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CD163 表达增加与乙型肝炎慢加急性肝衰竭相关。

Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure.

机构信息

Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China.

出版信息

World J Gastroenterol. 2013 May 14;19(18):2818-25. doi: 10.3748/wjg.v19.i18.2818.

Abstract

AIM

To assess CD163 expression in plasma and peripheral blood and analyze its association with disease in acute-on-chronic hepatitis B liver failure (ACHBLF) patients.

METHODS

A retrospective study was conducted from January 1, 2011 to January 1, 2012. Forty patients with ACHBLF (mean age 44.48 ± 12.28 years, range 18-69 years), 40 patients with chronic hepatitis B (CHB) (mean age 39.45 ± 12.22 years, range 21-57 years) and 20 age- and sex-matched healthy controls (mean age 38.35 ± 11.97 years, range 28-60 years) were included in this study. Flow cytometry was used to analyze the frequency of CD163+ peripheral blood mononuclear cells (PBMCs) and surface protein expression of CD163. Real-time transcription-polymerase chain reaction was performed to assess relative CD163 mRNA levels in PBMCs. Plasma soluble CD163 (sCD163) levels were measured by enzyme-linked immunosorbent assay. Clinical variables were also recorded. Comparisons between groups were analyzed by Kruskal-Wallis H test and Mann-Whitney U test. Statistical analyses were performed using SPSS 15.0 software and a P value < 0.05 was considered statistically significant.

RESULTS

Flow cytometry showed that the population of CD163+ PBMCs was significantly greater in ACHBLF patients than in CHB patients and healthy controls (47.9645% ± 17.1542%, 32.0975% ± 11.0215% vs 17.9460% ± 6.3618%, P < 0.0001). However, there were no significant differences in mean fluorescence intensity of CD163+ PBMCs within the three groups (27.4975 ± 11.3731, 25.8140 ± 10.0649 vs 20.5050 ± 6.2437, P = 0.0514). CD163 mRNA expression in ACHBLF patients was significantly increased compared with CHB patients and healthy controls (1.41 × 10⁻² ± 2.18 × 10⁻², 5.10 × 10⁻³ ± 3.61 × 10⁻³ vs 37.0 × 10⁻⁴ ± 3.55 × 10⁻⁴, P = 0.02). Plasma sCD163 levels in patients with ACHBLF were significantly increased compared with CHB patients and healthy controls (4706.2175 ± 1681.1096 ng/mL, 1089.7160 ± 736.8395 ng/mL vs 435.9562 ± 440.8329 ng/mL, P < 0.0001). In ACHBLF patients, plasma sCD163 levels were significantly positively associated with model for end-stage liver disease scores (r = 0.5075, P = 0.008), hepatitis B virus-DNA (r = 0.6827, P < 0.0001), and negatively associated with prothrombin activity (r = -0.3348, P = 0.0347), but had no correlation with total bilirubin (r = 0.2551, P = 0.1122). Furthermore, sCD163 was obviously elevated in non-surviving patients compared with surviving patients with ACHBLF (5344.9080 ± 1589.5199 ng/mL vs 3641.7333 ± 1264.5228 ng/mL, P = 0.0321).

CONCLUSION

CD163 and sCD163 may be related to disease severity and prognosis in ACHBLF patients.

摘要

目的

评估 CD163 在血浆和外周血中的表达,并分析其与急性慢加亚急性乙型肝炎肝衰竭(ACHBLF)患者疾病的关系。

方法

这是一项回顾性研究,时间为 2011 年 1 月 1 日至 2012 年 1 月 1 日。纳入 40 例 ACHBLF 患者(平均年龄 44.48 ± 12.28 岁,范围 18-69 岁)、40 例慢性乙型肝炎(CHB)患者(平均年龄 39.45 ± 12.22 岁,范围 21-57 岁)和 20 例年龄和性别匹配的健康对照者(平均年龄 38.35 ± 11.97 岁,范围 28-60 岁)。采用流式细胞术分析 CD163+外周血单个核细胞(PBMCs)的频率和 CD163 的表面蛋白表达。采用实时转录-聚合酶链反应检测 PBMCs 中相对 CD163 mRNA 水平。采用酶联免疫吸附试验测定血浆可溶性 CD163(sCD163)水平。记录临床变量。采用 Kruskal-Wallis H 检验和 Mann-Whitney U 检验进行组间比较。采用 SPSS 15.0 软件进行统计学分析,P 值<0.05 为差异有统计学意义。

结果

流式细胞术显示,ACHBLF 患者 CD163+PBMCs 群体显著高于 CHB 患者和健康对照者(47.9645%±17.1542%、32.0975%±11.0215% vs 17.9460%±6.3618%,P<0.0001)。然而,三组之间 CD163+PBMCs 的平均荧光强度无显著差异(27.4975±11.3731、25.8140±10.0649 vs 20.5050±6.2437,P=0.0514)。ACHBLF 患者的 CD163 mRNA 表达明显高于 CHB 患者和健康对照者(1.41×10⁻²±2.18×10⁻²、5.10×10⁻³±3.61×10⁻³ vs 37.0×10⁻⁴±3.55×10⁻⁴,P=0.02)。ACHBLF 患者的血浆 sCD163 水平明显高于 CHB 患者和健康对照者(4706.2175±1681.1096 ng/mL、1089.7160±736.8395 ng/mL vs 435.9562±440.8329 ng/mL,P<0.0001)。在 ACHBLF 患者中,血浆 sCD163 水平与终末期肝病模型评分(r=0.5075,P=0.008)、乙型肝炎病毒-DNA(r=0.6827,P<0.0001)显著正相关,与凝血酶原活性(r=-0.3348,P=0.0347)显著负相关,与总胆红素无相关性(r=0.2551,P=0.1122)。此外,ACHBLF 非存活患者的 sCD163 明显高于存活患者(5344.9080±1589.5199 ng/mL vs 3641.7333±1264.5228 ng/mL,P=0.0321)。

结论

CD163 和 sCD163 可能与 ACHBLF 患者的疾病严重程度和预后相关。

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