Takaki Akinobu, Yasunaka Tetsuya, Yagi Takahito
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Department of Gastroenterological Surgery Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Int J Mol Sci. 2015 Jul 30;16(8):17494-513. doi: 10.3390/ijms160817494.
Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed.
乙型肝炎常进展为失代偿期肝硬化,需要进行原位肝移植(OLT)。尽管新型核苷(酸)类似物可使90%以上的病毒和肝炎活动得到控制,但严重失代偿的患者仍因耐药病毒、急性加重或肝细胞癌而需要OLT。急性乙型肝炎也是OLT的适应证,因为它可进展为致命的急性肝衰竭。OLT后,若不进行预防,乙型肝炎复发率超过80%,而超过90%的移植受者通过联合使用乙型肝炎免疫球蛋白(HBIG)和核苷(酸)类似物治疗可得到临床控制。然而,长期使用HBIG存在几个尚未解决的问题,包括供应有限和成本极高;因此,人们研究了几种低剂量HBIG联合核苷(酸)类似物的治疗方案。另一种方法是使用乙肝病毒包膜(HBs)抗原疫苗诱导自身产生抗乙肝病毒(HBV)抗体。非HBV携带者,如急性感染性肝衰竭患者,是疫苗接种的良好对象。对于慢性HBV携带者肝硬化患者,只有部分患者,如那些采用实验性降低免疫抑制方案治疗的患者,才能成功产生疫苗应答。本文综述了OLT后HBV控制的现行方案以及新型治疗策略的未来前景。