Objectives: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).
Methods: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.
Results: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).
Conclusions: The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
目的: 长期的乙型肝炎病毒(hepatitis B virus，HBV)感染可引起肝脏反复出现炎症坏死，进而发展为肝纤维化、肝硬化甚至肝癌。肝脏病理改变程度是指导慢性乙型肝炎(chronic hepatitis B，CHB)患者抗病毒治疗的重要依据之一。由于肝穿刺活检临床使用的局限性，有必要寻找到更好的无创性指标以评估CHB患者的肝脏病变程度，指导抗病毒治疗。本研究旨在分析CHB患者不同程度肝脏病变的临床特征，并探索谷丙转氨酶(alanine aminotransferase，ALT)正常的CHB患者肝脏炎症及纤维化程度的影响因素。方法: 回顾性纳入完善肝脏病理活体组织检查(以下简称“活检”)的CHB患者310例。收集患者临床资料，以肝脏病理活检结果为金标准，分析总体样本相关临床指标与肝脏病理改变程度的关系。筛选ALT正常的CHB患者，探索影响其肝脏炎症及纤维化程度的独立危险因素。结果: 310例CHB患者中，显著性肝脏炎症[肝脏炎症程度分级(liver inflammation grade，G)≥2]和显著性肝纤维化[肝纤维化程度分期(liver fibrosis stage，S)≥2]的患者分别为249例(80.3%)和119例(38.4%)。总体样本单因素分析结果显示：ALT、谷氨酰转肽酶、碱性磷酸酶水平以及HBV DNA定量与显著性肝脏病理改变(G/S≥2)相关(均P<0.05)。ALT正常的132例CHB患者中，肝脏病理G/S≥2、G≥2、S≥2的患者分别为80.3%(106/132)、68.2%(90/132)、43.2%(57/132)。显著性肝脏炎症的独立危险因素为HBV DNA定量>2 000 U/mL(OR=3.592，95% CI 1.534~8.409)；显著性肝纤维化的独立危险因素为碱性磷酸酶升高(OR=1.022，95% CI 1.002~1.043)、血小板计数降低(OR=0.990，95% CI 0.982~0.998)及乙型肝炎e抗原(hepatitis B e antigen，HBeAg)阳性(OR=14.845，95% CI 4.898~44.995)。根据多因素分析建立ALT正常的CHB患者显著性肝纤维化诊断模型，并绘制受试者操作特征曲线，曲线下面积为0.844(95% CI 0.779~0.910)。结论: 肝脏的病理改变程度需综合不同临床指标进行评估。ALT正常的CHB患者中仍有相当一部分存在肝脏显著病理改变，需及时识别并进行抗病毒治疗。在这部分患者中，HBV DNA定量>2 000 U/mL提示存在显著性肝脏炎症；而基于碱性磷酸酶、血小板计数及HBeAg水平建立的显著性肝纤维化诊断模型有助于评估肝脏纤维化程度。.
Keywords: chronic hepatitis B; clinical indicators; fibrosis; inflammation; liver histopathology.