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Biomedical subjects

A Hatzakis

Publications and source records attributed to A Hatzakis.

At least 73 records · Page 4Linked to original sources

Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen.

BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, may be the infectious cause of KS. Its prevalence in the general population, on the basis of detection of the virus genome, is controversial. To investigate the seroprevalence, we measured antibodies to a recombinant capsid-related (lytic cycle) KSHV antigen and a latent antigen complex. METHODS: We selected potentially immunoreactive capsid-related proteins of KSHV by expressing them as recombinant proteins and testing them in western blot assays. We used a truncated recombinant protein encoded by KSHV open reading frame 65 (orf 65) to develop a diagnostic enzyme-linked immunosorbent assay (ELISA) and tested sera from HIV-infected individuals with KS, HIV-uninfected patients with "classic" KS, other HIV risk groups, and blood donors. We also compared the antibody response to this capsid-related protein to the response to latent antigen(s) in an immunofluorescence assay. FINDINGS: 77/92 (84%) sera from KS patients reacted with the KSHV orf 65 protein and 84/103 (81.5%) reacted with KSHV latent antigen(s). The dominant immunogenic region of orf 65 is within the carboxyterminal 80 aminoacids, a region with little sequence similarity to the related Epstein-Barr virus, suggesting that orf 65 is a KSHV specific antigen. Only three sera from patients with haemophilia (1/84) or from intravenous drug users (2/63) had KSHV specific antibodies in the orf 65 assay whereas none of these sera reacted with latent antigen. Antibodies to KSHV were also infrequently found in UK and US blood donors by either assay (UK, 3/174 with orf 65 and 4/150 with latent antigen; US, 6/117 with orf 65 and 0/117 with latent antigen). They were more common among HIV-infected gay men without KS (5/16 by orf 65 ELISA, 10/33 by IFA), HIV-uninfected STD clinic attenders (14/166 by IFA), and Ugandan HIV-uninfected controls (6/17 by orf 65 ELISA, 9/17 by IFA). Antibody reactivity to the orf 65 protein (ELISA) and to latent antigen(s) (IFA) was concordant in 89% of 462 sera tested but reactive blood donor sera were discordant in both assays. Four AIDS-KS sera were unreactive in both assays. INTERPRETATION: The distribution of antibodies to both a capsid-related recombinant protein and latent antigen(s) of KSHV strongly supports the view that infection with this virus is largely confined to individuals with, or at increased risk for, KS. However, infection with KSHV does occur, rarely, in the general UK and US population and is more common in Uganda. Antibodies to latent antigen(s) or to orf 65 encoded capsid protein will not detect all cases of KSHV infection, and a combination of several antigens will probably be required for accurate screening and confirmatory assays.

Adult↗

Hepatitis C virus 1b is the dominant genotype in HCV-related carcinogenesis: a case-control study.

In an ongoing case-control study in Athens on the etiology of hepatocellular carcinoma (HCC), an analysis was made in order to assess whether HCV genotype 1b is associated with hepatocellular carcinoma (HCC). The HCV genotype was determined in 17 HCC patients, 87 patients with chronic hepatitis C (CHC) without cirrhosis (NC-CHC) and 23 patients with CHC and cirrhosis (C-CHC). HCV genotype 1b was detected in 14/17, 16/23 and 23/87 of HCC, C-CHC and NC-CHC respectively. The age- and gender-adjusted odds ratios contrasting HCC with NC-CHC and C-CHC with NC-CHC were 8.3 and 3.8 respectively. These data strongly support the hypothesis that HCV 1b is a stronger liver carcinogen than other HCV genotypes, probably through increased HCV replication and enhanced liver cytopathicity.

Adult↗

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study.

OBJECTIVE: To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. DESIGN: Epidemiologic cohort study. SETTING: Five hemophilia treatment centers in the United States. SUBJECTS: A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. METHODS: The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. RESULTS: The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12069 copies/mL) (P = .02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100,000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n = 9), 52% among subjects with 10,000 to 99,999 copies/mL (n = 55), 22% among subjects with 1000 to 9,999 copies/mL (n = 82), and 0% among subjects with fewer than 1000 copies/mL (n = 19) (P < .001). The age-adjusted relative hazard for AIDS for subjects with 10,000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL. CONCLUSIONS: The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low levels define persons with a high probability of long-term AIDS-free survival.

Acquired Immunodeficiency Syndrome↗

Herpesvirus-like DNA sequences detected in endemic, classic, iatrogenic and epidemic Kaposi's sarcoma (KS) biopsies.

The identification of Kaposi's sarcoma (KS) clusters in sub-equatorial Africa (endemic KS, AKS) and the high frequency of KS in sexually transmitted AIDS (epidemic KS, EKS), have previously suggested a role for infectious agents in the etiopathogenesis of KS. The recent identification of herpesvirus (HHV)-like DNA sequences in one case of EKS and their detection in > 90% of all tested EKS, prompted us to determine the prevalence of these viral sequences in all types of KS, such as AKS, EKS, classic KS (CKS) and iatrogenic KS (IKS). The presence of herpesvirus(HHV)-like DNA sequences has been examined in 61 KS skin tumors obtained from Greece, Italy, USA, Uganda and Kenya. All KS types (100%) were positive by polymerase chain reaction (PCR) and Southern-blot analysis, while 5 out of 6 (83%) and 4 out of 7 (57%) uninvolved autologous skin biopsies from AKS and CKS patients, respectively, were positive for HHV-like sequences. All samples from non-KS patients were negative, i.e. 17 human biopsies from healthy individuals or patients affected by other pathologies, 5 human cell lines and 15 peripheral blood mononuclear cells (PBMC) from HIV-positive subjects. These results suggest that HHV-like sequences play a major role in the pathogenesis of this neoplasm.

DNA, Viral↗

Prevalence study of different hepatitis markers among pregnant Albanian refugees in Greece.

Aim of the study was to record the prevalence of the various types of viral hepatitis, especially hepatitis B, in pregnant Albanian refugees in Greece. The study comprised 500 pregnant refugees of mean age 25.1 +/- 4.6 years. In Albania, all women had lived in overcrowded houses and had been exposed to non throw-away needles and syringes. Various indices for all hepatitis types were determined. The prevalence of HBsAg was 13.4%, of anti-HBs 53%, of total anti-HBc 70.8%, of anti-HBc IgM 0.4%, of HBeAg 1.2%, of anti-HBe 58.6%, of anti-HAV 96.2%, of anti-HAV IgM 1%, of anti-HDV 0.4%, of anti-HCV 0.6% and of anti-HEV 2%. HBeAg was found positive in 7.5% of HBsAg carriers. Prevalence of hepatitis B markers, as determined by HBsAg and/or anti-HBs and/or total anti-HBc was significantly higher in those with a history of previous hospitalization in Albania (p = 0.01) and those with previous history of hepatitis (p = 0.02). The high prevalence of hepatitis B markers in pregnant Albanian refugees proves that HBV infection is highly endemic in Albania and the possibility of perinatal transmission to the offsprings urges for HBV vaccination programmes. On the other hand improvements in the socioeconomic conditions and the sanitation system in Albania is anticipated to reduce the incidence of HAV and HBV infections.

Adolescent↗

Hepatitis E virus infection in individuals at high risk of transmission of non-A, non-B hepatitis and sexually transmitted diseases.

The aim of the study was to determine the prevalence of hepatitis E virus (HEV) infection among individuals at high risk of transmission of non-A, non-B hepatitis or sexually transmitted diseases (STDs), and to evaluate whether they have an increased risk of exposure to HEV. Serum samples from 125 thalassemia patients, 300 intravenous drug users, 420 hemodialysis patients, 263 individuals with STDs, 47 human immunodeficiency virus (HIV) infected homosexual men, and 316 healthy volunteers were tested for immunoglobulin G (IgG) and M (IgM) antibodies to HEV (anti-HEV) by enzyme immunoassays (EIAs) following a predetermined algorithm (Abbott Labs). Anti-HEV IgG was confirmed in 3/125 (2.4%) thalassemia patients, 5/300 (1.7%) intravenous drug users, 27/420 (6.4%) hemodialysis patients, 4/263 (1.5%) STD patients, 1/47 (2.1%) homosexual men, and 7/316 (2.2%) of the reference group. No patient was found positive for anti-HEV IgM. The higher prevalence which was observed in hemodialysis group was due to the confounding effect of age, as multivariate analysis showed. The anti-HEV prevalence increased significantly with age (p = 10(-4)). No significant association was found between anti-HEV, anti-HCV, and anti-HBc. In conclusion, individuals at high risk of non-A, non-B hepatitis and STDs have no increased risk of exposure to HEV and the higher prevalence of anti-HEV IgG among older subjects may be due to an epidemic form of HEV infection which occurred some decades ago, when the sanitary conditions in our country were poor.

Adolescent↗

Hepatitis E virus (HEV) infection in haemodialysis patients. The Multicentre Haemodialysis Cohort Study on Viral Hepatitis.

BACKGROUND: The aim of this study was to determine the prevalence of hepatitis E virus (HEV) infection among patients undergoing haemodialysis (HD) and to evaluate whether chronic haemodialysis is associated with an increased risk of HEV infection. METHODS: Serum samples from 420 HD patients and 316 healthy volunteers were tested for IgG and IgM antibodies to HEV (anti-HEV). Anti-HEV IgG positive sera were confirmed using synthetic peptides. RESULTS: Anti-HEV IgG was confirmed in 27/420 (6.4%) of the HD patients and in 7/316 (2. 2%) of the reference group (P=0.07). However, multiple logistic regression analysis showed that the prevalence of anti-HEV IgG was not significantly higher in HD patients compared with the reference group, after controlling for age and sex. No patient was found positive for anti-HEV IgM. The presence of anti-HEV was associated with sex in HD patients (P=0.04). No significant association was found between anti-HEV and underlying renal disease, anti-HCV, anti-HBc, blood transfusions, history of elevated transaminases, history of clinical hepatitis and renal transplantation. A marginal association, which was observed with the duration of haemodialysis in univariate analysis (P=0.07), was not confirmed in multivariate analysis. CONCLUSIONS: Chronic haemodialysis is not associated with an increased risk of exposure to HEV, and the high prevalence of anti-HEV IgG in HD patients reported in uncontrolled studies is possibly due to the confounding effect of age and sex.

Adolescent↗

Comparative efficacy of a high or low dose of interferon alpha 2b in chronic hepatitis C: a randomized controlled trial.

OBJECTIVES: Our objective was to determine the relative efficacy of 6 months of treatment with 10 MU versus 3 MU of interferon-alpha 2b (IFN-alpha), three times weekly, in chronic hepatitis C (HCV) in a randomized trial. METHODS: Ten megaunits of IFN-alpha were given to 28 patients (group A), and 3 MU were given to 30 patients (group B). After treatment ended, follow-up was continued for 26 wk. RESULTS: Overall, the sustained response rate was higher in group A than in group B (16/26 or 61.5% vs. 12/28 or 42.9%, p = 0.17), but the difference did not reach statistical significance. However, it was higher in group A than in group B among patients with minimal or mild chronic hepatitis (15/20 or 75% vs. 9/24 or 37.5%, p = 0.013) and among those with mild or moderate fibrosis (15/17 or 88.2% vs. 11/19 or 57.9%, p = 0.042). IFN-alpha treatment significantly reduced histological activity index (HAI) scoring and all its parameters, except fibrosis, but the decrease was similar in the two groups. Sex, age, stage, and HCV genotype were statistically significant predictors of sustained response in univariate analysis. However, multiple logistic regression analysis revealed that advanced histological stage (severe fibrosis and cirrhosis) was the only significant prognostic factor of poor sustained response (RR = 31.0, 95% CI 2-460, p = 0.01), whereas the presence of genotype 1 had marginal statistical significance (RR = 5.0, 95% CI 0.9-28, p = 0.07). CONCLUSIONS: 1) A larger dose of IFN-alpha does not improve the sustained response rate; however, it may be of benefit in early stages of chronic hepatitis C. 2) Pretreatment, histological stage, and possibly HCV genotype appear to be the main prognostic factors of sustained response.

Adult↗

Biochemical and virological response of chronic hepatitis C after treatment with interferon-alpha for 6 or 12 months: predictors of sustained remission.

OBJECTIVE: To evaluate the biochemical and virological response in chronic hepatitis C patients treated with interferon-alpha at the usual dosage of 3 MU thrice weekly for 6 or 12 months, and to analyse the significance of clearance of serum HCV RNA and of HCV genotype in the prediction of sustained biochemical remission. SETTING: Liver Unit, Western Attica General Hospital, Athens, Greece. PARTICIPANTS: Sixty consecutive patients with histologically confirmed chronic hepatitis C. INTERVENTIONS: All patients received interferon-alpha-2b in a dose of 3 MU thrice weekly for 6 (n = 26) or 12 (n = 34) months. Serial serum samples were retrospectively tested for the presence of HCV RNA by a polymerase chain reaction assay and pretreatment serum samples for the determination of HCV genotype. RESULTS: Sustained biochemical response rate was significantly higher in the 12-month group (62% vs. 35%, P = 0.037). Clearance of serum HCV RNA at the end of treatment was achieved in 33 (58.9%) of the 56 patients with detectable pretreatment HCV RNA. HCV RNA reappeared in serum significantly more often in patients treated for 6 than for 12 months (35.7% vs. 5.3%, P = 0.037). Serum HCV RNA after 6 months of therapy was a prognostic factor of sustained biochemical response, which was observed in 75% of the HCV RNA-negative and in only 16.7% of the HCV RNA-positive patients (OR 0.067, P < 0.001). Moreover, in patients negative for HCV RNA after 6 months of therapy, 12 months' treatment resulted in a higher sustained response rate than did 6 months' (89% vs. 57%, P = 0.05). HCV genotype 1 was associated with a significantly lower sustained response rate (30% vs. 60.7%, P = 0.035), whereas 12 months' treatment induced sustained remission significantly more often only in patients with genotype 1 (6/12 vs. 0/8, P = 0.024). CONCLUSION: In chronic hepatitis C treatment HCV genotype and serum HCV RNA after 6 months of therapy are strong predictive factors of a sustained response, and a 12-month rather than a 6-month interferon regimen may induce a more persistent clearance of HCV RNA in total and a higher sustained response rate in patients with HCV genotype 1 and in those who clear HCV RNA after 6 months of therapy.

Adult↗

Hepatitis E virus infection in a cohort of patients with acute non-A, non-B hepatitis.

BACKGROUND/AIMS: The aim of this study was to determine the frequency of hepatitis E virus infection in a cohort of patients with acute non-A, non-B hepatitis in Greece. METHODS: Serial serum samples of 198 patients with acute non-A, non-B hepatitis and a single serum specimen from 316 healthy subjects were tested for IgG and IgM antibodies to hepatitis E virus (anti-HEV). RESULTS: Anti-HEV IgG was found in 15/198 (7.6%) of acute non-A, non-B hepatitis patients and 7/316 (2.2%) of healthy controls (p=0.007). Anti-HEV IgM was found in 2/198 (1.0%) acute non-A, non-B hepatitis patients and in none of the healthy subjects. Neither anti-HEV IgM (+) case reported any risk factor and neither had travelled in areas endemic for hepatitis E virus infection. HEV-RNA was detected by reverse transcription polymerase chain reaction in one patient. The prevalence of anti-HEV IgG was 7/45 (15.6%), 1/46 (2.2%), 5/30 (16.7%) and 2/77 (2.6%) in acute non-A, non-B hepatitis reporting transfusion, intravenous drug use, occupational/hospitalization, and unknown transmission, respectively (p=0.007). Anti-HEV IgG was found in 13/122 (10.7%) and 2/76 (2.6%) of acute non-A, non-B hepatitis patients positive and negative for anti-HCV, respectively (p=0.03). A similar association was found with anti-HBc (p=0.007). The prevalence of anti-HEV IgG was significantly higher in cases reporting transfusion [OR=7.3, 95% C.I. 1.4-37.7, p=0.017] and occupational/hospitalization [OR=6.8, 95% C.I. 1.2-38.2, p=0.029], as transmission category after controlling for age. CONCLUSIONS: These findings indicate that: (a) hepatitis E virus may be a cause - although not a frequent one - of sporadic or community-acquired acute non-A, non-B hepatitis in Greece; (b) hepatitis E virus may share transmission routes with hepatitis B and C viruses; and (c) the hypothesis that hepatitis E virus may be transmitted by parenteral routes deserves careful consideration.

Acute Disease↗

Histological and functional changes in the salivary glands in thalassaemia major.

Oral salivary secretion and oral histology in 15 multi-transfused adult thalassaemia homozygotes was studied. Iron stores of minor salivary glands were also histochemically determined. Salivary secretion in multi-transfused thalassaemia patients was subclinically decreased, but no clear correlation was evident between salivary secretion impairment and salivary gland destruction by iron deposition, lymphocyte infiltration and fibrosis. The underlying mechanism remains to be determined.

Adolescent↗

Clinicopathological assessment of hepatitis C virus infection in parenteral drug abusers.

OBJECTIVES: To determine the severity of hepatic histological lesions in anti-HCV positive parenteral drug abusers and to correlate it with the level of ALT activity and HCV RNA determined by polymerase chain reaction (PCR). METHODS: Twenty-nine of the 62 anti-HCV-positive parenteral drug abusers who consecutively entered a Rehabilitation Center of Athens consented to liver biopsy and were prospectively and thoroughly followed up for a mean of 12.9 (range 6-33) months. Anti-HCV was detected by a second-generation enzyme immunoassay and confirmed by a second-generation recombinant immunoblot assay. Serum samples were tested for HCV RNA by nested PCR with primers from the highly conserved 5' untranslated region of the HCV genome. RESULTS: Liver biopsy revealed lesions compatible with chronic hepatitis in 26 (89.6%) and a normal liver in three (10.4%) of the 29 patients. In particular, 11 (37.9%) had minimal and 15 (57.1%) had mild chronic hepatitis; fibrosis was absent or mild in all cases. Histological grade and stage were significantly milder in patients with persistently normal ALT activity than in those with increased ALT activity. However, chronic hepatitis was observed in five (62.5%) of the eight patients with normal ALT levels. The presence of serum HCV RNA was not significantly correlated with the severity of histological lesions. HCV RNA was detected in 16 (57.1%) of the 28 cases tested. In particular, HCV RNA was detected in one (33.3%) of the three cases with normal liver and in three (37.5%) of the eight patients with normal ALT levels. CONCLUSIONS: Liver biopsy appears to be the method of choice for the accurate evaluation of anti-HCV positive parenteral drug abusers, irrespective of ALT activity and presence of serum HCV RNA. Chronic hepatitis is observed in the majority and the state of "healthy" carrier of HCV in the minority of this epidemiological setting.

Adult↗

Case report: role of hepatitis E virus in the etiology of community-acquired non-A, non-B hepatitis in Greece.

The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries.

Adolescent↗

Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus-infected hemophilia patients. National Cancer Institute Multicenter Hemophilia Cohort Study Group.

The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors.

Acquired Immunodeficiency Syndrome↗