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美国的乙型肝炎肝疾病和伴发肝细胞癌的肝移植:乙型肝炎免疫球蛋白和核苷(酸)类似物的应用。

Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues.

机构信息

Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.

出版信息

Liver Transpl. 2013 Sep;19(9):1020-9. doi: 10.1002/lt.23703.

Abstract

Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence. Seven hundred thirty-eight patients underwent transplantation for HBV, and 354 (48.0%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs were the most frequent first site of HCC recurrence, and they were followed by the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence, and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P = 0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC, vascular invasion of the explanted tumor, and post-LT chemotherapy were associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001, respectively). Patients with HBV reinfection were 3.6 times more likely than patients without HBV to have HCC recurrence. These data suggest further study of attempts at LT for patients with HBV and HCC beyond the Milan criteria if their HBV is aggressively and successfully treated.

摘要

乙肝病毒(HBV)再感染在肝移植(LT)后可能有利于肝细胞癌(HCC)的复发,HBV 免疫球蛋白(HBIG)和核苷/核苷酸类似物的联合治疗可能会降低 LT 后 HBV 的复发率。为了研究 HBV、HCC 和生存率之间的关系,我们对 7 家美国移植中心在 1985 年 1 月至 2010 年 12 月期间接受 HBV 治疗的 LT 患者进行了回顾性图表审查。在根据抗病毒治疗策略的演变将患者分为 3 个时期(1985-1994 年、1995-2004 年和 2005-2010 年)后,我们回顾了 16 个变量,以确定生存率与 HCC 复发之间是否存在关联。738 例患者因 HBV 接受移植,其中 354 例(48.0%)同时患有 HCC,58 例(16.4%)HCC 复发。与第 1 期相比,第 3 期的 3 年生存率要好得多(87%比 40%,P=0.001),HCC 复发率也较低(12%比 29%,P=0.009)。HCC 复发的最常见首发部位是肺部,其次是肝脏。多变量分析显示,HBV 再感染、HCC 复发和 HBIG 使用与生存率下降相关(P<0.001、P<0.001 和 P=0.002);HCC 复发和 3 期 HCC 以及其他因素与 HBV 再感染相关(P<0.001 和 P=0.004);3 期 HCC、肿瘤切除标本中的血管浸润和 LT 后化疗与 HCC 复发相关(P=0.008、P<0.001 和 P<0.001)。HBV 再感染患者 HCC 复发的可能性是未发生 HBV 再感染患者的 3.6 倍。这些数据表明,如果 HBV 得到积极且成功的治疗,应进一步研究米兰标准以外的 HBV 和 HCC 患者进行 LT 的尝试。

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