926. doi: 10.1007/s12072-011-9265-z. eCollection 2011 Dec.
The combination of hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogues has been accepted as the best treatment to control hepatitis B recurrence after orthotopic liver transplantation (OLT). However, the optimal dose of HBIg remains unclear. We have previously reported that high-dose HBIg in the early period followed by low-dose HBIg with nucleos(t)ide analogues offers reliable and cost-effective control of hepatitis B recurrence. The aim of this study was to investigate intrahepatic hepatitis B virus (HBV) reinfection status with our clinically successful protocol.
We quantified levels of intrahepatic HBV covalently closed circular (ccc) deoxyribonucleic acid (DNA) and serum hepatitis B core-related antigen (HBcrAg), a new serological marker that can estimate intrahepatic cccDNA levels. Nucleos(t)ide analogues were administered in all cases.
No patients showed recurrence of hepatitis B surface antigen (HBsAg) or HBV-DNA. However, HBV, cccDNA, and HBcrAg were positive in 57% and 48% of patients after OLT, respectively. Pre-OLT serum HBV-DNA and HBcrAg levels correlated linearly with post-OLT cccDNA levels ( = 0.534, < 0.05, and = 0.634, < 0.05, respectively). High serum HBV-DNA and HBcrAg levels, particularly with >3 log copies/mL and >4 log IU/mL, respectively, at the time of OLT, were associated with high levels of post-OLT cccDNA. Even with our successful protocol, nearly half of patients showed HBV reinfection.
Patients with high serum HBV-DNA and HBcrAg levels before OLT (particularly >3 log copies/mL and >4 log IU/mL, respectively) should be followed with care for HBV recurrence.
乙肝免疫球蛋白（HBIg）与核苷（酸）类似物联合应用已被公认为原位肝移植（OLT）后控制乙肝复发的最佳治疗方法。然而，HBIg的最佳剂量仍不明确。我们之前曾报道，早期使用高剂量HBIg，随后联合核苷（酸）类似物使用低剂量HBIg，可有效且经济地控制乙肝复发。本研究旨在通过我们临床成功的方案调查肝内乙肝病毒（HBV）再感染情况。
我们对肝内HBV共价闭合环状（ccc）脱氧核糖核酸（DNA）水平以及血清乙肝核心相关抗原（HBcrAg，一种可评估肝内cccDNA水平的新型血清学标志物）进行了定量分析。所有病例均使用核苷（酸）类似物。
无患者出现乙肝表面抗原（HBsAg）或HBV-DNA复发。然而，OLT后分别有57%和48%的患者HBV、cccDNA及HBcrAg呈阳性。OLT前血清HBV-DNA和HBcrAg水平与OLT后cccDNA水平呈线性相关（分别为r = 0.534，P < 0.05，以及r = 0.634，P < 0.05）。OLT时血清HBV-DNA和HBcrAg水平较高，尤其是分别>3 log拷贝/mL和>4 log IU/mL时，与OLT后高水平的cccDNA相关。即便采用我们成功的方案，仍有近一半的患者出现HBV再感染。
OLT前血清HBV-DNA和HBcrAg水平较高的患者（尤其是分别>3 log拷贝/mL和>4 log IU/mL）应密切随访观察HBV复发情况。
