修回日期: 2021-05-21
接受日期: 2021-06-02
在线出版日期: 2021-08-08
急性胰腺炎(acute pancreatitis, AP)是国内常见急腹症. 部分患者存在血清视黄醇结合蛋白(retinol-binding protein, RBP)降低的现象, 但其临床意义尚不明确.
探究RBP与AP严重程度和相关并发症的关系.
回顾性分析2018年入东部战区总医院的AP患者(发病7天内)的临床资料. 根据血清RBP水平将患者分为RBP正常组(normal retinol-binding protein, NRBP)和RBP降低组(low retinol-binding protein, LRBP), 比较两组基线特征、AP严重程度、临床预后等. 通过Logistic回归分析探究局部并发症的独立危险因素.绘制受试者工作曲线, 评估RBP对AP相关并发症的预测效能.
共纳入176例患者, 其中NRBP组41人、LRBP组135人. LRBP组AP严重程度显著高于NRBP组(轻症: 15.6%比39.0%, 中重症: 53.3%比29.3%, 重症: 31.1%比31.7%; P<0.05). LRBP组急性坏死组织积聚比例70.4%, 显著高于NRBP组的52.1%(P<0.05). 血清RBP水平在有局部并发症的患者中显著低于无局部并发症患者[24.00 (15.00, 27.50)mg/L比12.00 (9.00, 22.00)mg/L, P<0.05]. RBP预测局部并发症的曲线下面积值为0.708(95%CI: 0.615-0.801), 最佳截断点为15.5 mg/L, 灵敏度为60.4%, 特异性为75.7%. RBP降低是局部并发症的独立危险因素(OR = 5.306, P = 0.003, 95%CI: 1.771-15.896).
急性期血清RBP水平能较好的预测AP局部并发症的发生, 但与全身炎症反应和远隔脏器衰竭无显著相关性.
核心提要: 急性胰腺炎(acute pancreatitis, AP)患者血清视黄醇结合蛋白(retinol-binding protein, RBP)的降低是局部并发症的独立危险因素且与远隔脏器衰竭无显著相关性, 早期检测视黄醇结合蛋白对局部并发症有一定预测价值.
引文著录: 董小武, 魏梅, 马楠, 陆蓥蓥, 谢晓纯, 施笑蕾, 董杰, 马孝杰, 李百强, 童智慧, 李维勤. 循环视黄醇结合蛋白是急性胰腺炎局部并发症的独立危险因素. 世界华人消化杂志 2021; 29(15): 873-879
Revised: May 21, 2021
Accepted: June 2, 2021
Published online: August 8, 2021
Acute pancreatitis is a common acute abdomen in China. There is a decrease of serum retinol-binding protein (RBP) in some patients, but its clinical significance is not clear.
To explore the relationship between serum RBP and the severity and complications of AP.
The clinical data of AP patients admitted to Jinling Hospital in 2018 within 7 days of onset were analyzed retrospectively. The enrolled patients were divided into either a normal RBP (NRBP) group or a low RBP (LRBP) group according to the serum RBP level. The baseline characteristics, severity, and prognosis of disease were compared between the two groups. Logistic regression analysis was used to explore the independent risk factors for local complications. Receiver operating characteristic (ROC) curve was drawn to evaluate the performance of serum RBP in predicting complications.
A total of 176 patients were enrolled, including 41 in the NRBP group and 135 in the LRBP group. The severity of AP in the LRBP group was significantly more severe than that of the NRBP group (MAP: 15.6% vs 39.0%, MSAP: 53.3% vs 29.3%, SAP: 31.1% vs 31.7%; P < 0.05). The incidence of acute necrotic collection was 70.4% in the LRBP group, significantly higher than that (52.1%) of the NRBP group (P < 0.05). The serum level of RBP in patients with local complications was significantly lower than that in patients without (24.00 (15.00, 27.50) mg/L vs 12.00 (9.00, 22.00) mg/L, P < 0.05). The AUC of serum RBP for predicting local complications was 0.708 (95%CI: 0.615-0.801) and the cut-off value was 15.5 mg/L with a sensitivity 60.4% and specificity 75.7%. The decrease of serum RBP was an independent risk factor for local complications (OR = 5.306, P = 0.003, 95%CI: 1.771-15.896).
The level of serum RBP in the acute phase could predict the occurrence of local complications of AP, but has no significant correlation with systemic inflammatory response and remote organ failure.
- Citation: Dong XW, Wei M, Ma N, Lu YY, Xie XC, Shi XL, Dong J, Ma XJ, Li BQ, Tong ZH, Li WQ. Decreased circulating retinol binding protein is an independent risk factor for local complications of acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2021; 29(15): 873-879
- URL: https://www.wjgnet.com/1009-3079/full/v29/i15/873.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v29.i15.873
急性胰腺炎(acute pancreatitis, AP)是国内急腹症入院的主要原因[1]. AP严重程度的异质性较大, 多数轻症患者能在几天内恢复, 另外15-20%则进展为重症,发生局部和全身并发症, 死亡率显著增加, 可高达20%-40%[2]. AP的严重程度主要由局部并发症和器官功能衰竭决定[3]. 因此早期预测局部并发症和器官功能衰竭的发生, 评估AP严重程度, 对提高治疗的针对性和改善患者预后有重要作用.视黄醇结合蛋白(retinol-binding protein, RBP)是临床常见的检测指标.研究发现, AP患者存在血清RBP水平的降低[4]. 因此, 本研究回顾AP患者血清RBP水平, 探究其与AP严重程度和相关并发症的关系.
收集2018-01/2018-12间东部战区总医院(南京医科大学附属金陵医院)收治的AP患者. 纳入标准: (1)符合2012亚特兰大AP诊断标准的患者; (2)病程在7 d内的急性患者(以腹痛为起点). 排除标准: (1)年龄小于18周岁或大于75周岁的患者; (2)妊娠期或哺乳期妇女; (3)恶性肿瘤患者; (4)慢性胰腺炎或胰腺炎清创术后患者; (5)既往有慢性器官功能衰竭患者; (6)RBP数据缺失患者. 研究已通过本院急性胰腺炎数据管理委员会审核.
临床资料收集: (1)患者基线资料: 年龄、性别、体重指数(body mass index, BMI)、既往病史、病因、发病至入院时间、烟酒史等; (2)实验室检查资料; (3)患者病史包括疾病严重程度, 局部及全身并发症, 预后, 住院时间、住院费用等. 局部并发症和器官衰竭的诊断采用2012亚特兰大分型[3].
统计学处理 采用SPSS 24.0进行数据统计分析. 对满足正态分布的计量资料用平均数±标准差mean±SD表示, 根据方差是否齐, 采用t检验或近似t检验进行组间比较; 不符合正态分布的资料采用中位数(四分位数)[M (P25, P75)]表示, 用Mann-Whitney U检验进行组间比较. 计数资料采用χ2检验, 必要时, 采用Fisher精确检验. 采用二元Logistic回归分析进行单因素和多因素危险因素分析, 探讨RBP对局部并发症的独立影像作用. P<0.05认为差异有统计学意义.
本研究回顾了2018年入东部战区总医院急性胰腺炎治疗中心诊治的病程小于7 d的急性胰腺炎急性期患者, 经过筛选共入组176人(图1). 参考血清视黄醇结合蛋白的正常参考值25-70 mg/L, 176人分为RBP正常组(normal retinol-binding protein, NRBP) 41人, RBP降低组(low retinol-binding protein, LRBP)135人(图1). 两组患者在年龄、性别、BMI、饮酒史, 既往病史(高血压、糖尿病、高血脂)、病因等人口学和基线资料均无显著差异(表1). NRBP组既往吸烟患者比例显著高于LRBP组(46.3%比27.4%, P<0.05)(表1).
| NRBP(n = 41) | LRBP(n = 135) | 检验值 | P值 | |
| 年龄[岁, M (P25, P75)] | 37 (31.5, 45) | 42 (32, 52) | -1.259 | 0.208 |
| 性别(男, %) | 33 (80.5%) | 88 (65,2%) | 3.428 | 0.064 |
| BMI[kg/m2, M (P25, P75)] | 26.13 (23.80, 29.32) | 26.82 (24.42, 28.85) | -0.672 | 0.502 |
| 吸烟史(n, %) | 19 (46.3%) | 37 (27.4%) | 5.197 | 0.023 |
| 饮酒史(n, %) | 18 (43.9%) | 39 (28.9%) | 3.237 | 0.072 |
| 高血压(n, %) | 9 (22.0%) | 20 (14.8%) | 1.164 | 0.281 |
| 糖尿病(n, %) | 10 (24.4%) | 30 (22.2%) | 0.084 | 0.772 |
| 高脂血症(n, %) | 23 (56.1%) | 74 (54.4%) | 0.036 | 0.849 |
| 病因(n, %) | 1.134 | 0.769 | ||
| 胆源性 | 16 (39.0%) | 58 (43.0%) | ||
| 高甘油三酯血症性 | 23 (56.1%) | 71 (52.6%) | ||
| 酒精性 | 1 (2.4%) | 1 (0.7%) | ||
| 其他 | 1 (1%) | 5 (3.7%) |
根据2012改良亚特兰大分型(revised atlanta classification, RAC分型), NRBP组与LBRP组AP严重程度有显著差异(P<0.05)(表2). 两组中重症急性胰腺炎患者比例没有明显差异, 但LRBP组中重症急性胰腺炎(moderately severe acute pancreatitis, MSAP)患者比例显著高于NRBP组(53.3%比29.3%)(表2). LRBP组局部并发症急性坏死组织积聚的比例为70.4%高于NRBP组的52.1%, 差异有统计学意义(P<0.05)(表2). 两组在主要器官(肺、肾脏、循环)衰竭、脓毒症、死亡率、住院时长和住院费用方面没有显著差异(表2). LRBP组白细胞计数水平显著低于NRBP组[10.40 (7.61, 13.40)×109/L比11.40 (8.45, 14.70)×109/L, P<0.05], 但C反应蛋白(C-reactive Protein, CRP)显著高于NRBP组(175.93±7.18 mg/L比143.22±12.47 mg/L, P<0.05)(表2). 两组降钙素原(procalcitonin, PCT)水平没有显著差异. 以上提示RBP可能与AP局部并发症的发生有关, 而与远隔器官衰竭无明显相关性.
| NRBP(n = 41) | LRBP(n = 135) | 检验值 | P值 | |
| RAC分型(n, %) | 12.059 | 0.002 | ||
| MAP | 16 (39.0%) | 21 (15.6%) | ||
| MSAP | 12 (29.3%) | 72 (53.3%) | ||
| SAP | 13 (31.7%) | 42 (31.1%) | ||
| 局部并发症(n, %) | ||||
| 急性胰周液体积聚 | 4 (9.8%) | 19 (14.1%) | 0.516 | 0.472 |
| 急性坏死组织积聚 | 21 (51.2%) | 95 (70.4%) | 5.133 | 0.023 |
| 假性囊肿 | 0 | 0 | ||
| 包裹性坏死 | 0 | 0 | ||
| 器官衰竭(n, %) | ||||
| ARDS | 13 (31.7%) | 49 (36.3%) | 0.290 | 0.590 |
| AKI | 10 (24.4%) | 24 (17.8%) | 0.882 | 0.348 |
| Shock | 5 (12.2) | 12 (8.9%) | 0.394 | 0.550 |
| 脓毒症(n, %) | 3 (7.3%) | 8 (5.9) | 0.104 | 0.720 |
| WBC[×109/L, M (P25, P75)] | 11.40 (8.45, 14.70) | 10.40 (7.61, 13.40) | -2.011 | 0.044 |
| CRP (mg/L, mean±SD ) | 143.22±12.47 | 175.93±7.18 | -2.187 | 0.030 |
| PCT [μg/L, M (P25, P75)] | 0.49 (0.16, 3.66) | 0.52 (0.16, 1.75) | -0.580 | 0.562 |
| 死亡(n, %) | 1 (2.4%) | 8 (5.9%) | 0.788 | 0.687 |
| 住院时长[天, M (P25, P75)] | 5 (3.5, 17) | 7 (4, 11) | -0.481 | 0.631 |
| 总费用[万元, M (P25, P75)] | 3.40 (2.36, 16.49) | 3.69 (2.55, 8.21) | -0.131 | 0.896 |
根据患者是否发生局部并发症[胰周液体积聚、胰腺(周)组织坏死、假性囊肿、包裹性坏死], 将患者分为了无局部并发症组37人, 有局部并发症组139人. 有局部并发症组RBP显著低于无局部并发症组[12.00 (9.00, 22.00) mg/L比24.00 (15.00, 27.50) mg/L, P<0.05], CRP、PCT则显著高于后者(183.31±6.79 mg/L比115.81±12.23 mg/L, P<0.05; 0.65 (0.18, 3.42) μg/L 比0.29 (0.10, 0.75) μg/L, P<0.05)(表3). RBP对AP局部并发症的受试者工作特征曲线(receiver operating characteristic, ROC)如图2, 曲线下面积(area under curve, AUC)为0.708(95%CI: 0.615-0.801), 最佳截断点为15.5 mg/L, 约登指数为0.361, 灵敏度为60.4%, 特异性为75.7%.
| 无局部并发症(n = 37) | 有局部并发症(n = 139) | 检验值 | P值 | OR (95%CI) | P值 | |
| 年龄[岁, M (P25, P75)] | 44 (34.5, 51.5) | 40 (32, 50) | -1.286 | 0.198 | 0.983 (0.956, 1.011) | 0.228 |
| 性别(男, %) | 28 (75.7%) | 93 (66.9%) | 1.046 | 0.306 | 0.65 (0.283, 1.490) | 0.309 |
| BMI[kg/m2, M (P25, P75)] | 25.54 (23.36, 27.68) | 26.82 (24.56, 29.39) | -1.664 | 0.096 | 1.113 (0.984, 1.259) | 0.089 |
| 吸烟史(n, %) | 14 (37.8%) | 42 (30.2%) | 0.783 | 0.376 | 0.711 (0.334, 1.516) | 0.378 |
| 饮酒史(n, %) | 13 (35.1%) | 44 (31.7%) | 0.162 | 0.688 | 0.855 (0.398, 1.835) | 0.688 |
| 高血压(n, %) | 4 (10.8%) | 25 (18.0%) | 1.093 | 0.296 | 1.809 (0.588, 5.569) | 0.301 |
| 糖尿病(n, %) | 9 (24.3%) | 31 (22.3%) | 0.068 | 0.794 | 0.893 (0.381, 2.091) | 0.794 |
| 高脂血症(n, %) | 15 (40.5%) | 81 (58.3%) | 3.706 | 0.054 | 2.048 (0.979, 4.284) | 0.057 |
| 病因(n, %) | 4.959 | 0.173 | ||||
| 胆源性 | 18 (48.6%) | 56 (40.3%) | 3.111 (0.576, 16.795) | 0.187 | ||
| 高甘油三酯血症性 | 16 (43.2%) | 78 (56.1%) | 4.875 (0.901, 26.375) | 0.066 | ||
| 酒精性 | 0 | 2 (1.4%) | 1 | |||
| 特发性 | 3 (8.1%) | 3 (2.2%) | 1 | 0.265 | ||
| WBC[×109/L, M (P25, P75)] | 10.8 (8.38, 14.00) | 10.60 (7.80, 13.90) | -0.719 | 0.472 | 1.002 (0.937,1.072) | 0.951 |
| CRP (mg/L, mean±SD) | 115.81±12.23 | 183.31±6.79 | -4.687 | 0.000 | 1.011 (1.006, 1.016) | 0.000 |
| PCT[μg/L, M (P25, P75)] | 0.29 (0.10, 0.75) | 0.65 (0.18, 3.42) | -3.007 | 0.003 | 1.017 (0.965, 1.293) | 0.137 |
| RBP[mg/L, M (P25, P75)] | 24.00 (15.00, 27.50) | 12.00 (9.00, 22.00) | -3.881 | 0.000 | 0.935 (90.899, 0.972) | 0.001 |
| RBP降低(n, %) | 21 (56.8%) | 114 (82.0%) | 10.433 | 0.001 | 3.474 (1.591, 7.589) | 0.002 |
对两组患者进行单因素分析后(表3), 将可能危险因素RBP降低(以25 μg/mL为正常值下限)、CRP、PCT、BMI、高脂血症纳入多因素二元Logistic回归分析. 结果显示, RBP降低(OR = 5.306, P = 0.003, 95%CI: 1.771-15.896)和CRP(OR = 1.009, P = 0.019, 95%CI: 1.001-1.016)是AP患者发生局部并发症的独立危险因素(图3).
本研究回顾性分析了急性期AP患者的血清RBP水平, 发现RBP降低患者较正常患者病情更重, 前者MSAP比例为53.3%, 高于后者的29.3%. 其主要原因是RBP降低患者的局部并发症包括胰周液体积聚和胰腺(周)坏死组织积聚的发生率更高. 再对急性期患者局部并发症进行危险因素分析后进一步明确了RBP降低是发生局部并发症的独立危险因素.
AP严重程度的两个主要决定性因素是局部并发症和器官功能衰竭[3]. AP患者中约有20%的患者会发生胰腺(周)组织坏死[5]. 局部并发症也是全身器官功能衰竭的重要原因. 在AP的发病过程中胰腺腺泡细胞内促炎通路如NF-κB等上调, 促进炎症因子表达, 引起全身炎症反应[6]. 另一方面, 坏死的腺泡细胞释放大量DAMPs, 包括HMGB1, DNA等, 进一步激活全身炎症反应, 并导致远隔器官损伤[7]. 因此早期对局部并发症进行诊断和预测对患者的转归有重要作用. CT是临床常用的诊断AP局部并发症和严重程度的检查手段[8,9]. 血清RBP检测是临床常见生化检测, 相比于CT较长的检查间隔以及较高的费用, 更为简便易行, 且能进行长期动态检测, 及早发现病情变化.
RBP是血液中转运维生素的蛋白, 常被用作营养状态的指标[10]. 在许多胰腺疾病中均发现RBP的降低, 包括急性胰腺炎、慢性胰腺炎、胰腺癌、胰腺外分泌功能不全[4,10-12]. Luo等[4]回顾分析了AP患者和慢性胰腺炎急性加重的患者, 发现白细胞和RBP的比率能很好的区分两类患者. 这些均提示RBP在胰腺生理和病理生理过程中起重要作用, 而其变化也对胰腺疾病也有一定提示作用. 但具体机制和表现形式仍需进一步研究. 本研究中LRBP组病情更重, CRP高水平与病情严重程度一致. 但LRBP组WBC显著低于NRBP组. 有文献报道急性髓细胞性白血病患者RBP降低[13], 提示RBP可能参与白细胞的形成, 但目前尚无具体机制的研究. LRBP组WBC的降低可能与RBP的降低有关, 也可能是样本量较少导致的选择偏倚.
本研究尚存在以下不足: 对NRBP组与LRBP组分析中, 两组基线水平并不完全一致, NRBP组患者吸烟比例显著高于LNRP组, 饮酒比例数值上也更高, 可能原因是NRBP组男性比例数值上更高. 虽然吸烟和饮酒是AP的危险因素[14], 但是NRBP组病情更轻, 两者可能不是影响预后的主要因素. Gao等人[15]在对136例健康男性的研究中发现, 吸烟者的RBP4(RBP家族成员之一)的水平更高, 而另外两项临床研究未发现饮酒对血清RBP水平的影响[16,17]. NRBP组更高的吸烟率可能对结果有一定影响. 此外, 本研究为单中心回顾性研究, 由于本中心主要收治重症急性胰腺炎患者, 中重症及重症患者数量远多于轻症患者, 与流行病学数据不符, 存在一定选择偏倚; 未对血清RBP水平进行动态观察及分析. 因此, 还需要进一步的多中心大样本的研究, 以明确RBP在AP临床诊疗中的作用.
综上所述, AP早期RBP的降低与AP局部并发症独立相关, 能较好的预测局部并发症的发生. 但与全身炎症反应和远隔脏器衰竭无显著相关性.
急性胰腺炎(acute pancreatitis, AP)是临床常见急腹症, 患者病情差异较大, 早期识别重症患者对指导临床治疗有重要意义. 临床上部分急性胰腺炎患者存在血清视黄醇结合蛋白(retinol-binding protein, RBP)水平降低的现象, 但对于其临床意义尚无研究.
总结血清视黄醇结合蛋白降低的急性胰腺炎患者的特征, 发现其临床价值.
探究视黄醇结合蛋白与急性胰腺炎严重程度和相关并发症的关系.
回顾分析了2018年本院收治的急性期急性胰腺炎患者的临床数据, 比较了视黄醇结合蛋白正常与降低患者基线特征、病情严重程度和预后等的差异. 并通过单因素和多因素分析探究视黄醇结合蛋白和局部并发症的相关性.
结果显示视黄醇结合蛋白降低患者病情更重, 局部并发症发生率更高. 视黄醇结合蛋白降低是局部并发症的独立危险因素.
急性胰腺炎患者早期视黄醇结合蛋白降低是局部并发症的独立危险因素, 有良好的预测价值.
本研究为单中心回顾性研究, 样本量有限, 需多中心、大样本研究来进一步验证本研究结果. 未来可探究早期视黄醇结合蛋白动态变化对急性胰腺炎严重程度和相关并发症的关系.
学科分类: 胃肠病学和肝病学
手稿来源地: 江苏省
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