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Biomedical subjects

Caterina Pasquazzi

Publications and source records attributed to Caterina Pasquazzi.

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

Undetectable phospho-STAT1 in peripheral blood mononuclear cells from patients with chronic hepatitis C who do not respond to interferon-alpha therapy.

BACKGROUND: Recent studies have suggested that phosphorylated signal transducers and activators of transcription 1 (STAT1) plays an important role in interferon (IFN)-mediated biological functions, including antiviral activity. Moreover, it has been demonstrated that suppressors of the cytokine signal 1 (SOCS1) negatively regulates IFN activities. AIMS: To investigate the involvement of phospho-STAT1 in the response to IFN-alpha therapy in patients with chronic hepatitis C and to evaluate the negative regulatory effect of SOCS1 on STAT1 activation. METHODS: Sixty-five patients with chronic hepatitis C and 25 healthy subjects were enrolled. Twenty-five of the patients had never been treated with IFN-alpha therapy (naive), while the remaining 40 patients had. The IFN-treated patients were divided into sustained responders (SRs) or non-responders (NRs) on the basis of their response to the antiviral therapy. Peripheral blood mononuclear cells (PBMCs) were obtained from each patient and control, and were either stimulated with IFN-alpha or left unstimulated. Total STAT1, phospho-STAT1 and SOCS1 were revealed by means of Western blot. RESULTS: Total STAT1 was equally expressed in unstimulated and stimulated PBMCs from all patients and controls. One hundred percent of the stimulated PBMCs from healthy controls and SRs, 96% from naive subjects, and 30% from NRs showed detectable phospho-STAT1. By contrast, 70% of the stimulated PBMCs from NRs showed undetectable phospho-STAT1. CONCLUSIONS: We have demonstrated that phospho-STAT1 proteins in 70% of patients with chronic hepatitis C who do not respond to IFN treatment are undetectable, which suggests that this protein may be involved in the mediation of IFN sensitivity. The down-regulation of the Jak-STAT pathway because of SOCS1 expression may be one of the possible underlying mechanisms involved in resistance to IFN.

Adult↗
PubMed2005

Development of hepatotoxicity in HIV patients switching at least one protease inhibitor.

In order to evaluate the occurrence of hepatotoxicity in patients treated with antiretroviral therapy (ART) who switch protease inhibitor (PI), and the role of viral hepatitis in its development, we performed a retrospective study on 182 HIV patients treated with ART for 24 months. The presence of hepatitis viruses and alanine transaminase levels were evaluated. Hepatotoxicity developed in a low number of subjects without co-infection, but was significantly higher in co-infected patients (14/51 versus 62/131, P = 0.01). Ritonavir was associated with higher rates of severe hepatotoxicity in the co-infected group. Patients presenting any problems related to ART, including the development of hepatotoxicity, continued therapy by switching PI. The occurrence of hepatotoxicity with second/third choice PIs, including ritonavir, remained stable. Our results suggest that switching PI does not increase the occurrence of drug-related liver toxicity.

Adult↗
PubMed2004

Helicobacter pylori active infection in patients with acute coronary heart disease.

OBJECTIVES: To evaluate the possible role of the active Helicobacter pylori infection as a trigger factor in acute coronary heart disease (CHD). METHODS: Forty patients with acute coronary syndromes, 40 patients with infections other than H. pylori (control group A) and 40 healthy subjects (control group B), pair matched for age, sex and CHD risk factors were studied. In each patient and control subject the presence of H. pylori stool antigen (HpsA) and serum anti-CagA were tested. RESULTS: Twenty-eight of patients with CHD resulted positive for HpSA compared to 14 patients of control group A and 16 subjects of group B (p=0.00095). No significant difference was found in the anti-CagA positivity among patients with CHD and control groups. Concomitant positivity for anti-CagA and HpSA was found in 13 patients with CHD, four controls of group A and five controls of group B (p=0.017) CONCLUSIONS: Our findings revealed a higher rate of HpSA positivity and a significantly higher association between HpSA and anti-CagA positivity in patients with acute CHD compared to control groups. These data suggest that active H. pylori infection may play a role as a trigger factor in acute cardiovascular events.

Acute Disease↗
PubMed2004

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: the role of serum aspartate transaminase in the evaluation of disease progression.

OBJECTIVES: To investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage. METHODS: We performed a retrospective study on 112 patients with chronic hepatitis C. For each patient, we considered the baseline alanine aminotransferase (ALT) and serum aspartate transaminase (AST) levels, baseline HCV RNA, HCV genotype, histological evaluation and the mean aminotransferase levels measured in the 6 months following liver biopsy. RESULTS: We found a statistically significant correlation between HCV RNA and aminotransferase levels measured during the follow-up (AST: r = 0.24, P = 0.01; ALT: r = 0.27, P = 0.004). We also observed a statistically significant correlation between HCV RNA levels and histological activity index (HAI) (r = 0.25, P = 0.008), as well as between the HAI and both baseline AST (r = 0.34, P = 0.0002) and ALT levels (r = 0.23, P = 0.01). These findings were confirmed by the mean aminotransferase values during follow-up. In the regression analysis, the fibrosis score was significantly and independently associated with baseline AST and ALT values. CONCLUSIONS: Our results demonstrate a statistically significant correlation of aminotransferase values with the histological parameters, and an even stronger correlation with the AST values. Our study therefore suggests that aminotransferase values, especially AST, may correlate with liver damage.

Adult↗
PubMed2003

Antibody-selected mimics of hepatitis C virus hypervariable region 1 activate both primary and memory Th lymphocytes.

An ideal strategy that leads to a vaccine aimed at controlling viral escape may be that of preventing the replication of escape mutants by eliciting a T- and B-cell repertoire directed against many viral variants. The hypervariable region 1 (HVR1) of the putative envelope 2 protein that presents B and T epitopes shown to induce protective immunity against hepatitis C virus (HCV), might be suitable for this purpose if its immunogenicity can be improved by generating mimics that induce broad, highly cross-reactive, anti-HVR1 responses. Recently we described a successful approach to select HVR1 mimics (mimotopes) incorporating the variability found in a great number of viral variants. In this report we explore whether these mimotopes, designed to mimic B-cell epitopes, also mimic helper T-cell epitopes. The first interesting observation is that mimotopes selected for their reactivity to HVR1-specific antibodies of infected patients also do express HVR1 T-cell epitopes, suggesting that similar constraints govern HVR1-specific humoral and cellular immune responses. Moreover, some HVR1 mimotopes stimulate a multispecific CD4(+) T-cell repertoire that effectively cross-reacts with HVR1 native sequences. This may significantly limit effects as a T-cell receptor (TCR) antagonist frequently exerted by natural HVR1-variants on HVR1-specific T-cell responses. In conclusion, these data lend strong support to using HVR1 mimotopes in vaccines designed to prevent replication of escape mutants.

Adult↗
PubMed2002

Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection.

To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV-infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection.

Adult↗
PubMed2002

Serum concentration of gammaGT is a surrogate marker of hepatic TNF-alpha mRNA expression in chronic hepatitis C.

Serum gammaGT levels and hepatic expression of tumor necrosis factor-alpha (TNF-alpha) are host factors that can independently predict the outcome of interferon (IFN) treatment in patients with chronic hepatitis C virus (HCV) infection. To explore whether a correlation exists between these two factors, we measured pretreatment gammaGT levels in serum and TNF-alpha mRNA levels in liver biopsies of chronic HCV patients. Seventy-two HCV patients treated with 3-to-5 million units of IFN-alpha three times a week were enrolled in the study. Treatment lasted 24 weeks and was followed by a 48-week follow-up period. Efficacy was assessed by measuring HCV RNA and alanine aminotransferase by the end of follow-up. Twelve patients (16.6%) showed a sustained biochemical and virological response. Normal pretreatment gammaGT levels, low HCV RNA titer, and infection with genotype other than HCV-1 were shown to be independent predictors of sustained response. Hepatic levels of TNF-alpha mRNA, quantified by polymerase chain reaction, were significantly higher in nonresponders (3.44 arbitrary units) compared to sustained responders (1.84 arbitrary units; P = 0.009). Values </=3.12 arbitrary units independently predicted a sustained response to IFN (P = 0.014). Finally, TNF-alpha mRNA levels were significantly correlated with serum gammaGT levels (r = 0.79, P < 0.0001). These findings suggest that serum gammaGT levels may represent a surrogate marker of hepatic TNF-alpha expression, thus explaining the importance of serum gammaGT levels in predicting treatment outcome.

Adult↗