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摘要：
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摘要：目的 探讨微小RNA（microRNA，miRNA）-30a mRNA与miR-196b mRNA在慢性乙型肝炎
（chronic hepatitis B，CHB）肝纤维化患者血清中的相对表达量及临床意义。方法 选取2016年1月至
2018年12月在江苏省张家港市第一人民医院行经皮肝组织活检确诊为CHB肝纤维化的139例患者为
CHB肝纤维化组，选取130例同期健康体检者为对照组。对CHB肝纤维化患者进行肝组织病理学检
查。采用Au480全自动生化分析仪检测血清天门冬氨酸氨基移酶（aspartate transferase，AST）、丙氨
酸氨基转移酶（alanine transaminase，ALT）及白蛋白水平；采用酶联免疫吸附试验（enzyme-linked
immunosorbent assay，ELISA）检测血清中金属蛋白酶-1抑制剂（metalloproteinase tissue inhibitor-1，
TIMP-1）浓度；采用荧光定量聚合酶链反应检测miR-30a和miR-196b mRNA相对表达量，计算FIB-4
指数。对CHB肝纤维化患者进行肝组织病理学检查确定肝纤维化分期。采用Pearson法分析miR-30a
mRNA和miR-196b mRNA相对表达量及其与各临床指标的相关性；采用受试者工作特征（receiver
operator characteristic，ROC）曲线评价miR-30a和miR-196b对肝纤维化的诊断价值。结果 与对照组
相比，CHB肝纤维化患者组血清中ALT [（65.34 ± 13.53）U/L vs（18.28 ± 3.14）U/L]、AST [（52.84 ±
14.02）U/L vs（25.84 ± 1.26）U/L]、TIMP-1 [（183.98 ± 42.07）ng/ml vs（80.59 ± 13.09）ng/ml]和FIB-4
指数（1.33 ± 0.09 vs 0.78 ± 0.06）显著升高，miR-30a mRNA相对表达量（0.60 ± 0.08 vs 1.00 ± 0.09）
和miR-196b mRNA相对表达量（0.45 ± 0.04 vs 1.00 ± 0.02）显著降低，差异均有统计学意义（P均＜
0.05）。139例患者中S0～S1期占32.37%（45/139），S2～S3期占45.32%（63/139），S4期占22.31%
（31/139）。S0～S1期患者miR-30a mRNA相对表达量、miR-196b mRNA相对表达量、TIMP-1和
FIB-4指数分别为0.83 ± 0.06、0.76 ± 0.05、（142.68 ± 13.21）ng/ml、0.84 ± 0.08，S2～S3期患者上述
指标分别为0.69 ± 0.06、0.41 ± 0.08、（257.50 ± 53.05）ng/ml、1.23 ± 0.09，S4期患者上述指标分别
0.28 ± 0.02、0.21 ± 0.05、（383.52 ± 62.31）ng/ml、2.48 ± 0.19，血清中miR-30a mRNA相对表达量
和miR-196b mRNA相对表达量随纤维化分期的增加而降低，TIMP-1和FIB-4指数随肝纤维化分期的增
加而增加（P均＜ 0.05）。CHB肝纤维化患者血清miR-30a和miR-196b与TIMP-1、FIB-4和肝纤维化
分期呈负相关（P ＜ 0.05），与ALT和AST无相关性（P ＞ 0.05）。miR-30a mRNA相对表达量、miR-
196b mRNA相对表达量、TIMP-1和FIB-4指数诊断CHB肝纤维化患者肝纤维化的ROC曲线下面积（area
under ROC curve，AUC）分别为0.847（95%CI：0.756～0.928）、0.942（95%CI：0.860～0.983）、0.792
（95%CI：0.721～0.855）、0.895（95%CI：0.821～0.967），miR-196b mRNA相对表达量的AUC显著高
于其他指标（P均＜ 0.001）。以0.468作为临界值，miR-196b mRNA相对表达量诊断的灵敏度和特异度
分别为89.45%和83.60%。结论 CHB肝纤维化患者血清中miR-30a mRNA和miR-196ba mRNA相对表达量
降低，检测miR-30a和miR-196ba mRNA相对表达量有助于评估CHB肝纤维化患者的肝纤维化程度。
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Abstract: Objective To investigate the serum relative expression and clinical significance of microRNA-
30a (miR-30a) mRNA and miR-196ba mRNA in chronic hepatitis B (CHB) patients complicated with liver
fibrosis. Methods Total of 139 patients with CHB and liver fibrosis diagnosed by percutaneous liver
biopsy in Zhangjiagang First People’s Hospital from January 2016 to December 2018 were selected as
CHB liver fibrosis group, and 130 healthy subjects in the same period were selected as control group.
Liver histopathology was performed in CHB patients with liver fibrosis. Serum aspartate aminotransferase
(AST), alanine aminotransferase (ALT) and albumin levels were detected by Au480 automatic biochemical
analyzer, and serum metalloproteinase tissue inhibitor-1 (TIMP-1) was detected by enzyme-linked
immunosorbent assay (ELISA). The relative expression of miR-30a and miR-196b mRNA was detected by
fluorescence quantitative polymerase chain reaction, and FIB-4 index was calculated. Liver histopathology
was performed in patients with CHB and liver fibrosis to determine the stage of liver fibrosis. Pearson
method was used to analyze the correlation between the relative expression of miR-30a mRNA and miR-
196b mRNA and clinical indicators. Receiver operator characteristic (ROC) curve was used to evaluate the
diagnostic value of miR-30a and miR-196b for liver fibrosis. Results Compared with control group, serum
ALT [(65.34 (65.34 ± 13.53) U/L vs (18.28 ± 3.14) U/L], AST [(52.84 ± 14.02) U/L vs (25.84 ± 1.26) U/L], TIMP-1
[(183.98 ± 42.07) ng/ml vs (80.59 ± 13.09) ng/ml] and FIB-4 index (1.33 ± 0.09 vs 0.78 ± 0.06) of patients
in CHB and liver fibrosis group increased, the relative expression of miR-30a mRNA (0.60 ± 0.08 vs 1.00 ±
0.09) and the relative expression of miR-196b mRNA (0.45 ± 0.04 vs 1.00 ± 0.02) decreased, the differences
were statistically significant (all P ＜ 0.05). Of the 139 patients, S0～S1 stage accounted for 32.37%
(45/139), S2～S3 stage accounted for 45.32% (63/139) and S4 stage accounted for 22.31% (31/139). Relative
expression of miR-30a mRNA, relative expression of miR-196b mRNA, TIMP-1 and FIB-4 index of patients
with S0～S1 stage were 0.83 ± 0.06, 0.76 ± 0.05, (142.68 ± 13.21) ng/ml and 0.84 ± 0.08, respectively. The
above indexes of patients with S2～S3 stage were 0.69 ± 0.06, 0.41 ± 0.08, (257.50 ± 53.05) ng/ml
and 1.23 ± 0.09, respectively and 0.28 ± 0.02, 0.21 ± 0.05, (383.52 ± 62.31) ng/ml and 2.48 ± 0.19 of patients
with S4 stage, respectively. Relative expression of serum miR-30a mRNA and miR-196b mRNA decreased
with the increase of fibrosis stage, while TIMP-1 and FIB-4 index increased with the increase of fibrosis
stage (P ＜ 0.05). Serum levels of miR-30a and miR-196b in CHB patients with liver fibrosis were negatively
correlated with TIMP-1, FIB-4 index and liver fibrosis stage (P ＜ 0.05), which had no correlation with ALT
and AST (P ＞ 0.05). The area under the ROC curve (AUC) of the relative expression of miR-30a mRNA, the
relative expression of miR-196b mRNA, TIMP-1 and FIB-4 index for the diagnosis of liver fibrosis in CHB
patients were 0.847 (95%CI: 0.756～0.928), 0.942 (95%CI: 0.860～0.983), 0.792 (95%CI: 0.721～0.855),
0.895 (95%CI: 0.821～0.967) and 0.895 (95%CI: 0.821～0.967), respectively. The AUC of relative expression of
miR-196b mRNA was significantly higher than that of other indicators (all P ＜ 0.001). With 0.468 as the cut-off
value, the sensitivity and specificity of the relative expression of miR-196b mRNA were 89.45% and 83.60%,
respectively. Conclusions The serum relative expression of miR-30a mRNA and miR-196b in CHB patients
with liver fibrosis decreased. The detection of relative miR-30a mRNA and miR-196ba mRNA is helpful to
assessing the degree of liver fibrosis in CHB patients with liver fibrosis.
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