B-cell clonality in the liver of hepatitis C virus-infected patients

AIM:The association of hepatitis C virus(HCV) infection with typeⅡmixed cryoglobulinemia is well established,but the role of HCV in B-cell lymphoma remains controversial.In patients with HCV infection,B-cell clonal expansions have been detected in peripheral blood and bone marrow,and a high prevalence of B-cell non-Hodgkin's lymphomas has been documented.Liver biopsies in chronic HCV infection frequently show portal lymphoid infiltrates with features of B follicles,whose clonality has not yet been investigated.The object of this study was to determine the frequency of liver-infiltrating monoclonal B-cells in 40 patients with HCV infection.METHODS:Eight hundred and forty-eight patients were studied prospectively,including 40 HCV-positive patients and 808 patients with chronic hepatitis B virus(HBV)infection.Immunohistochemical study for B-and T-cell markers was performed on the paraffin-embedded liver tissue sections.The clonality of lymphoid B-cells was tested using a polymerase chain reaction(PCR)approach designed to identify immunoglobulin heavy chain gene(IgH) rearrangements.RESULTS:Liver-infiltrating monoclonal B-cells were detected in the liver for 4(10%)of 40 HCV-positive patients but were present in only 3(0.37%)of 808 liver biopsy specimens with chronic HBV infection.Chi-square testing showed that the monoclonal B-cells infiltration in the liver was more frequent in the HCV-infected patients(P=0.000).A clonal IgH rearrangement was detected in 5(71.4%)of 7 liver biopsy specimens with monoclonal B-cells infiltration.In 2 of 5 patients with both a clonal B-cell expansion and monoclonal B-cells infiltration in the liver,a definite B-cell malignancy was finally diagnosed.CONCLUSION:Liver-infiltrating monoclonal B-cells are detected in the liver of patients with chronic HCV and HBV infection.A high percentage of patients with monoclonal B-cells infiltration and B-cell clonality in the liver were finally diagnosed as having a definite B-cell malignancy.

Use of ^(18)F-FDG PET/CT to locate primary malignancies in patients with hepatic cirrhosis and malignant ascites

Objective：Ascites in patients with hepatic cirrhosis is caused by cirrhosis in most cases.For most malignant ascites,the primary malignancy could be readily identified using conventional imaging methods,e.g.,computer tomography （CT） and magnetic resonance imaging （MRI）.However,in a small fraction of the patients,the primary malignancy remains occult even with these examinations.In this retrospective study,we assessed the usefulness of 18F-FDG PET/CT in patients with hepatic cirrhosis and malignant ascites of otherwise unknown origin.Methods：Twenty-eight patients with malignant ascites of unknown primary sites after CT,MRI and ultrasound during the period of five years between January 2008 and December 2012 had received 18F-FDG PET/CT.Medical records of these patients were reviewed and analyzed.Results：Elevated 18F-FDG absorption was found in 23 of 28 cases in the following sites：gastrointestinal tract （n=10,43.5％）,prostate （n=5,21.7％）,peritoneum （n=4,13.3％）,and ovary （n=4,13.3％）.Cancer was confirmed by pathology in 20 cases after open or laparoscopic surgeries.Five patients were found to have benign ascites,among which,3 were found to be false positive due to tuberculosis.SUV values were significantly higher for tumors than for benign lesions （mean values,6.95 vs.2.94; P=0.005）.Conclusions：The 18F-FDG PET/CT can be as a powerful imaging tool in identifying tissue origin in liver cirrhosis patients suspected of cancers or with cancers of unknown primary sites.

Silencing of UBP43 by shRNA Enhances the Antiviral Activity of Interferon against Hepatitis B Virus

Previous studies have shown that expression of the interferon-sensitive gene （ISG）15 protease UBP43 is increased in the liver biopsy specimens of patients who do not respond to interferon （IFN）-α therapy. We hypothesized that UBP43 might hinder the ability of IFN to inhibit HBV replication. In this study, we investigated whether vector-based siRNA promoted by HI （psiUBP43） could enhance IFN inhibiting HBV replication in cell culture. UBP43 was specifically silenced using shRNA. In HepG2.2.15 cells, the HBeAg and HBV DNA levels were significantly reduced by IFN after transfection of shRNA, imphicated that vector-based siRNA promoted by H1 （psiUBP43） could enhance IFN inhibiting HBV replication in cell culture. These data suggest that UBP43 modulates the anti-HBV type I IFN response, and is a possible therapeutic target for the treatment of HBV infection.