自身免疫性肝炎患者血清生长分化因子15水平变化及其临床意义

摘要/Abstract

摘要： 目的探究生长分化因子15(GDF15)对自身免疫性肝炎(AIH)诊断和疗效的临床意义。方法纳入2020年7月至2022年7月收治的65例AIH患者,45例健康体检者,乙型肝炎和丙型肝炎患者各40例,35例原发性胆管炎(PBC)患者。比较各组研究对象的临床资料、肝硬化和非肝硬化患者血清GDF15水平。多因素回归分析发生肝硬化的影响因素,ROC曲线下面积评估GDF15的诊断价值。结果 AIH患者ALT、AST、Fib4 指数、IgG以及TBil分别为(368.9±59.8)U/L、(294.6±52.7)U/L、(5.8±2.5)、(2668.3±901.5)mg/dL、(49.6±11.5)μmol/L,健康对照组分别为(24.5±4.8)U/L、(8.4±2.1)U/L、(1.1±0.3)、(476.2±172.8)mg/dL、(3.4±1.3)μmol/L,乙型肝炎组分别为(61.7±25.8)U/L、(50.9±18.5)U/L、(3.2±1.5)、(953.6±253.4)mg/dL、(18.8±5.2)μmol/L,丙型肝炎组分别为(48.4±12.5)U/L、(48.6±21.4)U/L、(4.1±1.6)、(1868.6±539.8)mg/dL、(19.2±5.3)μmol/L,PBC组分别为(59.6±11.2)U/L、(42.3±20.1)U/L、(1.5±0.8)、(641.5±125.8)mg/dL及(12.3±3.7)μmol/L,差异均有统计学意义(P<0.05)。而AIH患者GDF15为(2000.9±699.2)pg/dL,高于对照组(476.2±172.8)pg/dL、乙型肝炎组(953.6±253.4)pg/dL和PBC组(641.5±125.8)pg/dL(P<0.05)。肝硬化AIH患者血清ALT、AST、Fib4指数以及GDF15水平分别为(461.7±55.8)U/L、(298.4±41.1)U/L、(6.1±2.3)及(2045.1±350.8)pg/dL,高于非肝硬化AIH患者的(224.5±24.8)U/L、(80.9±18.5)U/L、(3.8±1.5)及(1305.2±200.2)pg/dL(P<0.05)。GDF15是AIH患者肝硬化发生的独立危险因素(P<0.05)。以GDF15=1639.0 pg/dL为临界点,GDF15诊断AIH肝硬化的AUC、敏感度及特异度分别为0.924、93.3%(14/15)和82.5%(33/40)。结论 AIH患者的GDF15水平较高,对评估AIH患者是否发生肝硬化具有一定应用价值。

关键词: 生长分化因子15, 自身免疫性肝炎, 诊断效能, 疾病进展

Abstract: Objective To evaluate the utility of growth differentiation factor 15 (GDF15) as a biomarker in the diagnosis and therapeutic management of autoimmune hepatitis (AIH).Methods Data were retrospectively analyzed from 65 patients with AIH, 45 healthy individuals, 40 patients with hepatitis B (HB) and hepatitis C (HC), and 35 patients with primary biliary cholangitis (PBC). These individuals, admitted to our hospital from July 2020 to July 2022, were categorized as the AIH group, healthy control group, HB group, HC group and PBC group, respectively. Clinical baseline data among these diverse liver disease patient groups and the control group were compared. In particular, the serum levels of GDF15 were analyzed for both cirrhosis and non-cirrhosis patients. Additionally, in the AIH group, serum GDF15 levels in patients with cirrhosis were compared to those without cirrhosis, and multivariate regression analysis was performed to assess the correlation of GDF15 levels with the occurrence of cirrhosis and the area under the (ROC) curve for GDF15 was calculated.Results In patients with AIH, levels of ALT, AST, Fib4 index, IgG and TBil were found to be significantly elevated. These levels were meaused at(368.9±59.8)U/L, (294.6±52.7)U/L, (5.8±2.5), (2668.3±901.5)mg/dL and(49.6±11.5) μmol/L, respectively, which were higher compared to the healthy control group[(24.5±4.8 )U/L,(8.4±2.1)U/L,(1.1±0.3),(476.2±172.8)mg/dL and (3.4±1.3)μmol/L], HB group [(61.7±25.8)U/L,(50.9±18.5)U/L,(3.2±1.5),(953.6±253.4)mg/dL and (18.8±5.2)μmol/L], HC group [(48.4±12.5)U/L,(48.6±21.4)U/L,(4.1±1.6),(1868.6±539.8)mg/dL and(19.2±5.3)μmol/L] and PBC group [(59.6±11.2)U/L,(42.3±20.1)U/L,(1.5±0.8),(641.5±125.8)mg/dL and (12.3±3.7)μmol/L] (P<0.05). Additionally, GDF15 levels were(2000.9±699.2)pg/dL, which were higher compared to the control group, HB group and PBC group [(476.2±172.8)pg/dL, (953.6±253.4)pg/dL, and (641.5±125.8)pg/dL, respectively)(P<0.05). In AIH patients with liver cirrhosis, serum levels of ALT, AST, Fib4 index and GDF 15 were significantly higher at (461.7±55.8) U/L, (298.4±41.1) U/L, (6.1±2.3) and (2045.1±350.8)pg/dL, respectively, compared to non-liver cirrhosis AIH patients[(224.5±24.8) U/L, (80.9±18.5) U/L, (3.8±1.5) and (1305.2±200.2)pg/dL, P<0.05]. GDF15 was an independent risk factor for cirrhosis in AIH patients (P<0.05). Using a GDF15 threshold of 1639.0 pg/dL, the area under the curve(AUC), sensitivity and specificity of GDF15 for diagnosing AIH-related cirrhosis were 0.924, 93.3%(14/15) and 82.5%(33/40), respectively.Conclusion The levels of GDF15 in AIH patients are elevated, indicating that GDF15 measurement can aid in the diagnosis of AIH. This finding demonstrates significant potential for evaluating therapeutic efficacy, suggesting that GDF15 testing could have considerable application value and merits further clinical implementation.

Key words: Growth differentiation factor 15, Autoimmune hepatitis, Diagnosis, Therapeutic efficacy

庞雪花, 林懋惺, 刘宏. 自身免疫性肝炎患者血清生长分化因子15水平变化及其临床意义[J]. 肝脏, 2023, 28(12): 1484-1486.

PANG Xue-hua, LIN Mao-xing, LIU Hong. Assessing the diagnostic and therapeutic efficacy of growth differentiation factor 15 (GDF15) in autoimmune hepatitis[J]. Chinese Hepatolgy, 2023, 28(12): 1484-1486.

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