Lau George K K, Leung Yu-hung, Fong Daniel Y T, Au Wing-yan, Kwong Yok-lam, Lie Albert, Hou Ji-lin, Wen Yu-mei, Nanj Amin, Liang Raymond
Division of Gastroenterology and Hepatology, University Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, People's Republic of China.
Blood. 2002 Apr 1;99(7):2324-30. doi: 10.1182/blood.v99.7.2324.
The risk factors for hepatitis due to hepatitis B virus (HBV) reactivation in patients positive for hepatitis B surface antigen (HBsAg) treated with autologous hematopoietic cell transplantation (HCT) are unknown. We evaluated 137 consecutive patients (23 positive for HBsAg, 37 positive for hepatitis B surface antibody, and 77 negative for HBV) who underwent HCT. Serial serum ALT were measured before transplant and after transplant at 1 to 4 weekly intervals for the first year and then at 2 to 12 weekly intervals thereafter. Before HCT, basic core promoter (T(1762)/A(1764)) and precore (A(1896)) HBV variants were determined in HBsAg-positive and HBV DNA-positive (by polymerase chain reaction assay) patients by direct sequencing and serum HBV DNA quantitation using the Digene Hybrid Capture II assay. Cox proportional hazards analysis was used to assess the association between pretransplantation HBV virologic and host factors and occurrence of hepatitis due to HBV reactivation. After HCT, hepatitis due to HBV reactivation was more common in HBsAg-positive patients than in HBsAg-negative patients (hazard ratio, 33.3; 95% confidence interval [CI], 7.35-142.86; P <.0001). HBsAg-positive patients with detectable serum HBV DNA before HCT (on Digene assay) had a significantly higher risk of hepatitis due to HBV reactivation than HBsAg-positive patients with no detectable serum HBV DNA (adjusted hazard ratio, 9.35; 95% CI, 1.65-52.6; P =.012). Thus, we found that hepatitis due to HBV reactivation is common in HBsAg-positive patients undergoing autologous HCT. A high HBV DNA level (>10(5) copies/mL) was the most important risk factor for HBV reactivation, and its lowering by administration of nucleoside analogues before transplantation should be considered.
接受自体造血细胞移植(HCT)治疗的乙肝表面抗原(HBsAg)阳性患者中,因乙肝病毒(HBV)再激活导致肝炎的危险因素尚不清楚。我们评估了137例连续接受HCT的患者(23例HBsAg阳性,37例乙肝表面抗体阳性,77例HBV阴性)。在移植前及移植后,第一年每周1至4次测定血清ALT,之后每2至12周测定一次。在HCT前,通过直接测序和使用Digene Hybrid Capture II检测法进行血清HBV DNA定量,对HBsAg阳性且HBV DNA阳性(通过聚合酶链反应检测)的患者测定基本核心启动子(T(1762)/A(1764))和前核心(A(1896))HBV变异体。采用Cox比例风险分析评估移植前HBV病毒学和宿主因素与HBV再激活所致肝炎发生之间的关联。HCT后,HBsAg阳性患者中因HBV再激活导致的肝炎比HBsAg阴性患者更常见(风险比,33.3;95%置信区间[CI],7.35 - 142.86;P <.0001)。HCT前血清HBV DNA可检测到(Digene检测法)的HBsAg阳性患者,因HBV再激活导致肝炎的风险显著高于血清HBV DNA检测不到的HBsAg阳性患者(校正风险比,9.35;95% CI,1.65 - 52.6;P =.012)。因此,我们发现接受自体HCT的HBsAg阳性患者中,因HBV再激活导致的肝炎很常见。高HBV DNA水平(>10(5)拷贝/mL)是HBV再激活的最重要危险因素,移植前给予核苷类似物降低其水平值得考虑。