代偿性肝硬化无创性诊断指标的筛选及评价

目的：比较肝纤维化血清标志物对慢性乙型肝炎（CHB）代偿性肝硬化的诊断评价，筛选可行的无创性诊断标志物。方法：350例CHB患者经皮肝脏穿刺活检术行病理组织学检查，B型超声波检查肝硬化图像，检测血清透明质酸（HA）、Ⅲ型前胶原肽（PCⅢ）、层黏连蛋白（LN）及Ⅳ型胶原（CⅣ）等肝纤维化标志物。用临床流行病学方法确定诊断截断值，并对各项指标作诊断评价分析，比较不同标志物的诊断评价指标。结果：85例CHB患者经肝脏活检术确认为代偿性肝硬化，81例经B型超声波检查有肝硬化图像，ROC曲线下面积以HA最高；血清HA、PCⅢ、LN及CⅣ对代偿期肝硬化的诊断截断值分别为154．35μg/L、198．44μg/L，137．58μg/L和100．80μg/L，对其应诊断灵敏度分别为82．4％，63．5％，57．3％及70．6％，特异度为79．3％，54．0％，56．8％及68．3％，准确度为80．0％，56．3％，56．9％及68．9％，并联试验诊断虽可提高灵敏度，但相应降低特异度及准确度，与其他无创性诊断方法比较，HA有较高水平的诊断评价指标（u≥1．814，P＜0．05），血清HA诊断代偿性肝硬化的截断值以119．17μg/L较恰当，其相应诊断灵敏度，特异性度，准确度，阳性预告值及阴性预选值分别为87．1％、67．6％、72．3％、46．25％，94．7％。结论：在现有肝脏纤维化血清标志物及超声波检查等无创性诊断指标中，血清HA是代偿性肝硬化最好的诊断标志物。

Screening and evaluation of non-invasive diagnosis markers for compensated liver cirrhosis in patients with chronic hepatitis B

OBJECTIVE: To evaluate the diagnostic value of liver fibrosis markers and ultrasonic examination for determining compensated liver cirrhosis in patients with chronic hepatitis B, and screen applicable non-invasive diagnostic marker for compensated liver cirrhosis. METHODS: Serum hyaluronic acid (HA), Type III procollagen (PCIII), laminin (LN) and Type IV collagen (CIV) were measured from 350 patients with chronic hepatitis B, who were also detected with liver biopsy and ultrasonography. To determine the cut-off value of every serum liver fibrosis marker for diagnosing compensated liver cirrhosis, data was analysed with clinical epidemiology methods. Then evaluated and compared all the markers. RESULTS: 85 out of 350 patients were diagnosed as compensated liver cirrhosis by liver biopsy, and 81 had liver cirrhosis images by ultrasonic examination. HA achieved the biggest area under the ROC curve. The cut-off values with best sensitivity and accuracy of HA, PCIII, LN and CIV were 154.35 microg/L, 198.44 microg/L, 137.58 microg/L and 100.80 microg/L respectively. The related diagnostic sensitivities of HA, PCIII, LN and CIV were 82.4%, 63.5%, 57.3% and 70.6%, specificities were 79.3%, 54.0%, 56.8%, 68.3%, and accuracies were 80.0%, 56.3%, 56.9%, 68.9%, respectively. Parallel tests could increase the diagnostic sensitivity, but decreased specificity and accuracy accordingly. Compared with other non-invasive diagnostic methods, HA was the best marker (mu > or =1.814, P<0.05). The level of HA at 119.17 microg/L was suitable for determining compensated cirrhosis, with a 87.1% sensitivity, 67.6% specificity, 72.3% accuracy, 46.25% positive predictive value and 94.7% negative predictive value. CONCLUSION: Among the non-invasive serum diagnostic markers for liver fibrosis and ultrasonic examination for cirrhosis image, HA is the best marker for diagnosing compensated liver cirrhosis.