Pellicelli A.M.,Liver Unit |
Vignally P.,Instituto Superiore Sanita |
Messina V.,Infectious Disease |
Izzi A.,Infectious Disease |
And 20 more authors.
Annals of Hepatology | Year: 2014
Background and rationale of the study. Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. Results. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). Conclusions. Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeAgnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.
Ham C.,UK National Institute for Biological Standards and Control |
Srinivasan P.,Centers for Disease Control and Prevention |
Thorstensson R.,SIIDC |
Verschoor E.,BPRC |
And 6 more authors.
Journal of Clinical Microbiology | Year: 2010
An international multicenter study was conducted to assess the performance of a panel of simian immuno-deficiency virus (SIV) RNA reference materials for plasma viral load determinations. Reliable quantification was demonstrated across an ∼6 log10 dynamic range. Availability of external reference materials will enable independent calibration of SIV plasma viral load assays. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Ghinassi B.,Mount Sinai School of Medicine |
Ghinassi B.,University of Chieti Pescara |
Martelli F.,Instituto Superiore Sanita |
Verrucci M.,Instituto Superiore Sanita |
And 6 more authors.
Journal of Cellular Physiology | Year: 2010
The X-linked Gata1low mutation in mice induces strain-restricted myeloproliferative disorders characterized by extramedullary hematopoiesis in spleen (CD1 and DBA/2) and liver (CD1 only). To assess the role of the microenvironment in establishing this myeloproliferative trait, progenitor cell compartments of spleen and marrow from wild-type and Gata1low mice were compared. Phenotype and clonal assay of non-fractionated cells indicated that Gata1low mice contain progenitor cell numbers 4-fold lower and 10-fold higher than normal in marrow and spleen, respectively. However, progenitor cells prospectively isolated from spleen, but not from marrow, of Gata1low mice expressed colony-forming function in vitro. Therefore, calculation of cloning activity of purified cells demonstrated that the total number of Gata1low progenitor cells was 10- to 100-fold lower than normal in marrow and >1,000 times higher than normal in spleen. This observation indicates that Gata1low hematopoiesis is favored by the spleen and is in agreement with our previous report that removal of this organ induces wild-type hematopoiesis in heterozygous Gata1low/+ females (Migliaccio et al., 2009, Blood 114:2107). To clarify if rescue of wild-type hematopoiesis by splenectomy prevented extramedullary hematopoiesis in liver, marrow cytokine expression profile and liver histopathology of splenectomized Gata1low/+ females were investigated. After splenectomy, the marrow expression levels of TGF-β, VEGF, osteocalcin, PDGF-α, and SDF-1 remained abnormally high while Gata1low hematopoiesis was detectable in liver of both CD1 and DBA/2 mutants. Therefore, in the absence of the spleen, Gata1low hematopoiesis is supported by the liver suggesting that treatment of myelofibrosis in these animals requires the rescue of both stem cell and microenvironmental functions. © 2010 Wiley-Liss, Inc.