非酒精性脂肪性肝病对儿童和青少年慢性乙型肝炎抗病毒治疗反应的影响

摘要/Abstract

摘要： 目的分析非酒精性脂肪性肝病(NAFLD)对儿童和青少年慢性乙型肝炎(CHB)抗病毒治疗反应的影响。方法回顾2013年3月至2019年4月儿童和青少年CHB患者316例(男247例、女69例),年龄6.6(3.0,15.5)岁。根据患者是否合并NAFLD,其中合并NAFLD 78例(NAFLD组)[男57例,女21例,年龄为6.3(2.5,15.8)岁],未合并NAFLD患者238例(非NAFLD组)[男190例,女48例,年龄为6.7(3.2,15.6)岁]。计量资料以±s表示,采用t检验,计数资料以例数(%)表示,采用卡方检验。结果 NAFLD组、非NAFLD组BMI分别为21.6(19.7,24.4)kg/m²、19.6(17.5,22.0)kg/m²,差异具有统计学意义(P<0.05);两组肝脾CT值比分别为1.1(0.9,1.2)、0.6(0.5,0.8),差异具有统计学意义(P<0.05);非NAFLD组ALT、AST、TC、TG、球蛋白、前白蛋白及纤维蛋白原分别为87(51,142)U/L、68(45,110)U/L、3.6(3.2,4.1)mmol/L、0.9(0.7,1.1)mmol/L、26.7(24.1,29.2)g/L、152(138,185)mg/L及2.7(2.4,3.3)g/L,与合并NAFLD患者[98(58,172)U/L、82(48,140)U/L、4.8(3.4,5.8)mmol/L、1.4(0.9,1.9)mmol/L、23.8(22.0,26.4)g/L、140(120,167)mg/L及2.4(1.9,2.8)g/L]比较,差异具有统计学意义(P<0.05)。NAFLD组、非NAFLD组抗病毒治疗24周HBV DNA转阴率为217例(91.1%)、53例(69.7%),差异具有统计学意义(P<0.05),而两种抗病毒治疗后12周HBV DNA转阴率差异无统计学意义(P<0.05);两组抗病毒治疗12周ALT复常率为138例(58.0%)、30例(38.5%),差异具有统计学意义(P<0.05),AST复常率为154例(64.7%)、32例(41.0%),差异具有统计学意义(P<0.05)。两组抗病毒治疗24周ALT复常率为166例(69.7%)、41例(53.9%),差异具有统计学意义(P<0.05),AST复常率为180例(75.6%)、44例(57.9%),差异具有统计学意义(P<0.05)。CHB、合并NAFLD抗病毒治疗24周HBV DNA应答为238例(100%)、61例(80.2%),差异具有统计学意义(P<0.05)。比较合并NAFLD中应答、未应答患者临床资料,应答组肝脾CT值比、TC、ALT、AST及HBV DNA为0.7(0.5,0.8)、3.0(2.3,3.7)mmol/L、42(28,74)U/L、44(28,78)U/L及6.4(6.1,8.3)log₁₀ 拷贝/mL,与未应答组[0.5(0.4,0.6)、3.8(3.2,5.0)mmol/L、64(37,92)U/L、70(28,98)U/L及7.3(6.3,8.5)log₁₀拷贝/mL]比,差异具有统计学意义(P<0.05)。结论抗病毒治疗期间,儿童和青少年CHB患者合并存在NAFLD时可影响血生化指标,对早期抗病毒治疗应答产生影响。

关键词: 非酒精性脂肪性肝病, 慢性乙型肝炎, 抗病毒治疗

Abstract: Objective To analyze the influence of nonalcoholic fatty liver disease (NAFLD) on antiviral treatment response of children and adolescents with chronic hepatitis B (CHB). Methods From March 2013 to April 2019, there were 316 children and adolescents with CHB were enro[jg1]lled in this study. Within them, 76 patients including 63 males and 13 females had NAFLD, with an average age of 6.6 (3.0, 15.5) years. Another 238 patients including 182 male and 56 female only had CHB, with an average age of 6.0 (3.0, 13.5) years old. The CHB patients were divided into CHB with NAFLD group and CHB alone group according to whether they were complicated with NAFLD or not. Measurement data were expressed as mean±standard deviation (±s) and analyzed with T test. Counting data were expressed as percentage (%) and analyzed with Chi square test. Results The BMI of CHB with NAFLD group [21.6 (19.7, 24.4) kg/m²] was significantly higher than that of CHB alone group [19.6(17.5, 22.0) kg/m²] (P<0.05). The ratio of liver and spleen CT values in CHB with NAFLD group were 1.1(0.9, 1.2), which were significantly higher than those of 0.6(0.5, 0.8) in CHB alone group (t=-11.635, P<0.05). The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and total glycerol (TG), pre-albumin, and fibrinogen in CHB alone group were 87 (51, 142) U/L, 68 (45, 110) U/L, 3.6 (3.2, 4.1) mmol/L and 0.9(0.7, 1.1)mmol/L, 26.7(24.1,29.2)g/L、152(138,185)mg/L及2.7(2.4,3.3)g/L, respectively, which were significantly lower than those of 98(58, 172) U/L, 82 (48, 140) U/L, 4.8(3.4, 5.8)mmol/L,1.4(0.9, 1.9)mmol/L,23.8(22.0,26.4)g/L,140(120,167)mg/L,and 2.4(1.9,2.8)g/L in CHB with NAFLD group [t=4.370, 6.517, 8.610, 12.005, P<0.05)]. After 24 weeks antiviral treatment, the HBV-DNA seroconversion rates in the CHB with NAFLD group and CHB alone group were 217 cases (91.1%) and 53 cases (69.7%), respectively, with significant difference (P<0.05).There was no significant difference between the HBV-DNA seroconversion rates of these two groups after 12 weeks antiviral treatment. In addition, the ALT and AST normalization rates of CHB alone group at 12 and 24 weeks were 138 cases (58.0%) and 154 cases(64.7%), and 166 cases (69.7%) and 180 cases (75.6%), respectively, which were significantly higher than those of 30 cases (38.55) and 32 cases(41.0%), and 41 cases (53.9%) and 44 cases (57.9%) of the CHB with NAFLD group, respectively, with statistical significant difference (P<0.05). The HBV DNA responsive rate of antiviral treatment for 24 weeks in CHB alone group (238 cases, 100%)were significantly higher than that of CHB with NAFLD group(61 cases,80.2%)(P<0.05). When comparing the anti-viral treatment responsive and non-responsive CHB patients with NAFLD, the ratio of liver and spleen CT values, TC, ALT, AST and HBV DNA of the responsive patients were 0.7(0.5, 0.8), 3.0(2.3, 3.7)mmol/L, 42(28, 74)U/L and 44(28, 78) U/L, respectively,which were significantly different with those of [0.5(0.4, 0.6), 3.8(3.2, 5.0)mmol/L, 64(37, 92)U/L, 70(28, 98)U/L and 7.3(6.3, 8.5)log10 copies/ml in the non-response patients (t=-4.440, 6.746, 13.082, 15.146, 9.320, P<0.05)]. Conclusion The presence of NAFLD in children and adolescent CHB patients may affect their biochemical responsiveness and viral clearance to anti-viral treatment.

Key words: Nonalcoholic fatty liver disease, Chronic hepatitis B, Antiviral therapy;children and adolescents

王晓伟, 孙静, 王栋. 非酒精性脂肪性肝病对儿童和青少年慢性乙型肝炎抗病毒治疗反应的影响[J]. 肝脏, 2022, 27(5): 557-560.

WANG Xiao-wei, SUN Jing, WANG Dong. Effect of nonalcoholic fatty liver disease on antiviral treatment response of children and adolescents with chronic hepatitis B[J]. Chinese Hepatolgy, 2022, 27(5): 557-560.

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