Castaldo G, Oriani G, Lofrano M M, Cimino L, Topa M, Budillon G, Salvatore F, Sacchetti L
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Clin Chem. 1996 Aug;42(8 Pt 1):1263-9.
We applied a multivariate analysis to a large series of serum biochemical tests in an attempt to identify a function that could efficiently discriminate cirrhosis from hepatocellular carcinoma (HC). We analyzed two successive temporal cohorts (1987-90; 1991-94) of HC and cirrhotic patients, all histologically classified (first cohort: 69 cirrhosis and 39 HC; second cohort: 66 cirrhosis and 38 HC). Using data from the first temporal cohort of patients, we obtained a discriminant function based on seven serum analytes: alpha-fetoprotein, the hepatic isoenzyme of alkaline phosphatase, lactate dehydrogenase isoenzyme 5, total gamma-glutamyltransferase (GGT), GGT isoforms complexed with low-density lipoprotein, aspartate aminotransferase, and copper. The same panel of analytes emerged when the second cohort was tested and also when both cohorts were tested together. In the two successive cohorts (total, 212 patients) with a prevalence of cirrhosis vs HC of approximately 2:1, the discriminant function correctly classified 93% of cases, the highest percentage of correct classification of the two diseases obtained so far by laboratory approaches. Validation with the jackknife reallocation statistical algorithm confirmed these results. In addition, of six patients with liver cirrhosis for whom we had the opportunity of following up and observing the evolution to HC, five were classified as HC at diagnosis by the multivariate discriminant analysis; i.e., discriminant analysis provided a diagnostic lead time of 6-12 months over histology. This discriminant function, based on easy-to-perform serum biochemical tests, may help solve a fundamental problem of differential diagnosis in the evolution of chronic liver diseases from cirrhosis to HC.
我们对一系列大量的血清生化检测进行了多变量分析，试图找出一种能够有效区分肝硬化与肝细胞癌（HC）的功能。我们分析了两个连续时间段的HC和肝硬化患者队列（1987 - 90年；1991 - 94年），所有患者均经组织学分类（第一个队列：69例肝硬化患者和39例HC患者；第二个队列：66例肝硬化患者和38例HC患者）。利用第一个时间段患者队列的数据，我们基于七种血清分析物获得了一个判别函数：甲胎蛋白、碱性磷酸酶的肝同工酶、乳酸脱氢酶同工酶5、总γ-谷氨酰转移酶（GGT）、与低密度脂蛋白结合的GGT同工酶复合物、天冬氨酸氨基转移酶和铜。在对第二个队列进行检测时以及将两个队列一起检测时，出现了相同的分析物组合。在肝硬化与HC患病率约为2:1的两个连续队列（共212例患者）中，判别函数正确分类了93%的病例，这是目前通过实验室方法对这两种疾病进行正确分类的最高百分比。采用留一法重新分配统计算法进行验证证实了这些结果。此外，在我们有机会随访并观察到演变为HC的6例肝硬化患者中，多变量判别分析在诊断时将其中5例分类为HC；也就是说，判别分析比组织学诊断提前了6 - 12个月。这种基于易于进行的血清生化检测的判别函数，可能有助于解决慢性肝病从肝硬化演变为HC过程中鉴别诊断的一个基本问题。
