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Biomedical subjects

N Tassopoulos

Publications and source records attributed to N Tassopoulos.

At least 19 recordsLinked to original sources

Clinical significance of organ- and non-organ-specific autoantibodies on the response to anti-viral treatment of patients with chronic hepatitis C.

BACKGROUND: Development of organ- and non-organ-specific autoantibodies has been reported in hepatitis C virus patients treated with interferon-alpha plus/minus ribavirin. AIMS: To address whether prevalence and the titre of gastric parietal autoantibodies and non-organ-specific autoantibody in hepatitis C virus-treated patients were affected by therapy, and if the development of these antibodies carries any clinical significance on the response to treatment, as few studies in adults have been strictly designed to address the above hypothesis. METHODS: Samples at three time-points (baseline, end of treatment, end of follow-up) from 102 hepatitis C virus patients (39 sustained responders, 26 relapsers, 33 non-responders; four lost in follow-up) were studied for gastric parietal autoantibodies and/or non-organ-specific autoantibody by indirect immunofluorescence, commercial and in-house enzyme-linked immunosorbent assays. RESULTS: Sustained virological and biochemical response was associated with antinuclear antibody absence (end of treatment or end of follow-up), decrease of smooth-muscle antibody titres during therapy and gastric parietal autoantibodies negativity at baseline. However, after multivariate analysis only antinuclear antibody positivity at the end of treatment and increase of smooth-muscle antibody titres were associated with worst treatment response, independently of known factors of worst treatment outcome. CONCLUSIONS: We were able to demonstrate a negative correlation between the efficacy of anti-viral treatment for hepatitis C virus and the presence of antinuclear antibody and smooth-muscle antibody before treatment, or their increase during therapy.

Adult↗

Development and assessment of a novel real-time PCR assay for quantitation of HBV DNA.

HBV DNA quantitation is used extensively for the monitoring of treatment of hepatitis B virus (HBV) infection. The aim of this study was to develop a highly sensitive and reproducible real-time PCR (RTD-PCR) assay for the quantitation of HBV DNA using the LightCycler system. The performance of this assay was assessed by analyzing serial dilutions of HBV genomic DNA of known concentration and the lower limit of detection was found to be 1 DNA copy/reaction. By using serial dilutions of plasmid standard, RTD-PCR was determined to quantify HBV DNA in a 10-log10 dynamic range. RTD-PCR was found to be more sensitive than the commercially available tests such as the Quantiplex HBV DNA and the AMPLICOR HBV MONITOR assays. The median coefficient of variation of interexperimental variability was 3.2%. The HBV DNA values obtained with RTD-PCR were highly correlated with assays available commercially. These findings suggest that our RTD-PCR assay combines high sensitivity and reproducibility for HBV DNA quantitation in an incomparable high dynamic range of quantitation.

DNA, Viral↗

A phase II trial of oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma.

Only a minority of patients with hepatocellular carcinoma (HCC) may benefit from curative treatments, whereas there is no standard therapy for the remaining patients. The objective of this multicentre, open label phase II study was to estimate the objective tumour response rate of a 28-day regimen of oral eniluracil/5-fluorouracil (5-FU) in patients with chemotherapy-naïve, or anthracycline-refractory, inoperable HCC. 45 patients received courses of twice daily oral 5-FU (1.0 mg/m(2)) and eniluracil (10 mg/m(2)) for the first 28 days of each 5-week course. Patients were assessed at regular intervals to determine the tumour response and to evaluate toxicity. Patients were followed-up for a minimum of 6 months. No patient showed a partial or complete tumour response, and 18 patients (40%) had a best response of stable disease (95% confidence interval (CI) 25%, 55%). The median duration of progression-free survival (PFS) was 13.7 weeks (95% CI 10.0-20.0 weeks), and the median duration of overall survival (OS) was 50.3 weeks (range 1.1-64.1+ weeks). The combination of eniluracil/5-FU was well tolerated and had an acceptable safety profile. Only 7 patients (16%) reported at least one adverse event (AE) of grade 3 or 4 intensity considered reasonably attributable to the study medication. In conclusion, oral eniluracil/5-FU had minimal, if any, activity in patients with inoperable HCC, but the safety profile was acceptable.

Administration, Oral↗

A survey of bloodborne viruses and associated risk behaviours in Greek prisons.

AIMS: To determine HIV and hepatitis infection prevalence and correlates with risk behaviour. DESIGN: Cross-sectional study: voluntary, anonymous HIV, hepatitis (HCV, HBV and HDV) surveillance and questionnaire on risk factors. SETTING: Korydallos Prison, Athens and Ag. Stefanos Prison, Patra, Greece. PARTICIPANTS: Of 544 drug users imprisoned for drug related offences, all completed the questionnaire and 533 blood samples were collected. MEASUREMENTS: HIV (by anti-HIV-1), HCV (by anti-HCV), HBV (by anti-HBc, HBsAg) and HDV (by anti-HDV) prevalence. Data on demography, legal status, drug use, sharing of injecting equipment. FINDINGS: Of the 544 drug users, 375 (68.9%) had injected drugs (IDUs) at some time, 35% of whom had injected whilst in that prison. Of the 533 blood samples tested, one was positive for anti-HIV-1 (0.19%), 310 for anti-HCV (58.2%), 306/531 (57.6%) for anti-HBc, 34/527 (6.5%) for HBsAg and 12/527 (2.3%) for anti-HDV. Prevalence rates for IDUs only were 0.27% for HIV-1, 80.6% for hepatitis C, 62.7% for hepatitis B and 3.3% for hepatitis D. Ninety-two per cent of IDUs injecting in prison shared needles, indicating that IDUs inject less but share more during incarceration. Multiple logistic regression revealed needle-sharing as the most important risk factor for HCV infection in IDUs. Prior knowledge of a positive hepatitis result did not appear to inhibit IDUs from practising risky behaviours in prison. CONCLUSIONS: The epidemic of hepatitis B and C among imprisoned IDUs identified by this study constitutes a major public health problem. Prevention programmes, such as counselling, HBV vaccination, community-based methadone maintenance treatment and syringe exchange schemes, are necessary in order to prevent a further spread.

Adult↗

Prevalence patterns and genotypes of GB virus C/hepatitis G virus among imprisoned intravenous drug users.

An RT-PCR assay using primers from the 5'-UTR of the GBV-C/HGV genome was used to detect viremia, and a serological assay was used to detect past exposure to GBV-C/HGV, in sera from 106 imprisoned Greek intravenous drug users. High seroprevalence rates indicative of the parenteral route of transmission of the virus were found (32.1% for GBV-C RNA and 46.2% for anti-GBV-C E2). These rates were nonetheless lower in comparison to the corresponding rates of HCV infection markers (64.2% for HCV RNA and 77.4% for anti-HCV). Statistically significant univariate associations were observed between GBV-C-RNA positivity and younger age (P=0.006) and HCV-RNA positivity (P=0.024), as well as with higher serum alanine aminotransferase levels (P< 0.001); this latter association was shown to be independent of coinfection with HCV and of age by a multiple logistic regression model. Apparently, GBV-C/HGV had spread readily by needle-sharing in prison, while causing acute subclinical hepatitis in infected inmates. Phylogenetic analysis of the partial 5'-UTR of the GBV-C/HGV genome from 16 seropositive individuals, which delineated their grouping within genotype 2, also revealed a close genetic relationship between two sets of sequences from 4 drug addicts, 3 of whom admitted to sharing needles while imprisoned.

5' Untranslated Regions↗

A case-control study of hepatitis B and C virus infections in the etiology of hepatocellular carcinoma.

During a 16-month period in 1991-1992, blood samples and questionnaire data were obtained from 65 incident cases of hepatocellular carcinoma (HCC) as well as from 2 control groups of hospitalized patients matched on gender and age, which included 65 metastatic liver cancer (MLC) patients and 65 patients hospitalized for eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay. The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 18.8 (8.2-43.2) for the presence of HBsAg and 7.7 (1.7-35.1) for anti-HCV. In the present hospital-based case-control study anti-HCV testing was conducted on recently collected sera, using a second-generation enzyme immunoassay with confirmation by immunoblot assay. Comparisons with previous work in a similar population demonstrated that, when second-generation anti-HCV assays are applied to sera stored for 7-15 years, confirmatory assays or a higher diagnostic cut-off point may be necessary to ensure that the testing is specific.

Adult↗

HLA-associated non-responsiveness to hepatitis B vaccine.

HLA-A,B,DR antigens of two groups, one of normal individuals (N- = 31) and another of CRF (Chronic Renal Failure) patients (K- = 37), who did not develop anti-HBs protective antibodies after Hepatitis B (HB) vaccination, were compared, respectively, to the HLA antigens of two corresponding control groups (N+ = 52, K+ = 49), who responded to the vaccine. A statistically significant difference (Pc less than 0.02) in the frequency of HLA-DR3 was observed between responders and non-responders. An increased frequency of HLA-A1 and HLA-B8 in N- as well as of HLA-A1 and HLA-B35 in K- was also noticed, but this was not of statistical significance. As these antigens have been associated to both HBs antigenemia as well as chronic active hepatitis, we suggest that these genes or other genes in linkage to those may suppress the response to HBV vaccination while, in parallel, they may predispose to an autoimmune course of Hepatitis.

Female↗

Prevalence of HBV, HDV and HIV infections among intravenous drug addicts in Greece.

The prevalence of HBV, HDV and HIV infection was studied in 288 imprisoned intravenous drug addicts (IVDA) and 329 controls. Commercially available radioimmunoassays for the detection of HBV and HDV serologic markers and enzyme-immunoassays for IgM anti-HBc and anti-HIV were used. Anti-HIV positive results were confirmed by Western Blot. The prevalence of HBV serologic markers among IVDA (77.1%) was found considerably higher than among controls (22.5%). An increased prevalence of HBsAg carriers (6.9%) and anti-HBc alone positives (9.7%) was also found. IVDA carriers were more frequently HBeAg positive (25.0%) and HDV serologic markers were detected in 35.0% (7/20) of them. Anti-HIV were detected in 6 (2.1%) IVDA but in none control. These data show the widespread HBV and HDV infections among Greek IVDA and suggest the need for continuation of the initiated hepatitis B vaccination program. Anti-HIV prevalence is yet low. However there is urgent need for an extensive campaign to limit the further spread of the HIV among this high risk group.

Acquired Immunodeficiency Syndrome↗

Hepatitis delta virus infection.

The hepatitis delta virus (HDV) is a defective virus dependent for replication and infection on helper functions provided by the hepatitis B virus (HBV). HDV and HBV co-infection occurs mainly in acute hepatitis patients with frequent parenteral exposure such as intravenous drug addicts and transfused patients. In contrast, co-infection is very rare in patients with other sources of infection and usually is a self limited disease. HDV superinfection of HBsAg carriers may have a severe course and proceed to chronic active liver disease. Active immunoprophylaxis against HBV should be considered as the only preventive measure against HDV infection.

Hepatitis D↗

Evaluation of methods of pre-vaccination screening for markers of hepatitis B infection.

The prevalence of serologic evidence of hepatitis B virus infection in various populations in Greece was examined to provide data for formulating cost-effective strategies for prevaccination screening. Markers were detected in 17.5% of 320 healthy persons, 73.3% of 273 multiply transfused patients and 61.0% of 146 haemodialysis patients. In multiply transfused patients, antibody to hepatitis B surface antigen (anti-HBs) was significantly more common than antibody to core antigen (anti-HBc) (67.0%, 44.3%), while the opposite was true for haemodialysis patients (43.8%, 57.5%). These data suggest that it may be most cost-effective to screen only for anti-HBs in multiply transfused patients and only anti-HBc in haemodialysis patients. Vaccination without screening may be more cost-effective for healthy persons. Anti-HBs and anti-HBc were detected with similar frequencies (14.7%, 15.9%), thus neither offers an advantage in screening healthy persons, although use of anti-HBc may facilitate detection of chronic carriers. These data indicate that the choice of marker for pre-vaccination screening should depend on the population under consideration.

Adolescent↗

Post-exposure active immunoprophylaxis of spouses of acute viral hepatitis B patients.

Post-exposure efficacy of hepatitis B vaccine was evaluated in susceptible sexual partners of acute hepatitis B patients in a randomized double-blind, placebo-controlled trial in Greece. Vaccine (20 micrograms dose) or placebo was repeated one and six months after initial administration. Nine months' follow-up was completed by 146/160 entrants. Vaccinated (16.0%) and control spouses (18.3%) showed similar attack rates for all infections. The vaccine group had fewer clinical infections (2.7% against 7.0%) and fewer infections occurring more than one month after first vaccination (8.7% against 14.7%). These differences are not statistically significant, but suggest modification of infection. Overall, the attack rate was lower (p less than 0.01) for male spouses (6.4%) than for females (22.4%). It may be necessary to complement hepatitis B vaccination with hepatitis B immunoglobulin to protect this high-risk group.

Adult↗

Double infections with hepatitis A and B viruses.

Ten (2.8%) asymptomatic carriers of HBsAg and four (1.1%) patients with acute hepatitis B virus (HBV) infection were detected among 356 adults with acute viral hepatitis A (HAV) consecutively admitted to the Athens Hospital for Infectious Diseases from May 1981 to March 1984. These patients did not differ in clinical, epidemiologic (except in age), biochemical or serologic characteristics from patients acutely infected with HAV alone. Transient suppression of the HBV replication and disappearance of the HBV DNA accompanied by seroconversion from HBeAg positive to anti-HBe positive were detected in one and two carriers respectively. The titer of non-class-specific anti-HBc was low (less than or equal to 10(-2)) in all cases. These data suggest that superinfection of HBsAg carriers with HAV does not cause more severe disease or influence adversely the course of chronic hepatitis B disease. However, accurate diagnosis of double infections is necessary for prognosis of the liver disease and appropriate management of the patient's environment. This is quite important in areas with a high prevalence of HBV infections, like Greece, where double infections are relatively common.

Acute Disease↗