摘要:
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摘要:目的 探讨酒精性肝炎患者自噬相关蛋白表达水平辅助肝纤维化程度诊断的临床
价值。方法 以钟祥市人民医院2019年2月至2021年9月收治的97例酒精性肝炎患者为研
究对象,根据患者肝纤维化程度将分为S0期(24例)、S1期(31例)、S2期(17例)、
S3期(15例)、S4期(10例),分析患者自噬相关蛋白 [p62、微管相关蛋白1轻链3-Ⅱ
(microtubule-associated protein 1 light chain 3-Ⅱ,LC3-Ⅱ)、Beclin1] 的表达水平。采用
Spearman相关分析酒精性肝炎患者血清p62、LC3-Ⅱ、Beclin1水平与肝纤维化分期的相关
性。采用受试者工作特征(receiver operator characteristic,ROC)曲线分析自噬相关蛋白
对患者肝纤维化程度的评估价值。采用Logistic回归分析自噬相关蛋白是否为患者显著肝
纤维化(S3~S4期)的影响因素。结果 肝纤维化S0期、S1期、S2期、S3期、S4期酒精性
肝炎患者血清p62水平分别为(4.31 ± 0.74)μg/L、(3.43 ± 0.65)μg/L、(3.02 ± 0.57)μg/L、
(2.57 ± 0.41)μg/L、(2.19 ± 0.43)μg/L;LC3-Ⅱ水平分别为(36.75 ± 7.92)μg/L、
(51.52 ± 8.74)μg/L、(55.79 ± 7.30)μg/L、(59.91 ± 8.12)μg/L、(67.05 ±
9.37)μg/L;Beclin1水平分别为(8.93 ± 1.24)μg/L、(10.04 ± 1.82)μg/L、
(10.85 ± 1.03)μg/L、(11.52 ± 1.10)μg/L、(12.37 ± 1.86)μg/L;组间各指标
差异均有统计学意义(F值分别为30.865、32.922、13.449,P均< 0.001),p62
随肝纤维化分期的升高呈下降趋势,LC3-Ⅱ和Beclin1水平随肝纤维化分期的升高
呈上升趋势。Spearman相关性分析表明,p62水平与肝纤维化分期呈负相关(rs =
-0.765,P < 0.001),LC3-Ⅱ、Beclin1与肝纤维化分期呈正相关(rs = 0.751,P <
0.001;rs = 0.615,P < 0.001)。p62、LC3-Ⅱ、Beclin1及三者联合检测评估患者肝
纤维化程度的ROC曲线下面积分别为0.910、0.853、0.825、0.964,三者联合检测的
ROC曲线下面积显著高于各指标单独检测(Z值分别为2.328、2.806、3.148,P值分别
为0.020、0.005、0.002)。Logistic回归分析表明LC3-Ⅱ ≥ 57.37 μg/L(OR = 15.872,
95%CI:2.310~109.077,P = 0.005)、Beclin1 ≥ 10.88 μg/L(OR = 72.347,95%CI:
5.344~979.413,P = 0.001)为患者发生显著肝纤维化的危险因素,p62 ≥ 2.61 μg/L为
保护因素(OR = 0.013,95%CI:0.001~0.130,P < 0.001)。结论 酒精性肝炎患者
p62、LC3-Ⅱ、Beclin1水平与肝纤维化分期相关,且联合检测对显著肝纤维化的评估价
值较高。
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Abstract: Objective To investigate the clinical value of expression levels of autophagy-
related proteins in adjuvant diagnosis of liver fibrosis degree in patients with alcoholic
hepatitis. Methods Total of 97 patients with alcoholic hepatitis in Zhongxiang People’s
Hospital from February 2019 to September 2021 were selected as the research subjects.
According to the degree of liver fibrosis, the patients were divided into fibrosis stages S0
(24 cases), S1 (31 cases), S2 (17 cases), S3 (15 cases) and S4 (10 cases). The expression
levels of autophagy-related proteins [including p62, microtubule-associated protein 1 light
chain 3-Ⅱ (LC3-Ⅱ) and Beclin1] were analyzed. Spearman correlation analysis was used
to analyze the correlation of serum p62, LC3-Ⅱ, Beclin1 levels and liver fibrosis staging in
patients with alcoholic hepatitis. The receiver operator characteristic (ROC) curve was used
to analyze the evaluation value of autophagy-related proteins on the degree of liver fibrosis.
Logistic regression analysis was used to determine whether autophagy-related proteins were
influencing factors of liver fibrosis (S3~S4 stage) in patients with alcoholic hepatitis. Results
The serum p62 levels of patients with alcoholic hepatitis in liver fibrosis stages S0, S1, S2,
S3, and S4 were (4.31 ± 0.74) μg/L, (3.43 ± 0.65) μg/L, (3.02 ± 0.57) μg/L, (2.57 ± 0.41) μg/L
and (2.19 ± 0.43) μg/L, respectively, the levels of LC3-Ⅱ were (36.75 ± 7.92) μg/L, (51.52 ±
8.74) μg/L, (55.79 ± 7.30) μg/L, (59.91 ± 8.12) μg/L and (67.05 ± 9.37) μg/L, respectively,
and the levels of Beclin1 were (8.93 ± 1.24) μg/L, (10.04 ± 1.82) μg/L, (10.85 ± 1.03) μg/L,
(11.52 ± 1.10) μg/L and (12.37 ± 1.86) μg/L, respectively, the differences were statistically
significant (F = 30.865, 32.922, 13.449, all P < 0.001). The level of p62 showed a decreasing
trend with the increase of liver fibrosis staging while LC3-Ⅱ and Beclin1 levels showed increasing
trends with the increase of liver fibrosis staging. Spearman correlation analysis showed that p62
level was negatively correlated with liver fibrosis staging (rs = -0.765, P < 0.001), and LC3-Ⅱ
and Beclin1 were positively correlated with liver fibrosis staging (rs = 0.751, P < 0.001; rs =
0.615, P < 0.001). The areas under the ROC curve of p62, LC3-Ⅱ, Beclin1 and combined
detection of the three indicators in assessing the degree of liver fibrosis were 0.910, 0.853,
0.825 and 0.964, and the area under the ROC curve of combined detection was significantly
higher than that of single detection (Z = 2.328, 2.806, 3.148, P = 0.020, 0.005, 0.002). Logistic
regression analysis showed that LC3-Ⅱ ≥ 57.37 μg/L (OR = 15.872, 95%CI: 2.310~109.077,
P = 0.005) and Beclin1 ≥ 10.88 μg/L (OR = 72.347, 95%CI: 5.344~979.413, P = 0.001)
were risk factors for significant liver fibrosis, and p62 ≥ 2.61 μg/L was a protective factor
(OR = 0.013, 95%CI: 0.001~0.130, P < 0.001). Conclusions The levels of p62, LC3-Ⅱ and
Beclin1 of patients with alcoholic hepatitis were related to liver fibrosis staging, and combined
detection had a good evaluated value on the degree of liver fibrosis.
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