The results of this study indicate that DCP determination by sensitive enzyme immunoassay is useful in the early diagnosis of HCC because a high specificity is maintained.

There has been increased interest in the role of B cells in the pathogenesis of primary biliary cirrhosis. Although the vast majority of patients with primary biliary cirrhosis have antimitochondrial antibodies, there is no correlation of antimitochondrial antibody titer and/or presence with disease severity. Further, in murine models of primary biliary cirrhosis, it has been suggested that depletion of B cells may exacerbate biliary pathology. To address this issue, we have focused on detailed phenotypic characterization of mononuclear cell infiltrates surrounding the intrahepatic bile ducts of patients with PBC, PSC, AIH, CH-C and GVHD, including CD3, CD4, CD8, CD20, CD38 and immunoglobulin classes, as well as double immunohistochemical staining for CD38 and IgM. Interestingly, CD20 B lymphocytes, which are a precursor of plasma cells, were found in scattered locations or occasionally forming follicle-like aggregations but were not noted at the proximal location of chronic nonsuppurative destructive cholangitis. In contrast, there was a unique and distinct coronal arrangement of CD38 cells around the intrahepatic ducts in primary biliary cirrhosis but not controls; the majority of such cells were considered plasma cells based on their expression of intracellular immunoglobulins, including IgM and IgG, but not IgA. Patients with primary biliary cirrhosis who manifest this unique coronal arrangement were those with significantly higher titers of antimitochondrial antibodies. These data collectively suggest a role of plasma cells in the specific destruction of intrahepatic bile ducts in primary biliary cirrhosis and highlight the increasing interest in plasma cells and autoimmunity.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world, and hepatitis B and C viruses are the main causative agents for high incidence of HCC. 1 Although the mechanisms underlying HCC development have been widely investigated from both points of direct and indirect effects of the viruses, 2 they are still open to debate. Whatever the mechanisms involved, these viral infections are correlated with a slow, long-lasting disease that is a definite risk for neoplastic degeneration.Telomeres are composed of tandem arrays of a short DNA sequence, d(TTAGGG)n in vertebrates, and associated proteins. They are essential genetic elements and stabilize the natural ends of linear eukaryotic chromosomes. 3 The endreplication problem, the inability of DNA polymerases to completely replicate the end of a DNA duplex, 4 results in telomere shortening in proportion to cell replication. 5 Because severity of persistent hepatocellular degeneration might indicate a risk for HCC development, an extent of telomere erosion has a possibility to be a predictor for HCC development in the liver under chronic inflammation.The standard and currently most reliable method for evaluating telomere length uses Southern analysis of terminal restriction fragment (TRF) lengths. 6 TRFs, however, contain DNA other than uniform telomeric repeats, 7 and the analysis requires several micrograms of high-molecular-weight genomic DNAs. In addition, telomere length varies among individuals prior to replicative histories. 8 Although this variation should be normalized before comparison of telomere length among patients, all previous reports describing telomere alteration in chronic liver diseases were unfortunately evaluated without any standardization. 9-12 These technical limitations inherent in the complexity of TRF make it difficult to analyze telomere dynamics using clinical materials, especially in the case that only a small specimen is available.In this study, we first evaluated reliability and reproducibility of a slot-blot analysis to detect alteration of telomeric repeats content. Next, we determined the content in various liver tissues. For comparison of the content in the liver with respect to chronic inflammation, we standardized the content

N-Acetylglucosaminyltransferase III (GnT III) catalyses the addition of N-acetylglucosamine through a beta 1-4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin A (Con A)-reactive glycan into a non-reactive state. In this study, we measured GnT III activity to evaluate its diagnostic efficacy and its therapeutic effect on hepatocellular carcinoma (HCC). Concanavalin A-non-reactive fraction of serum transferrin (Tf) was also determined since the sugar chains of Tf are one of the possible candidates for the product of GnT III. Serum samples (159) were used from patients with HCC (89), liver cirrhosis (30), chronic hepatitis (19), alpha-fetoprotein (AFP) producing gastric carcinoma metastatic to the liver (five) and healthy controls (16). N-Acetylglucosaminyltransferase III activity was determined by high performance liquid chromatography. The reactivity of serum Tf to Con A was also analysed in 21 paired HCC samples before and after treatment by crossed immuno-affinoelectrophoresis. N-Acetylglucosaminyltransferase III activity from the HCC group (153 +/- 72pmol/mL/h) was significantly higher than that from liver cirrhosis (99 +/- 67 pmol/mL per h), chronic hepatitis (84 +/- 39 pmol/mL per h) and the normal controls (62 +/- 16 pmol/mL per h). N-Acetylglucosaminyltransferase III activity of 21 patients with HCC was significantly reduced after treatment such as transcatheter arterial chemoembolization and/or percutaneous ethanol infection therapy, (123 +/- 77 to 100 +/- 60 pmol/mL per h). Commensurate decreases of AFP and des-gamma-carboxy prothrombin with GnT III activity were also observed after treatment. The Con A-non-reactive fraction (n = 21; 6.4 +/- 2.3%) in patients with HCC after treatment was significantly lower than before (8.2 +/- 2.4%). The present study suggests that GnT III activity is a possible aid in the diagnosis and evaluation of HCC, especially when other tumour markers are negative.

The present study demonstrated that there was a close association between tumor invasiveness and GnT-V activity in sera, and that the measurement of GnT-V may improve prognostic estimates and therapeutic outcomes for patients with HCC.