Julio Collazos

CA 19-9 in non-neoplastic liver diseases. A clinical and laboratory study.

CA 19-9 is a tumor marker with frequent false-positive results in pancreatic and hepatobiliary diseases. This study was carried out to evaluate the behaviour of CA 19-9 in 159 patients with benign diffuse hepatic disease, 85 cirrhotics and 74 non-cirrhotics, who underwent a thorough clinical and laboratory evaluation. CA 19-9 was correlated with numerous clinical and biochemical features of liver diseases: bilirubin and alkaline phosphatase activity were the most reliable predictors of the CA 19-9 concentrations. There were abnormal concentrations of CA 19-9 in 34.6% of the 159 patients and in 47.1% of the 85 cirrhotics. Because of the large number of abnormal values and the high concentrations attained in some of them, the cut-off used in patients with diffuse hepatic disease needs to be set at more than twice the basal level, thus allows only 10% of false positives. Even higher values are required for cirrhotic or icteric patients. The results indicate that cholestasis plays an important role in causing the raised CA 19-9 in these patients, although there were also abnormal concentrations in normobilirubinemic patients.

Role of the measurement of serum procollagen type III N-terminal peptide in the evaluation of liver diseases

Serum N-terminal procollagen-III peptide (PIIIP) was measured in 151 patients with diverse liver diseases together with other clinical and laboratory data. Patients with cirrhosis had higher serum PIIIP than those without cirrhosis (P < 0.0001). Significant associations were found between PIIIP and many data characteristic of liver diseases, including alcohol markers. Serum PIIIP was also associated with portal hypertension (P = 0.0001), although such association was probably due to the fact that most patients with portal hypertension were cirrhotic patients. The predictive values of PIIIP in portal hypertension were too low to be clinically useful. No one single factor could be identified as responsible for the increase in PIIIP and the data suggest that the mechanism is multifactorial. Measurement of serum PIIIP has a limited clinical value in the evaluation of patients with diverse liver diseases.

Serum laminin levels offer only a little additional information in liver disease

We have measured serum laminin, a marker of portal hypertension, in 151 patients with nonmalignant liver diseases, to evaluate its utility in cirrhosis and portal hypertension. There were abnormal serum levels in 43.1% of the patients as a whole and in 62.7% of the cirrhotics. Laminin showed a correlation with many laboratory tests, especially those that reflect liver insufficiency and alcohol intake. Cirrhotics had higher laminin levels than noncirrhotics (p < 0.0001); an association was also found with portal hypertension (p < 0.0001), but laminin was also increased in patients without portal hypertension. Our results suggest that liver dysfunction can also lead to abnormal laminin concentrations, probably through slower metabolization rate. Laminin serum concentrations reflect the severity of the liver disease, and are also a marker of alcohol consumption. Determination of laminin serum levels could play an adjunctive role with respect to other liver tests in the evaluation of these patients although the measure does not really provide more useful information.

BREAST CANCER-ASSOCIATED ANTIGEN CA 15.3 IN LIVER CIRRHOSIS

The tumor marker CA 15.3 was studied in 85 patients with liver cirrhosis. Nine patients (10.6%) had abnormal levels of CA 15.3 with the highest values in cases of Childs C patients. However, Childs classes were not significantly associated with the level of the antigen. We found significant correlations with some laboratory tests, especially IgA. All patients with an elevated CA 15.3 value also had abnormal levels of IgA, and multivariate analysis showed that IgA was the only independent factor associated with CA 15.3. Although IgA is a marker of alcoholic liver disease, other markers of alcoholism were not associated with CA 15.3. Cytolysis and cholestasis were not significantly associated with the CA 15.3 level, but liver dysfunction seemed to be involved. Liver disease does not substantially limit the usefulness of CA 15.3 in the cancer patient who also has liver cirrhosis, since both the percentage of abnormal values and the elevation of the serum levels are moderate in cirrhotic patients.

A clinical and laboratory evaluation of the behavior of tissue polypeptide antigen in liver cirrhosis.

Serum tissue polypeptide antigen (TPA) was determined in 86 cirrhotic patients who underwent a thorough clinical and laboratory evaluation. Increased serum TPA levels were found in 87.2% of the patients (81% of Childs A, 81.3% of Childs B and 97% of Childs C) with very high levels in some cases. There were significant correlations between TPA and several clinical and biochemical tests, especially AST (r = 0.678, p < 0.000001), and this enzyme was the best predictor of TPA levels. Patients with abnormal AST had also significantly higher serum levels of TPA than those with normal AST in each of the Childs class (p < 0.01 for each). TPA values were found to be more frequently abnormal than AST ones in cirrhotics (p = 0.009) and could be used as indirect markers of activity in these patients. The underlying mechanism involved in the increase in TPA in cirrhosis was probably related to the cytolytic/regenerative activity of the liver. TPA cannot be used as a tumor marker in these patients.

The diagnosis of liver diseases by laboratory tests : an alternative to biopsy

Liver biopsy is still the most reliable procedure for the diagnosis of chronic, diffuse liver disease, so it is performed routinely to elucidate chronic alterations of liver tests. However, expensive and invasive, it is not exempt from risk and has limitations due to sampling error and to the size and quality of the tissue obtained. Moreover, many patients who undergo liver biopsy get no further treatment or do not benefit from treatment when the biopsy results are known. In addition, new biochemical tests have been developed in recent years as noninvasive tools to diagnose liver diseases, particularly fibrosis and cirrhosis. Thus, the role of liver biopsy in the improvement of outcome and quality of life of patients with chronic, diffuse liver diseases should be reconsidered. Many liver biopsies might well be avoided with the rational use of these noninvasive methods without any deleterious effect on patient care. Current tests and future developments in this field should help us to select those patients who would best benefit from a liver biopsy.