Serum laminin and type III procollagen in chronic hepatitis C. Diagnostic value in the assessment of disease activity and fibrosis.

Laminin P1 (pepsin-resistant fragment of laminin) and aminoterminal peptide of type III procollagen are measurable in serum and are now considered useful serum markers of fibrogenesis and inflammation in chronic liver diseases. However, very few studies thus far have focused on assessing the diagnostic value of these markers in detecting fibrosis and necro-inflammatory activity in chronically diseased liver. The aim of the present study was therefore to investigate the correlations of laminin and type III procollagen with liver histology and to compare their diagnostic value in detecting the degree of liver fibrosis and necro-inflammatory activity in a homogeneous group of 99 patients suffering from chronic hepatitis C, and lacking other factors which can directly affect the serum levels of the two markers. Both these serum markers were measured by radioimmunoassay, employing commercially available kits. The three main aspects of liver pathology, i.e. portal-periportal activity, lobular activity and fibrosis, were histologically evaluated and semiquantitatively expressed by numerical scores. The results of this study show that laminin and type III procollagen were both positively correlated with the histological scores for portal-periportal activity and with those for fibrosis, whereas no significant correlation was observed between each of the two serum markers and the histological scores for lobular activity. The sensitivity and specificity of laminin and type III procollagen in detecting histological aspects of fibrosis and disease activity in liver, computed at various cut-off levels, showed overlapping trends for the two markers; however, the diagnostic value was in general rather low, whatever the cut-off considered. We therefore conclude that the 'static' measurement of both serum laminin and type III procollagen is of limited value for individual diagnosis of liver damage.

Cryoglobulinemia in hepatitis C virus chronic active hepatitis: effects of interferon-alpha therapy.

We investigated the prevalence of mixed cryoglobulinemia (MC) in 100 cases of chronic hepatitis C virus (HCV) infection and the effect of a 6-month treatment with interferon-alpha (IFN-alpha). Cryoglobulins were detected on admission in 36 of 100 patients and appeared during observation in a further 18 cases. Cryocrit ranged from 0.5% to 20%. Patients with MC were older and had a higher incidence of cirrhosis than those without MC. Immunologic characterization of the cryoprecipitate showed the presence of type II in 84% of cases and type III in 16%. The patients received IFN-alpha (6 MU three times per week) for 6 months. Fifty-seven were responders (i.e., reached normal aminotransferase levels), 26 of these relapsed within 2 months after IFN withdrawal, and 30 did not relapse. After IFN-alpha treatment, cryoglobulinemia disappeared in 11 of the 21 evaluable responders, but in none of the 15 nonresponder patients (p < 0.003). The clearance of MC was associated in all cases with clearance of HCV RNA. The delayed appearance of cryoglobulinemia in responders seems to be associated with a higher probability of relapse.