Ran Tur-Kaspa — Page 2

PubMed2002

p73 overexpression and nuclear accumulation in hepatitis C virus-associated hepatocellular carcinoma.

p73 is the first identified homolog of p53, but its function has not been established. Our study investigated the expression of p73 in liver tissue of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). RT-PCR was performed on RNA extracted from tumorous and nontumorous liver tissue of HCV-associated HCC, and control tissue and the cDNA were sequenced. Anti-p73 polyclonal antibodies were used for protein analysis and immunohistochemistry, and patients' sera were analyzed for anti-p73 antibodies by radioimmunoassay. Analysis of the p53 gene was performed by SSCP and RFLP-PCR. The p73 mRNA and protein were highly expressed and accumulated in HCC tissues. Immunohistochemical studies revealed significant immunoreactivity in the nuclei of HCC cells. No mutations were detected in the p73 gene or in p53, and no loss of heterozygosity of the p53 gene was found. Anti-p73 antibodies were detected in sera of HCC patients, but were not significantly different from that occurring in non-HCV or non-HCC patients. In conclusion, p73 protein is overexpressed and accumulates in the nuclei of HCV-associated HCCs and may play a role in HCC development.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Recurrent hepatitis C virus disease after liver transplantation and concurrent biliary tract complications: poor outcome.

Recurrent hepatitis C virus (HCV) infection is particularly aggressive in the post-liver transplantation setting, with rapid progression of liver fibrosis. Biliary complications remain a significant cause of morbidity following liver transplantation. Post-cholecystectomy biliary strictures are associated with advanced hepatic fibrosis. The aim of this retrospective study was to determine whether the presence of biliary complications affects survival in liver transplant recipients with recurrent HCV disease. The files of liver transplant recipients (53.7% male; mean age 52.7+/-10.3 yr) were reviewed for incidence, type and treatment of biliary complications, and findings were compared between those who developed recurrent HCV disease (n=47, 83.9%) and those who did not (n=9). Twenty-one biliary complications developed in 12 patients with recurrent HCV (25.5%). Treatment with endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography with balloon dilatation and stent placement or surgical revision was successful in nine (75%). Three biliary complications developed in three patients with no recurrence (p=NS). There was no statistically significant association between recurrent HCV disease and biliary complications. However, among those with recurrent disease, the recurrence was severe in nine of 12 recipients with biliary complications (75%) but in only nine of 35 without biliary complications (26%) (p=0.001). Death was documented in eight patients with severe recurrence (44.4%), including three (37.5%) with biliary complications and two (7%) with non-severe recurrence, neither of whom had biliary complications (p=0.003). Antiviral treatment was successful in nine of 25 patients (36%) who received it. On multivariate analysis, biliary complications were a significant predictor of severe recurrence (OR 27.0, 95% confidence interval 2.07-351.4) (p=0.012). Fibrosis stage in the second biopsy was significantly correlated with serum alanine aminotransferase (p=0.01) and with duration of biliary obstruction (p=0.07). In conclusion, biliary complications of liver transplantation strongly affect outcome in patients with recurrent HCV disease despite attempts to relieve the biliary obstruction and to treat the recurrent HCV disease.

Adult↗