Plebani M, Burlina A
Department of Clinical Biochemistry, University of Padova, Italy.
Clin Biochem. 1991 Jun;24(3):219-39. doi: 10.1016/0009-9120(91)80013-s.
Most liver diseases lead to a pathobiochemical reaction termed liver fibrosis. This is a dynamic process implying different rates of progression or regression. Thus, histological examination of a liver biopsy is essential for a diagnosis but biochemical tests are necessary for assessing the activity of the process and monitoring its evolution. We review the most important constituents of liver connective tissue and the biochemical tests developed for evaluating liver fibrosis. The aminopeptide of type III procollagen is the most widely used parameter: two different radioimmunoassays have been developed with different affinities for the two circulating forms of the molecule. The determination of serum P3P reveals an elevation of blood levels both in acute and chronic liver diseases. In the first, serum P3P is an index of hepatic necrosis and inflammation which correlates with other biochemical parameters. In the second it is an index of active fibrogenesis. Moreover, in primary biliary cirrhosis this parameter is an independent prognostic variable and an important predictor of survival. Other immunoassays exist for different collagen cleavage products, but their clinical value is not established. Laminin and fibronectin are the principal structural glycoproteins in liver. Fibronectin determination does not seem to be of clinical value in liver disease. In contrast, serum laminin correlates with the severity of portal venous pressure in advanced liver disease. Its concentration parallels the severity of varices and may indicate the risk of bleeding. Hyaluronate is a high molecular weight polysaccharide, raised serum concentrations reflect both its increased synthesis by activated fibroblasts and its impaired catabolism by the liver. Thus, it may be useful for evaluating and monitoring the progression of chronic liver disease. The measurement of the activity of prolyl 4-hydroxylase as well as that of lysine oxidase and other enzymes has been proposed, but their clinical value is not sufficiently demonstrated. A panel of tests (e.g., laminin, hyaluronate and the aminopeptide of type III procollagen) seems to be recommended for a biochemical assessment of liver fibrosis in clinical practice.
大多数肝脏疾病会引发一种称为肝纤维化的病理生化反应。这是一个动态过程，意味着进展或消退的速率不同。因此，肝活检的组织学检查对于诊断至关重要，但生化检测对于评估该过程的活性及其演变监测是必要的。我们综述了肝脏结缔组织的最重要成分以及为评估肝纤维化而开发的生化检测方法。III型前胶原氨基肽是应用最广泛的参数：针对该分子的两种循环形式开发了两种具有不同亲和力的放射免疫测定法。血清P3P的测定显示，在急性和慢性肝脏疾病中血液水平均会升高。在急性疾病中，血清P3P是肝坏死和炎症的指标，与其他生化参数相关。在慢性疾病中，它是活跃纤维生成的指标。此外，在原发性胆汁性肝硬化中，该参数是一个独立的预后变量和生存的重要预测指标。针对不同的胶原裂解产物还存在其他免疫测定法，但其临床价值尚未确立。层粘连蛋白和纤连蛋白是肝脏中的主要结构糖蛋白。纤连蛋白的测定在肝脏疾病中似乎没有临床价值。相比之下，血清层粘连蛋白与晚期肝脏疾病门静脉压力的严重程度相关。其浓度与静脉曲张的严重程度平行，可能表明出血风险。透明质酸盐是一种高分子量多糖，血清浓度升高既反映了活化成纤维细胞合成增加，也反映了肝脏对其分解代谢受损。因此，它可能有助于评估和监测慢性肝病的进展。有人提出测定脯氨酰4-羟化酶以及赖氨氧化酶和其他酶的活性，但其临床价值尚未得到充分证实。在临床实践中，似乎推荐一组检测（例如层粘连蛋白、透明质酸盐和III型前胶原氨基肽）用于肝纤维化的生化评估。
