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GGT/Alb比值对慢性HBV感染者肝纤维化的无创诊断价值
DOI: 10.3969/j.issn.1001-5256.2021.06.019
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明: 何峰负责课题设计，资料分析，撰写论文；何峰、王翔参与收集数据，修改论文；郜玉峰、张照如负责拟定写作思路，指导撰写文章并最后定稿。
Value of gamma-glutamyl transpeptidase/albumin ratio in the noninvasive diagnosis of liver fibrosis in patients with chronic hepatitis B virus infection
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摘要:
目的 评价GGT/Alb比值对慢性HBV感染者肝纤维化程度的无创诊断价值。 方法 回顾分析2018年1月—2020年3月安徽医科大学附属巢湖医院经肝穿刺活检的慢性HBV感染者资料。根据肝穿刺病理检查结果，将322例患者按照肝纤维化程度分为S0~1(183例)、S2(68例)、S3(35例)、S4(36例)。收集患者的血常规、病毒学、血生化等临床指标。正态分布的计量资料多组间比较采用单因素方差分析，非正态分布的计量资料多组间比较采用Kruskal-Wallis H秩和检验; 计数资料采用χ2检验。采用Spearman等级相关分析评估3种无创模型GGT/Alb比值、APRI评分和FIB-4指数与肝纤维化程度的相关性。绘制GGT/Alb比值的受试者工作特征曲线(ROC)评价其诊断价值。 结果 随着肝纤维化程度的加重，患者的Alb(F=7.351)、HBV DNA(χ2=2.820)和PLT(F=6.182)逐渐降低，而年龄(χ2=3.145)、GGT(χ2=6.149)、GGT/Alb比值(χ2=7.064)、APRI评分(χ2=9.022)和FIB-4指数(χ2=8.254)逐渐升高，差异有统计学意义(P值均＜0.05)。Spearman等级相关性分析得出，GGT/Alb比值与肝纤维化分期呈正相关(r=0.396，P＜0.01)，其相关系数高于APRI评分(r=0.327，P＜0.01)和FIB-4指数(r=0.370，P＜0.01)。ROC曲线结果显示，在显著肝纤维化、严重肝纤维化和肝硬化患者中，GGT/Alb比值的ROC曲线下面积(AUC)(分别为0.680、0.676、0.695)与APRI评分(AUC分别为0.692、0.698、0.728)和FIB-4指数(AUC分别为0.659、0.661、0.684)相当，差异均无统计学意义(P值均＞0.05)。GGT/Alb比值分别以0.435、0.465和0.465为截断值，其用于诊断显著肝纤维化、严重肝纤维化和肝硬化患者的灵敏度分别为69.1%、66.2%和69.0%，特异度分别为65.4%、65.9%和67.0%。 结论 与APRI评分和FIB-4指数一样，GGT/Alb比值是一种简单、实用的肝纤维化无创诊断模型，可以对慢性HBV感染者肝纤维程度的诊断提供参考价值。 Abstract:Objective To investigate the value of gamma-glutamyl transpeptidase (GGT)/albumin (Alb) ratio in the noninvasive diagnosis of liver fibrosis degree in patients with chronic hepatitis B virus (HBV) infection. Methods A retrospective analysis was performed for the clinical data of 322 patients with chronic HBV infection who underwent liver biopsy in Chaohu Hospital of Anhui Medical University from January 2018 to March 2020, and according to liver fibrosis degree based on liver biopsy, the 322 patients were divided into S0-S1 group with 183 patients, S2 group with 68 patients, S3 group with 35 patients, and S4 group with 36 patients. The clinical indices of routine blood test, virology, and blood biochemistry were collected. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups; the chi-square test was used for comparison of categorical data. A Spearman rank correlation analysis was used to investigate the correlation of the three noninvasive models GGT/Alb ratio, aspartate aminotransferase-to-platelet ratio index (APRI) score, and fibrosis-4 (FIB-4) index with liver fibrosis degree. A receiver operating characteristic (ROC) curve was plotted for GGT/Alb ratio to evaluate its diagnostic value. Results With the aggravation of liver fibrosis degree, there were gradual reductions in Alb (F=7.351, P < 0.05), HBV DNA (χ2=2.820, P < 0.05), and platelet count (F=6.182, P < 0.05) and gradual increases in age (χ2=3.145, P < 0.05), GGT (χ2=6.149, P < 0.05), GGT/Alb ratio (χ2=7.064, P < 0.05), APRI score (χ2=9.022, P < 0.05), and FIB-4 index (χ2=8.254, P < 0.05). The Spearman rank correlation analysis showed that GGT/Alb ratio was positively correlated with liver fibrosis stage (r=0.396, P < 0.01), with a significantly higher correlation coefficient than APRI score (r=0.327, P < 0.001) and FIB-4 index (r=0.370, P < 0.001). The ROC curve analysis showed that in the patients with significant liver fibrosis, severe liver fibrosis, and liver cirrhosis, GGT/Alb ratio had similar areas under the ROC curve to APRI score and FIB-4 index (0.680/0.676/0.695 vs 0.692/0.698/0.728 and 0.659/0.661/0.684, all P > 0.05). At the optimal cut-off values of 0.435, 0.465, 0.465, respectively, GGT/Alb ratio had sensitivities of 69.1%, 66.2%, and 69.0%, respectively, and specificities of 65.4%, 65.9%, and 67.0%, respectively, in the diagnosis of significant liver fibrosis, severe liver fibrosis, and liver cirrhosis. Conclusion Like APRI score and FIB-4 index, GGT/Alb ratio is a simple and practical noninvasive model for the diagnosis of liver fibrosis and can provide a reference for the diagnosis of liver fibrosis degree in patients with chronic HBV infection. -
Key words:
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- gamma-Glutamyltransferase /
- Albumin
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表 1 不同肝纤维化分期临床指标的比较
临床指标 S0~1(n=183) S2(n=68) S3(n=35) S4(n=36) 统计值 P值 男/女(例) 123/60 47/21 24/11 26/10 χ2=0.378 0.954 HBeAg(阳性/阴性, 例) 121/62 48/20 23/12 25/11 χ2=0.565 0.904 年龄(岁) 35(27~45) 38(30~47) 40(36~48) 48(41~54) χ2=3.145 0.025 PLT(109/L) 176.89±48.96 165.86±52.54 157.05±48.11 140.27±53.17 F=6.182 ＜0.001 ALT(U/L) 28(23~35) 42(25~60) 40(25~52) 40(25~56) χ2=5.202 0.002 AST(U/L) 28(23~35) 35(28~43) 36(26~40) 35(27~40) χ2=6.457 ＜0.001 GGT(U/L) 16(11~30) 27(17~40) 28(15~36) 29(16~40) χ2=6.149 ＜0.001 Alb(g/L) 46.65±2.82 45.18±2.96 40.09±2.87 35.00±3.16 F=7.351 ＜0.001 HBV DNA(lg IU/ml) 5.03(3.74~5.77) 4.60(3.74~6.09) 4.34(3.53~5.71) 3.78(3.13~5.11) χ2=2.820 0.039 GGT/Alb 0.34(0.24~0.62) 0.49(0.28~0.73) 0.60(0.33~0.79) 0.71(0.46~0.97) χ2=7.064 ＜0.001 APRI 0.41(0.31~0.55) 0.56(0.42~0.84) 0.61(0.44~0.89) 1.18(0.82~1.67) χ2=9.022 ＜0.001 FIB-4 1.24(0.91~1.79) 1.55(0.94~2.61) 1.72(0.96~2.59) 1.95(1.11~2.64) χ2=8.254 ＜0.001 
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表 2 GGT/Alb比值、APRI评分和FIB-4指数对慢性HBV感染者肝纤维化程度的预测价值
指标 显著肝纤维化(n=139) 严重肝纤维化(n=71) 肝硬化(n=36) GGT/Alb APRI FIB-4 GGT/Alb APRI FIB-4 GGT/Alb APRI FIB-4 截断值 0.435 0.425 1.560 0.465 0.425 1.560 0.465 0.425 1.67 AUC 0.680 0.692 0.659 0.676 0.698 0.661 0.695 0.728 0.684 95% CI 0.621~0.738 0.634~0.750 0.598~0.719 0.605~0.747 0.626~0.770 0.583~0.739 0.607~0.782 0.639~0.817 0.581~0.787 敏感度(%) 69.1 77.7 66.2 66.2 80.3 69.0 69.0 83.3 69.4 特异度(%) 65.4 53.8 65.9 65.9 53.8 65.9 67.0 53.8 70.9 阳性似然比 2.00 1.68 1.94 2.04 1.74 2.03 2.14 1.81 2.38 阴性似然比 0.47 0.41 0.51 0.50 0.37 0.47 0.45 0.31 0.43 约登指数 0.344 0.315 0.321 0.338 0.341 0.349 0.370 0.372 0.403
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