慢性乙型肝炎患者肝纤维化血清标志物水平与肝纤维化分期的关系

Study on the relationship between serum hepatic fibrosis markers and liver fibrosis stage in patients with chronic hepatitis B

目的探讨慢性乙型肝炎(慢乙肝)患者肝纤维化血清学指标与肝纤维化分期的关系。方法对316例慢乙肝患者(HBeAg阳性者242例、阴性者74例)通过肝穿刺活检组织病理结果确定肝纤维化分期,按照肝纤维化分期将患者分为S1、S2、S3及S4组。采取化学发光免疫分析技术检测患者血清中肝纤4项[透明质酸(HA)、Ⅲ型前胶原氨端肽(PCⅢNP)、Ⅳ型胶原(C-Ⅳ)及层黏连蛋白(LN)]水平;采用全自动生化分析仪检测血清丙氨酸氨基转氨酶(ALT)和天冬氨酸氨基转氨酶(AST)水平。结果 316例慢乙肝患者中,HA、PCⅢNP、C-Ⅳ、LN、ALT、AST水平随肝纤维化分期加重均不断增高,其中各期PCⅢNP、LN水平基本上在正常参考范围内,而HA、C-Ⅳ在S2期即开始出现异常;ALT、AST的含量在S1期即异常升高。242例HBeAg阳性慢乙肝患者血清肝纤四项及转氨酶水平随肝纤维化分期加重均不断增高,与上述总体研究结果基本一致。74例HBeAg阴性慢乙肝患者中,肝纤四项中只有C-Ⅳ在S3期异常升高,而HA和LN均在S4期才出现异常,ALT和AST分别在S1期和S2期即出现异常升高。结论肝纤四项对肝纤维分期的诊断有一定临床意义,其中HA、C-Ⅳ较灵敏,而PCⅢNP最不敏感。另外,肝纤四项联合ALT、AST检测更有利于肝纤维化的早期诊断。肝纤四项诊断HBeAg阳性患者肝纤维化的作用优于HBeAg阴性患者。

Objective It is to explore the relationship between serum hepatic fibrosis markers and liver fibrosis stage in patients with chronic hepatitis B. Methods 316 patients with chronic hepatitis B( 242 ones with positive HBe Ag and 74 ones with negative 74 Hbe Ag) was given liver biopsy to diagnose their liver fibrosis stage,then the patients were divided into S1,S2,S3 and S4 groups according to liver fibrosis stage. The levels of serum hyaluronic acid( HA),type Ⅲ procollagen amino terminal peptide( PCⅢNP),type IV collagen( C-Ⅳ) and laminin( LN) were determined by chemiluminescence immunoassay. The content of serum alanine aminotransferase( ALT) and aspartate aminotransferase( AST) was measured by an automatic biochemical analyzer. Results In 316 patients with chronic hepatitis B,the serum levels of PCⅢNP,LN,HA,C-Ⅳ,ALT and AST were gradually increased when the liver fibrosis stage became severer. The content of PCⅢNP and LN in each period was basically within the normal reference range,while HA and C-Ⅳ began to appear abnormal in S2 phase;the content of ALT and AST increased abnormally in S1 phase. 316 patients with chronic hepatitis B included 242 HBe Ag-positive patients and 74 negative patients. The serum levels of hepatic fibrosis and transaminase in 242 HBe Ag-positive patients increased with the increase of liver fibrosis stage,which was basically consistent with the abovementioned overall results. Among 74 patients with HBe Ag-negative CHB,only C-Ⅳ in the liver fibrosis was abnormally elevated in S3,while both HA and LN were abnormal in S4. However,an abnormal increase of ALT and AST occurred in S1 and S2,respectively. Conclusion Four-item liver fibrosis test may have important significance for the diagnosis of liver fibrosis. Among four-item liver fibrosis test,HA and C-Ⅳ are the most sensitive markers,and PCⅢNP is the least sensitive index. Combined application of four-item liver fibrosis test,ALT and AST is benefit for the early diagnosis of liver fibrosis in patients with chronic hepatitis B. Effect of diagnosis of liver fibrosis for patients with HBe Ag positive using four-item liver fibrosis test is better than that for patients with HBe Ag negative.