直接抗病毒药物对持续病毒学应答慢性丙型肝炎患者肝纤维化的影响

摘要/Abstract

摘要： 目的评价直接抗病毒药物(DAAs)治疗对慢性丙型肝炎(CHC)患者肝纤维化状态的改善作用。方法选取2018年1月—2021年12月期间惠州市中心人民医院首诊并接受入院规范化治疗的CHC患者104例,男性65例,女性39例,年龄(45.6±11.2)岁。CHC诊断符合要求,且获得持续病毒学应答(SVR)。比较DAAs治疗前后CHC患者各项指标变化,依据肝病状态分为慢性肝炎、代偿期肝硬化及失代偿期肝硬化,比较各CHC肝病状态治疗前后各肝纤维化指标变化值差异。Logistic二元回归分析进行单因素、多因素分析。结果 DAAs治疗前CHC患者WBC、PLT、ALT、AST及TBil分别为(5.0±1.2)×10⁹/L、(142.6±36.6)×10⁹/L、(62.0±13.7)U/L、(52.8±11.3)U/L及(21.5±5.2)μmol/L,与治疗后相比[(5.3±1.5)×10⁹/L、(171.4±41.3)×10⁹/L、(18.2±3.8)U/L、(21.6±4.1)U/L及(16.1±4.7)μmol/L],差异均有统计学意义(P<0.05);DAAs治疗前CHC患者APRI、FIB-4及LSM分别为(1.2±0.4)、(3.0±1.0)及(11.6±3.7)kPa,均显著高于治疗后[(0.4±0.1)、(1.7±0.7)及(7.3±2.0)kPa,P<0.05]。依据病史、检验指标及影像学资料,将CHC患者分为慢性肝炎(n=67)、代偿期肝硬化(n=22)及失代偿期肝硬化(n=15)等肝病状态。各CHC肝病状态APRI、FIB-4治疗前后变化值分别为(-0.4±0.1)、(-1.4±0.5)及(-1.9±0.9);(-0.4±0.2) 、(-2.2±0.8)及(-4.0±1.7),差异均具有统计学意义(P<0.05);同时三者LSM治疗前后变化值为(-2.3±1.0)、(-4.6±1.5)及(-9.5±3.8)kPa,差异具有统计学意义(P<0.05)。结合既往文献信息,与治疗前比较,慢性肝病患者治疗后LSM检测值降低>30%定义为LSM改善。以CHC患者DAAs治疗后LSM是否改善作为应变量(赋值0=未改善,1=改善),单因素分析得出治疗前ALT、AST、APRI与LSM改善相关。多因素分析显示,治疗前ALT、AST是DAAs治疗CHC患者LSM改善的独立影响因素。结论应用DAAs治疗CHC能够有效改善患者肝纤维化程度,一旦HCV感染确诊,应尽早开展抗HCV治疗,阻止病情进展。

关键词: 慢性丙型肝炎, 直接抗病毒药物, 持续病毒学应答, 肝纤维化

Abstract: Objective To investigate the effect of direct antiviral agents (DAAs) therapy on the improvement of liver fibrosis status in patients with chronic hepatitis C (CHC).Methods From January 2018 to December 2021, 104 patients (65 males and 39 female) with CHC were selected, including, aged (45.6±11.2) years. CHC diagnosis met the criterion and sustained virological response (SVR) was obtained. The changes of indexes of CHC patients before and after DAAs treatment were compared, and they were divided into chronic hepatitis, compensated cirrhosis and decompensated cirrhosis according to their liver disease status, and the changes of liver fibrosis indexes before and after treatment of three CHC liver diseases were compared. Logistic binary regression analysis was performed for univariate and multivariate analysis.Results The white blood cell (WBC), platelet (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) of CHC patients before DAAs treatment were (5.0±1.2) × 10⁹/L, (142.6±36.6) × 10⁹/L, (62.0±13.7) U/L, (52.8±11.3) U/L and (21.5±5.2) μmol/L, which were significant from those after treatment [(5.3±1.5) × 10⁹/L, (171.4±41.3) ×10⁹/L, (18.2±3.8) U/L, (21.6±4.1) U/L and (16.1±4.7) μmol/L], (P<0.05). The aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM) of CHC patients before DAAs treatment were (1.2±0.4), (3.0±1.0) and (11.6±3.7) kPa, which were significantly higher than those after DAAS treatment [(0.4±0.1), (1.7±0.7) and (7.3 ±2.0) kPa, P < 0.05]. According to the medical history, examination indexes and imaging data, CHC patients were divided into chronic hepatitis (n=67), compensated cirrhosis (n=22) and decompensated cirrhosis (n=15). The changes of APRI and FIB-4 in chronic hepatitis, compensated cirrhosis and decompensated cirrhosis before and after treatment were (-0.4±0.1), (-1.4±0.5) and (-1.9±0.9); (-0.4±0.2), (-2.2±0.8) and (-4.0±1.7), and the differences were statistically significant (P<0.05). In addition, before and after treatment, the changes of LSM in the three groups were (-2.3±1.0) kPa, (-4.6±1.5) kPa and (-9.5±3.8) kPa, and the difference was statistically significant (P<0.05). Combined with information from previous literature, a >30% reduction in LSM test values in patients with chronic liver disease after treatment compared to pre-treatment was defined as LSM improvement. Taking whether LSM of CHC patients improved after DAAs treatment as the dependent variable (assignment 0 = no improvement, 1 = improvement), the indexes before treatment were analyzed by univariate analysis, and the results showed that ALT, AST and APRI before treatment were related to LSM improvement. Further multivariate analysis showed that ALT and AST before treatment were independent influencing factors of LSM improvement.Conclusion DAAs can effectively improve the degree of liver fibrosis in patients with CHC. Once HCV infection is diagnosed, anti-HCV treatment should be started as soon as possible to prevent the progression of the disease.

Key words: Chronic hepatitis C, Direct acting antivirals , Sustained virological response, Hepatic fibrosis

严景全, 刘娟, 卢雪兰, 蓝云翠, , 林占洲. 直接抗病毒药物对持续病毒学应答慢性丙型肝炎患者肝纤维化的影响[J]. 肝脏, 2023, 28(5): 530-533.

YAN Jing-quan, LIU Juan, LU Xue-lan, LAN Yun-cui, LIN Zhan-zhou. Effect of direct antivirals on liver fibrosis in patients with persistently virologically responsive chronic hepatitis C[J]. Chinese Hepatolgy, 2023, 28(5): 530-533.

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