【摘要】 目的 探讨慢性乙型肝炎(CHB)患者血清中IL-33水平与肝纤维化病情严重程度的关系。方法 选择2017年6月—2019年12月本院感染科收治的105例CHB患者(CHB组)和40名健康体检者(对照组)作为研究对象。CHB患者肝纤维化严重程度采用Metavir评分系统分期，其中F0期、F1-F3期和F4期分别表示无肝纤维化、肝纤维化及肝硬化。检测并比较两组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(IV-C)、透明质酸(HA)、层黏蛋白(LN)及IL-33水平的差异。分析F0期、F1-F3期和F4期血清IL-33水平的差异及血清IL-33与PCIII、IV-C、HA及LN的相关性。血清IL-33水平诊断肝纤维化及肝硬化的临床效能采用ROC曲线分析。结果 与对照组相比，CHB组血清ALT[(374.15±38.27)U/L vs.(31.08±6.47)U/L,t=56.273,P<0.000]、AST[(370.09±40.28)U/L vs.(34.28±5.33)U/L,P<0.000]、TBIL[(32.28±4.16)μmol/L vs.(11.07±3.62)μmol/L,P<0.000)]、PCIII[(56.28±8.11)μg/L vs.(15.39±4.02)μg/L,P<0.000)]、IV-C[(255.41±35.68)μg/L vs.(100.28±24.19)μg/L,P<0.000)]、HA[(200.17±30.53)μg/L vs.(80.16±11.79)μg/L,P<0.000)]、LN[(274.87±22.43)μg/L vs.(159.43±16.06)μg/L,P<0.000])和IL-33[(602.14±46.57)pg/ml vs.(184.07±20.45)pg/ml,P<0.000)]水平均显著升高。F0期、F1-F3期和F4期三组血清PCIII、IV-C、HA、LN和IL-33水平相比较存在显著差异(F=34.448,F=29.115,F=18.554,F=23.367,F=42.814,均P<0.000);与F0期和F1-F3期相比，F4期血清PCIII、IV-C、HA、LN和IL-33水平显著升高，与F0期相比，F1-F3期血清PCIII、IV-C、HA、LN和IL-33水平显著升高，差异具有统计学意义(P<0.000)。相关性分析结果显示，血清IL-33水平与PCIII、IV-C和LN均呈现显著正相关性，相关系数r分别为0.412,0.357,0.371,均P<0.05,而与HA无明显相关性，相关系数r为0.145,P=0.235。ROC曲线结果显示血清IL-33水平在诊断CHB患者发生肝纤维化的AUC为0.896(95%CI:0.769-0.942),当截断值为648.59 pg/ml时，敏感度和特异度分别为92.51%和86.94%;血清IL-33水平在诊断CHB患者发生肝硬化的AUC为0.798(95%CI:0.753-0.854),当截断值为769.59 pg/ml时，敏感度和特异度分别为85.48%和82.07%。结论 IL-33与CHB患者肝纤维化的严重程度密切相关，可作为CHB患者发生肝纤维化的一项血清学标志物。更多还原

【Abstract】 Objective To investigate the relationship between serum IL-33 level and severity of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A total of 105 patients suffered with CHB(CHB group) those were admitted to the department of infectious diseases, the first affiliated hospital of Xinxiang Medical University between June 2017 and December 2019 and 40 healthy people(control group) were collected as study objects. The severity of liver fibrosis in patients with CHB was evaluated by Metavir scores system and stage of F0, F1-F3 and F4 were represented no liver fibrosis, liver fibrosis and cirrhosis, respectively. The serum level of Alamine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), Type III precollagen(PCIII), Type IV collagen(IV-C), hyaluronic acid(HA), laminin(LN) and IL-33 were detected and compared between the two groups. The serum level of IL-33 in F0 stage, F1-F3 stage and F4 stage was also compared. The relationship between IL-33 and PCIII, IV-C, HA, LN level were analyzed by Spearman test. The clinical value of IL-33 in the diagnosis of liver fibrosis and cirrhosis in patients with CHB was analyzed by using ROC curve.Results The serum level of ALT [(374.15±38.27) vs.(31.08±6.47), t=56.273, P<0.000],AST [( 370.09±40.28) vs.( 34.28± 5. 33),t = 52. 441,P < 0. 000],TBIL [( 32. 28 ± 4. 16) vs.( 11. 07 ± 3. 62),t = 28.396,P<0.0000,PCIII [( 56.28± 8. 11) vs.( 15. 39 ± 4. 02),t = 30. 447,P < 0. 000],IV-C [( 255. 41 ±35.68) vs.( 100.28±24.19),t = 25.341,P< 0.000],HA [( 200.17 ± 30.53) vs.( 80.16 ± 11.79),t = 24.142,P<0.000],LN [( 274.87±22.43) vs.( 159.43±16.06),t = 29.746,P<0.000]and IL-33 [( 602.14±46.57) vs.( 184.07±20.45),t = 54.711,P< 0.000] in CHB group were significantly higher than those of control group.There were significant differences in serum levels of PCIII,IV-C,HA,LN and IL-33 among F0,F1-F3 and F4stage( F = 34.448,F = 29.115,F = 18.554,F = 23.367,F = 42.814,all P< 0.000). The serum level of PCIII,IV-C,HA,LN and IL-33 in F4 stage were significantly higher than those in F0 and F1-F3 stage,and the levels of the above five indexes in F1-F3 stage were significantly higher than those in F0 stage( P<0.000). There was a significant positive correlation between the serum IL-33 levels and PCIII,IV-C,and LN,and the correlation coefficient r were 0.412,0.357 and 0.371,respectively,all P< 0.05,while there was no significant correlation between serum IL-33 and HA,and the correlation coefficient r was 0.145,P = 0.235. The ROC results showed that the AUC of serum IL-33 in the diagnose of liver fibrosis in patients with CHB was 0.896( 95% CI: 0.769-0.942),when the cut-off value was 648. 59 pg/ml,the sensitivity and specificity were 92. 51% and 86. 94%,respectively. The AUC of serum IL-33 in the diagnose of cirrhosis in patients with CHB was 0. 798( 95% CI:0.753-0.854),when the cut-off value was 769. 59 pg/ml,the sensitivity and specificity were 85. 48% and82.07%,respectively.Conclusions IL-33 is significant related to the severity of liver fibrosis in patients with CHB and IL-33 might be used as a serological marker of liver fibrosis.更多还原