PubMed Health⌕ Search

Biomedical subjects

Anna Linda Zignego

Publications and source records attributed to Anna Linda Zignego.

10 recordsLinked to original sources
PubMed2006

Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin nonresponder patients.

BACKGROUND & AIMS: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. METHODS: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks. RESULTS: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). CONCLUSIONS: Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low gamma-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.

Adult↗
PubMed2005

Elevated Serum Levels of Osteopontin in HCV-Associated Lymphoproliferative Disorders.

Hepatitis C virus (HCV) infection is associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Recent evidences have also suggested that HCV infection contributes to development of autoimmune disorders and B-cell nonHodgkin's lymphoma (NHL). Mechanisms by which HCV infection promotes B-cell NHL development remain unclear. Increased serum osteopontin (OPN) levels have been associated with several autoimmune diseases as well as a variety of cancers. However, the association between OPN and B-cell NHL or HCV-associated B-cell proliferation has not previously been reported. In the present study, we determined whether serum OPN differences were associated with HCV infection, type II mixed cryglobulinemia (MC) syndrome and B-cell NHL. Serum OPN levels were measured by capture enzyme-linked immunosorbent assay. Our results show that high serum OPN levels are associated with B-cell NHL and HCV infection. Interestingly, highest serum OPN concentrations were found among HCV-infected patients with concomitant type II MC syndrome with and without B-cell NHL. These data indicate that OPN is involved in the lymphomagenesis, especially, in the context of HCV infection and autoimmune diseases.

Case-Control Studies↗
PubMed2004

Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients.

BACKGROUND: Mixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune complex deposition in the small vessels. In the overwhelming majority of patients, hepatitis C virus (HCV) infection represents the triggering factor of the disease. MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral nerves, and less frequently by widespread vasculitis and cancer. OBJECTIVES: To investigate the demographic, clinical, serologic features, and survival in a large series of MC patients. METHODS: The study included 231 MC patients recruited between 1972 and 2001 at the Rheumatology Unit of the University of Pisa. All patients underwent wide clinicoserologic and virologic assessment. Cumulative survival rates were computed by the Kaplan-Meier method; moreover, the prognostic relevance of the main variables was investigated by Cox model analysis. RESULTS: In 92% of cases, the presence of HCV infection was demonstrated (anti-HCV antibody, 92%; HCV RNA, 90%), whereas hepatitis B virus (HBV) represented the possible causative agent in only 1.8% of patients (HBV DNA). Clinically, the MC syndrome followed a relatively benign clinical course in over 50% of cases, whereas a moderate-severe clinical course was observed in one third of patients whose prognosis was severely affected by renal and/or liver failure. In a limited, but significant, percentage (15%) of individuals, the disease was complicated by a malignancy, ie, B-cell lymphoma, and less frequently by hepatocellular carcinoma, or thyroid cancer. The survival study by the Kaplan-Meier method revealed a significantly lower cumulative 10th-year survival, calculated from time of diagnosis, in MC patients compared with expected death in the age- and sex-matched general population. Moreover, significantly lower survival rates were observed in males and in subjects with renal involvement. The multivariate analysis by the Cox proportional hazard regression model further supported the above findings: an increased mortality risk of 98% was observed for male gender (male/female hazard ratio, 1.978) and of 197% in patients with, compared with those without, renal involvement (hazard ratio, 2.967). At the end of the follow-up, 97 patients were deceased, and in 79 of 97 patients, the causes of death were ascertained: nephropathy (33%), malignancies (23%), liver involvement (13%), and diffuse vasculitis (13%) were the most frequent causes of death. CONCLUSIONS: Careful patient monitoring is recommended for a timely diagnosis of life-threatening MC complications, mainly nephropathy, widespread vasculitis, and B-cell lymphoma or other malignancies.

Aged↗
PubMed2004

Detection of bcl-2 rearrangement in mucosa-associated lymphoid tissue lymphomas from patients with hepatitis C virus infection.

It has been shown that t(14;18)(q32;q21) involving fusion of IGH with MALT1 occurs frequently in mucosa-associated lymphoid tissue (MALT) lymphomas. Results of the present study indicate that the classical form of t(14;18)(q32;q21) involving fusion of IGH with bcl-2 can be detectable in a subset of MALT lymphomas in patients with hepatitis C virus (HCV) infection.

Adult↗
PubMed2003

Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.

Hepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B-cell lymphoproliferative disorders (LPDs). The t(14;18) translocation may play a pathogenetic role. Limited data are available regarding the effects of antiviral therapy on rearranged B-cell clones. We evaluated the effects of interferon and ribavirin on serum, B-lymphocyte HCV RNA, and t(14; 18) in 30 HCV+, t(14;18)+ patients without either mixed cryoglobulinemia syndrome or other LPDs. The t(14;18) translocation was analyzed by both bcl-2/JH polymerase chain reaction and bcl-2/JH junction sequencing in peripheral blood mononuclear cells in all patients. Fifteen untreated patients with comparable characteristics served as controls. Throughout the study, the presence or absence of both t(14;18) and HCV RNA sequences were, in most cases, associated in the same cell samples. At the end of treatment, t(14;18) was no longer detected in 15 patients (50%) with complete or partial virologic response, whereas it was persistently detected in nonresponders (P <.05), as well as in 14 of 15 control patients. In 4 responder patients, t(14;18) and HCV RNA sequences were no longer detected in blood cells after treatment, but were again detected after viral relapse; the same B-cell clones were involved in the pretreatment and posttreatment periods. In conclusion, this study suggests that antiviral therapy may induce regression of t(14;18)-bearing B-cell clones in HCV+ patients and that this phenomenon may be related, at least in part, to the antiviral effect of therapy. This in turn suggests that antiviral treatment may help prevent or treat HCV-related LPDs.

Alanine Transaminase↗
PubMed2002

Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas.

BACKGROUND: Hepatitis C virus (HCV) infection is strictly associated with mixed cryoglobulinemia, a benign B-cell lymphoproliferative disorder that may evolve to lymphoma. An increased prevalence of bcl-2 rearrangement (the t(14;18) translocation) has been shown in patients infected with HCV. OBJECTIVE: To evaluate the prevalence of bcl-2 rearrangement in patients with HCV-related mixed cryoglobulinemia and patients with chronic hepatitis but no cryoglobulinemia. DESIGN: Prospective study. SETTING: Two university hospitals. PATIENTS: 37 consecutively recruited patients with HCV-related mixed cryoglobulinemia and 101 patients with chronic HCV infection but without mixed cryoglobulinemia. MEASUREMENTS: Clinical and serologic characteristics; liver biopsy; bcl-2 rearrangement, Bcl-2 expression, and the ratio of Bcl-2 to Bax in total peripheral blood mononuclear cells and cell subgroups; and sequence analysis of the junction of bcl-2 and IgH joining segments in positive samples. RESULTS: Rearrangement of bcl-2 was observed in 28 of 37 (75.7%) patients with mixed cryoglobulinemia (65% of those with type III disease and 85% of those with type II disease, including 3 of 4 patients with lymphoma) and in 38 of 101 (37.6%) patients with chronic HCV infection but not mixed cryoglobulinemia (P < 0.001). Overexpression of Bcl-2 protein and a high ratio of Bcl-2 to Bax were observed in samples from patients with bcl-2 rearrangement. In 2 patients followed over time, peripheral blood cells bearing the t(14;18) translocation disappeared after antiviral therapy. CONCLUSIONS: Rearrangement of bcl-2 was found with increased frequency in patients with chronic HCV infection and mixed cryoglobulinemia. The frequency was greatest in patients with type II mixed cryoglobulinemia. The high ratio of Bcl-2 to Bax in patients with bcl-2 rearrangement and disappearance of the rearrangement with antiviral therapy suggest that the translocation is associated with the antiapoptotic function of Bcl-2 and that HCV infection is linked to inhibition of B-cell apoptosis.

Chromosomes, Human, Pair 14↗
PubMed2002

Hepatitis C virus core protein expression in human B-cell lines does not significantly modify main proliferative and apoptosis pathways.

Hepatitis C virus (HCV) chronic infection has been associated with many lymphoproliferative disorders. Several studies performed on hepatoma and fibroblast cell lines suggest a role of the HCV core protein in activation of cellular transduction pathways that lead to cell proliferation and inhibition of apoptosis. However, no data are available concerning the effects of HCV core expression on B-lymphocyte proliferation and apoptosis. B-lymphocyte cell lines permanently expressing full-length HCV 1b core sequences isolated from chronically infected patients were established using B-cell lines at different degrees of differentiation. Clones and pools of clones permanently expressing the HCV core were selected and characterized for protein expression by Western blot and FACS. Expression of HCV core proteins did not significantly enhance cell proliferation rates under normal culture conditions or under mitogenic stimulation. Analysis of NF-kappa B, CRE, TRE and SRE pathways by luciferase reporter genes did not show a significant influence of HCV core expression on these signal transduction cascades in B-lymphocytes. The effects of HCV core on anti-IgM and anti-FAS-induced apoptosis in B-cell lines was also analysed. In this experimental model, HCV core expression did not significantly modify the apoptotic profile of the B-lymphocyte cell lines tested. These data underline a cell type-specific effect of HCV core expression. In fact, it was not possible to show a significant contribution of the HCV core protein in activation of the major B-cell signal transduction pathways involved in the regulation of proliferation and programmed cell death, which is in contrast with the results reported in hepatoma cell lines.

Antibodies, Anti-Idiotypic↗