Relationship between multicentric occurrence of hepatocellular carcinoma and histology of noncancerous hepatic tissue in patients with chronic hepatitis C

The relationship between multicentric occurrence of hepatocellular carcinom a (HCC) and the histology of noncancerous hepatic tissue was investigated i n 252 patients infected with hepatitis C virus (HVC) and surgically treated for HCC. One type of multicentric HCC had at least one tumor consisting of well-differentiated HCC, together with moderately or poorly differentiated HCC located in a separate region. The other type had an area of well-diffe rentiated component around HCC with less differentiation in all occurrences . Noncancerous hepatic tissues were assessed using a histologic activity in dex score. Serum alanine aminotransferase (ALT) activity, the concentration of type 4 collagen, the grading score (severity of active hepatitis), and the staging score (degree of fibrosis) were significantly higher in patient s with multicentric HCCs than in those without them. Platelet count was sig nificantly lower in patients with multicentric HCCs. The prevalence of mult icentric HCCs increased as the grading score and staging score increased. O n univariate analysis, a low platelet count and high grading and staging sc ores were risk factors for multicentric HCCs, A high ALT activity and a hig h concentration of type 4 collagen tended to be risk factors. On multivaria te analysis, high grading score and high staging score were independent ris k factors. These findings indicate that active hepatitis and extensive fibr osis are responsible for the development of multicentric HCCs. Measurement of platelet count, ALT activity, and the concentration of type 4 collagen, and histologic assessment of noncancerous hepatic tissue provide informatio n useful for estimation of the potential for multicentric carcinogenesis.