Acarboxy prothrombin (PIVKA II) as a tumour marker for hepatocellular carcinoma and other liver diseases.

The clinical usefulness of plasma abnormal prothrombin, defined as protein induced by vitamin K absence or antagonist II: (PIVKA II) as a tumour marker for hepatocellular carcinoma (HCC) and other liver diseases has been evaluated. PIVKA II concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) with monoclonal antibody that reacts with PIVKA II but does not cross-react with normal prothrombin. Seventy four patients (74%) out of 100 with HCC had abnormal PIVKA II levels above 0.5 AU/ml (median = 3.4 AU/ml). The level was above 1.0 AU/ml in 66 (66%) of the patients. In contrast the level of PIVKA II was low in patients with bilharzial periportal fibrosis (median = 0.09 AU/ml), patients with liver cirrhosis (median = 0.13 AU/ml), patients with hepatitis (median = 0.025 AU/ml), and essentially undetectable in all the 34 controls. The diagnostic ability of serum alphafoetoprotein (AFP) was also evaluated in these patients. AFP alone can diagnose 51% of the HCC cases. Of the remaining patients with low or negative AFP levels (65%) can be diagnosed using PIVKA II. Abnormal prothrombin is a potential marker for the laboratory diagnosis of hepatocellular carcinoma.

Polymorphonuclear leucocyte locomotion and aggregation in patients with alcoholic liver disease.

Defects in stimulated movement of polymorphonuclear (PMN) leucocytes was detected in 57% of patients with alcoholic liver disease. Serum from patients with the cellular defect had no effect on the function of normal PMN leucocytes. Aggregation responses of patients' PMN leucocytes suggest that the cellular defect may be related to specific abnormalities in the response to the C5a chemotactic factor. Defective serum attractant activity was found in 65% of the patients tested and the presence in the patients serum of humoral directed antagonists appeared to be responsible for the defect in majority of cases. Further analysis pointed to the presence of at least two distinct antagonists and the possible involvement of proteases in this serum abnormality. The activity of the serum antagonists or the severity of the cellular defect were unrelated to the presence of bacterial infection or elevations in serum IgA or IgG. The high frequency of cellular defects, possibly as a result of in vivo activation, in conjunction with serum abnormalities could account for the increased susceptibility of patients with alcoholic liver disease to bacterial infection.

Defects in serum attractant activity in different types of chronic liver disease.

Serum attractant activity, measured in 57 patients with chronic liver disease, was significantly reduced in 66% of the 27 patients with alcoholic liver disease and in 29% of the 17 patients with chronic active hepatitis, but was normal in 13 patients with primary biliary cirrhosis despite the presence of established cirrhosis in nearly half of them. In patients with alcoholic liver disease, but not in those with chronic active hepatitis, there was a correlation between the serum defect and severity of liver disease. The defect could not be related to the deficiency of key complement components, raised concentrations of IgA or G or the concurrent presence of bacterial infection. These findings suggest that the aetiology of liver disease may be an important factor in the development of serum attractant abnormalities.

Serum stimulatory activity and polymorphonuclear leucocyte movement in patients with fulminant hepatic failure.

Serum from 27 patients with fulminant hepatic failure and grade IV encephalopathy had reduced ability to stimulate the movement in vitro of normal polymorphonuclear leucocytes. All patients had a deficiency of serum complement factors C3 and C5 and there was a significant positive correlation between C5 and serum stimulatory activity. However, in addition to this complement defect, serum from 22% of patients contained an antagonist to normal serum stimulatory factors. This antagonism was attributed to at least two different substances in the serum on the basis of differences in heat lability, dialysability and action on complement factor C5a. Polymorphonuclear leucocytes from eight of 13 patients had reduced movement toward serum, but serum from only one patient contained an antagonist acting on the cells; this was probably related to an underlying carcinoma of the breast. During the early stages of clinical recovery, serum stimulatory and complement activity returned to normal. These serum and cellular defects have not been reported previously in patients with fulminant hepatic failure and represent major defects in the body's defenses against bacterial infection.

Defects of serum chemoattraction and polymorphonuclear leucocyte movement in patients with primary hepatocellular carcinoma.

Movement of polymorphonuclear leucocytes to the site of tumour cells may be an important stage in host defences against tumours in a variety of organs. In this study, sera from 29 of 30 patients with primary hepatocellular carcinoma had reduced ability to stimulate the movement in vitro of normal polymorphonuclear leucocytes. The serum defect was more severe in 11 patients with underlying cirrhosis but was not related to abnormalities of tests of liver function, levels of serum alphafetoprotein, or deficiency of complement factors C3 and C5. Serial studies showed that the defect was persistent and progressive in patients in whom the tumour did not respond to treatment. In 35% of patients, mainly those with cirrhosis, the sera contained antagonists to normal serum chemotactic factors which were heat stable and dialysable, but could be distinguished by their effect on complement factor C5a. A heat labile dialysable antagonist(s) was found in sera from 28% of the patients (mainly those without cirrhosis) which antagonized the movement of normal polymorphonuclear leucocytes (cell directed antagonism). In addition to these serum defects, polymorphonuclear leucocytes from two of seven patients studied had reduced movement which was not related to the presence in the serum of cell directed antagonists. These serum and cellular defects have not been reported previously in patients with primary hepatocellular carcinoma, and could compromise the body's defences against the tumour.