Veerappan Annapoorani, VanWagner Lisa B, Mathew James M, Huang Xuemei, Miller Joshua, Lapin Brittany, Levitsky Josh
Department of Medicine - Division of Gastroenterology and Hepatology, 251 East Huron Street Galter Suite 3-150, Chicago, IL 60611, United States.
Department of Medicine - Division of Gastroenterology and Hepatology, 251 East Huron Street Galter Suite 3-150, Chicago, IL 60611, United States; Department of Preventive Medicine, 680 N. Lake Shore Drive Suite 1400, Chicago, IL 60611, United States; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), 676 N. St. Clair 19th Floor, Chicago, IL 60611, United States.
Hum Immunol. 2016 Apr;77(4):367-74. doi: 10.1016/j.humimm.2016.02.009. Epub 2016 Feb 23.
Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects. We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions. In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5-2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection.
从历史上看，与无乙肝病毒（HBV）的肝移植（LT）受者相比，HBV肝移植受者发生急性细胞排斥反应（ACR）的情况较少。鉴于乙肝免疫球蛋白（HBIG）具有体外免疫调节作用，我们质疑在HBIG使用减少的时代这种情况是否仍然存在。我们比较了40593例患有HBV、丙型肝炎、脂肪性肝炎和免疫性肝病的初次肝移植受者（器官获取与移植网络2000 - 2011年数据）中ACR的发生率、危险因素和结局。我们还使用混合淋巴细胞反应评估了HBIG对同种异体免疫淋巴细胞增殖和调节性T细胞生成的体外作用。在多变量分析中，HBV状态仍然是免于ACR的强有力独立预测因素（比值比0.58，95%置信区间：1.5 - 2.1）。除HBV外，ACR患者的全因患者生存率（67.7%对72.3%）和移植物生存率（60.8%对69.1%）显著低于无ACR患者。HBIG的使用与ACR无统计学关联。在体外，相当于临床给药浓度的HBIG不抑制淋巴细胞增殖或促进调节性T细胞发育。总之，通过我们的体外和体内分析，HBV肝移植受者中ACR的发生率和影响现在较低，且似乎并非由HBIG所致。相反，这可能是由于慢性HBV感染固有的免疫抑制特性。
