HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece.

The current study investigated the impact of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection on the rate of change of antiretroviral drugs after the initiation of highly active antiretroviral treatment (HAART). The data on 1425 HIV-positive patients with recorded serology for hepatitis B surface antigen (HBsAg) were retrospectively analysed. The estimated rate of treatment change was slightly higher in the HBsAg-positive group (0.57 per year) compared with the HBsAg-negative group (0.50 per year). Although this difference was insignificant in multivariable modelling, the confidence intervals of the estimates barely included unity. Antiretroviral drug family, calendar period, prior exposure to antiretrovirals and the diagnosis of acquired immunodeficiency syndrome were independently associated with the number of drug alterations. A slight impact of co-infection on the frequency of treatment change after the beginning of HAART cannot be excluded. However, the paucity of studies on this issue necessitates the conduct of further research.

Consumption of dairy products in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: data from 35 955 24-hour dietary recalls in 10 European countries.

OBJECTIVES: To describe and compare the consumption of dairy products in cohorts included in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Data from single 24-hour dietary recall interviews collected through a highly standardised computer-based program (EPIC-SOFT) in 27 redefined centres in 10 European countries between 1995 and 2000. From a total random sample of 36 900, 22 924 women and 13 031 men were selected after exclusion of subjects under 35 and over 74 years of age. RESULTS: A high total consumption of dairy products was reported in most of the centres in Spain and in the UK cohort sampled from the general population, as well as in the Dutch, Swedish and Danish centres. A somewhat low consumption was reported in the Greek centre and in some of the Italian centres (Ragusa and Turin). In all centres and for both sexes, milk constituted the dairy sub-group with the largest proportion (in grams) of total dairy consumption, followed by yoghurt and other fermented milk products, and cheese. Still, there was a wide range in the contributions of the different dairy sub-groups between centres. The Spanish and Nordic centres generally reported a high consumption of milk, the Swedish and Dutch centres reported a high consumption of yoghurt and other fermented milk products, whereas the highest consumption of cheese was reported in the French centres. CONCLUSION: The results demonstrate both quantitative and qualitative disparities in dairy product consumption among the EPIC centres. This offers a sound starting point for analyses of associations between dairy intake and chronic diseases such as cancer.

Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study.

OBJECTIVE: To describe and compare the consumption of total fish (marine foods) and the fish sub-groups - white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study. DESIGN: Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender. SETTING: Twenty-seven redefined centres in the 10 European countries participating in the EPIC study. SUBJECTS: In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, selected from the main EPIC cohort. RESULTS: A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake. CONCLUSIONS: Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.

Birth order, as a proxy for age at infection, in the etiology of hepatocellular carcinoma.

First-born and second-born children are exposed to common infections after enrollment at school, whereas later-born children are exposed to these infections earlier through their older siblings. We have evaluated whether birth order is a risk factor for hepatitis B virus (HBV)-related, hepatitis C virus (HCV)-related, and apparently virus-unrelated hepatocellular carcinoma (HCC) in a large case-control study that included 333 HCC cases and 632 controls. In comparison with controls who were carriers of hepatitis B surface antigen (HBsAg), HBsAg-positive HCC cases were more likely to have been later-born children (odds ratio per increase in birth order = 2.0; 95% confidence interval = 1.2-3.6). There was no such evidence for anti-HCV-positive cases compared with anti-HCV-positive controls or for virus-negative HCC cases compared with virus-negative controls. We conclude that early infection with HBV increases the risk of HBV carriers to develop HCC, over and beyond its role in facilitating the establishment of a carrier state.

Total cholesterol and HDL-cholesterol in relation to socioeconomic status in a sample of 11,645 Greek adults: the EPIC study in Greece. European Prospective Investigation into Nutrition and Cancer.

OBJECTIVE: To examine the relationship between educational level, a powerful indicator of socioeconomic status in Greece, total cholesterol and HDL-cholesterol in a large sample of Greek adults. METHODS: The study sample consisted of 11,645 subjects, 4,398 men and 7,247 women, aged 23-86 years, who voluntarily participated in the Greek component of the EPIC study during 1994-98. Educational attainment was divided into low, medium, and high. Linear regression analyses were performed, in men and women separately, using total and HDL-cholesterol as dependent variables and educational level as independent, while controlling for age. RESULTS: Total blood cholesterol values are inversely associated with educational level in both genders, a pattern contrasting with that found 20 years ago. The association is more prominent among women. HDL-cholesterol values are inversely associated with educational level in men, whereas the association is less consistent in women.

The epidemiology of benign prostatic hyperplasia: a study in Greece.

OBJECTIVE: To assess the epidemiology of benign prostatic hyperplasia (BPH) in a case-control study in greater Athens, Greece. PATIENTS AND METHODS: The study comprised 184 patients surgically treated for BPH within one year of its diagnosis (cases) and 246 patients with no symptoms of BPH who were treated in the same hospitals for minor diseases or conditions (controls). All cases and controls were permanent residents of the greater Athens area, Greece. The data were assessed using unconditional logistic regression. RESULTS: After controlling for age and education, cases and controls had similar distributions for height, body mass index, sibship size and birth order in the parental family, marital status, number of offspring and a series of previous medical diagnoses or surgical operations. The sole exception was surgery for haemorrhoids, that appeared to be related to the incidence of BPH, possibly by chance. There was no evidence that vertex baldness, tobacco smoking, alcohol consumption or coffee drinking increased the risk for BPH. Men who had spent most of their lives in a rural rather than an urban environment appeared to be at reduced risk for BPH. CONCLUSION: The lifestyle factors assessed here have no major effect on the aetiology of BPH.

Adolescents in high-risk trajectory: clustering of risky behavior and the origins of socioeconomic health differentials.

BACKGROUND: We have evaluated high-risk behavior of adolescents 12 to 17 years of age on the basis of seven binomial psychosocial variables in order to assess whether there is a tendency of these variables to cluster in the same individuals and to identify socioeconomic covariates of risky behavior. METHODS: Study participants were 547 adolescents from four high schools in Greece: two in rural areas, one in an upper-medium socioeconomic class areas, and one in a low-to-medium socioeconomic class area of Athens. Clustering was assessed by evaluating concordance of high-risk attributes examined in pairs, and was expressed as a series of odds ratios (ORs) as well as by factor analysis. RESULTS: All but one OR were higher than the null value, but they were particularly high with respect to smoking and nonuse of safety belts (OR = 3.2, P < 10(-4)), smoking and binge drinking (OR = 3.3, P < 10(-4)), smoking and riding with a drunk driver (OR = 5.3, P = 10(-4)), smoking and driving under the influence of alcohol (OR = 9.7, P < 10(-4)), nonuse of oral contraceptives and riding a car with a drunk driver (OR = 15.4, P = 0.002), and driving under the influence of alcohol and riding with a drunk driver (OR = 18.6, P < 10(-4)). Factor analysis indicated that risky behavior could be explained in terms of two component factors, namely carelessness in the context of self interest and irresponsible sexual behavior. A composite index integrating information of all seven high-risk indicators regressed on sociodemographic characteristics showed that risky behavior increased sharply with age and was concentrated strongly in the low-education families and the lower income areas. CONCLUSIONS: Several aspects of high-risk behavior tend to aggregate in the same individuals, and the clustering pattern has already been developed by late adolescence, mostly among the less privileged families and population groups. It appears that socioeconomic class health differentials may have strong roots in late adolescence.

Determinants of age at menarche as early life predictors of breast cancer risk.

Age at menarche is one of the few established risk factors for breast cancer; identification of its exogenous determinants could throw light on the origins of breast cancer. We have undertaken an epidemiologic study in Greece to ascertain whether: 1) energy intake, an indicator of physical activity, is associated with later age at menarche; 2) energy-adjusted fat intake is related to earlier age at menarche; and 3) other macronutrients and anthropometric variables are predictors of age at menarche. Anthropometric, socio-economic, familiar, nutritional and lifestyle predictors of age at menarche were studied by interviewing in person 345 female students 9 to 16 years old attending 8 schools of Greater Athens. Menarche was the outcome variable in a proportional hazards model assessing the mutually adjusted incidence rate ratio by a series of predictor variables. In a complementary analysis, age at menarche was the dependent variable among menstruating girls. Consistent results were derived from the main and the complementary analysis. Increased height and body mass index accelerate the occurrence of menarche. Maternal and daughter's ages at menarche are correlated, but there is no evidence of an association with paternal education. Various measures of moderate physical activity as well as increased total energy intake were associated with a delay in age at menarche. Energy-adjusted macronutrients were not associated with age at menarche. It appears that an alteration of energy balance in early life through increased physical activity could delay age at menarche and reduce the risk for breast cancer in later life.

Age at first establishment of chronic hepatitis B virus infection and hepatocellular carcinoma risk. A birth order study.

It is frequently assumed that the risk of hepatocellular carcinoma related to hepatitis B virus is higher when chronic hepatitis B virus infection is acquired early in life. This hypothesis has never been directly evaluated. However, firstborn and secondborn children are exposed to common infections after their school enrollment, whereas laterborn children are exposed much earlier, through their older siblings. The authors analyzed sibship size and birth order data from a large case-control study of patients admitted to Athens, Greece, hospitals between April 1976 and October 1984. The analyses included 185 patients with hepatocellular carcinoma, 35 patients with metastatic liver cancer, and 432 other hospital controls. There was a tendency for cases of hepatocellular carcinoma to concentrate at higher birth orders. When the analysis was restricted to cases and controls who were positive for hepatitis B surface antigen, this tendency was even more notable. These results are compatible with the hypothesis that establishment of chronic hepatitis B virus infection at an early age increases the risk of hepatocellular carcinoma substantially more than does chronic infection with this virus established at a later age.

Active and passive smoking and pathological indicators of lung cancer risk in an autopsy study.

OBJECTIVE: The association between involuntary smoking and lung cancer has been supported by most epidemiologic studies, but a number of authors and interest groups claim that the possibility of bias has not been excluded. Few autopsy-based studies have explored the role of active smoking and other exposures in lung carcinogenesis, and none has been previously done to examine the role of passive smoking. We have undertaken such an autopsy-based study in Athens, Greece. DESIGN: Lung specimens were taken at autopsy from 400 persons 35 years of age or older, of both genders, who had died within 4 hours from a cause other than respiratory or cancer in Athens or the surrounding area. For each person at least seven tissue blocks were taken from the main and lobar bronchi and at least five blocks from the parenchyma, including an average of about 20 smaller cartilaginous bronchi and membranous bronchioles. The specimens were examined without knowledge of the exposures of the particular subject in Turin, Italy. For 283 (71%) of the subjects the preservation of the bronchial epithelium was satisfactory for pathological examination, and for 206 among them (73%) an interview could be arranged with their next of kin, focusing on smoking habits of the deceased and their spouses, as well as other variables. The interviewers were not aware of the results of the pathological examinations. MAIN OUTCOME MEASURE: Specimens were examined for basal cell hyperplasia, squamous cell metaplasia, cell atypia, and (in membranous bronchioles and bronchiolo-alveolar airways) mucous cell metaplasia, ie, pathological entities that may be lung cancer risk indicators or epithelial, possibly precancerous, lesions (EPPL). The gland and wall thicknesses were also measured and their ratio calculated (Reid Index). RESULTS: In comparison with nonsmokers, EPPL values were significantly higher among current smokers and higher, but not significantly so, among former smokers. Furthermore, EPPL values were significantly higher among deceased nonsmoking women married to smokers rather than to nonsmokers. In this set of data neither occupation nor residence was associated with EPPL, but this could be due to the poor correlation of residential history with exposure to air pollution and the lack of adequate standardization of contemporary Greek occupations. The Reid Index was higher among smokers and former smokers in comparison with nonsmokers, among subjects with mainly urban residence in comparison with those with mainly rural residence, and among nonsmoking women married to smokers in comparison with those married to nonsmokers, but none of these differences was statistically significant. CONCLUSION: These results provide support to the body of evidence linking passive smoking to lung cancer, even though they are based on a study methodologically different from those that have previously examined this association.

Association between hepatitis C virus and hepatocellular carcinoma using assays based on structural and nonstructural hepatitis C virus peptides.

Stored sera from 181 Greek patients with hepatocellular carcinoma (HCC), 35 patients with metastatic liver cancer, and 416 hospital controls with diagnoses other than malignant neoplasm or liver disease were examined with first and second generation hepatitis C virus (HCV) enzyme immunoassays as well as with five HCV supplemental assays based on structural and nonstructural HCV peptides. Second generation HCV enzyme immunoassays were more sensitive than first generation assays. However, both assays had suboptimal specificity using the standard reactivity criterion (absorbance of sample to cutoff greater than or equal to 1.0). Specificity was improved by centrifugation and by using a sample's optical density to cutoff ratio greater than or equal to 3.0 or supplemental assays; in this instance the prevalence of antibodies to HCV was 13.3% (24 of 181), 0 (0 of 35), and 1.4% (6 of 416) in HCC, metastatic liver cancer, and hospital controls, respectively. A similar estimation of prevalence of antibody to HCV in HCC (12.5% or 4 of 32) was obtained when the recombinant immunoblot assay, second generation, was used to screen a random sample of HCC patients. The relative risk linking HCV to HCC was estimated as 10.4 (95% confidence interval, 4.2-26.0; P less than 0.0001). These data suggest that the prevalence of antibodies to HCV in HCC using stored sera has been previously overestimated even though the evidence of a causal association of HCV with HCC persists.

Liveborn children and risk of hepatocellular carcinoma.

Clinical, animal, and epidemiologic evidence indicates that exogenous steroids influence the risk of hepatocellular carcinoma (HCC) and a recent study suggested that parity also may increase the risk of this tumor in women. The latter hypothesis was evaluated in the data from a case-control study which was carried out in Athens and covered 166 male and 19 female cases of HCC, and 381 male and 51 female hospital controls. Among males, there was no association between the number of liveborn children and risk of HCC, whereas among women, there was a suggestive positive association. Compared with women with one or two children, the relative risk for HCC was 0.6 among nulliparous women, 1.3 among those with three or four children and 1.7 among those with five or more children. The association of parity with risk of HCC was limited to women who were positive for hepatitis-B surface antigen (HBsAg) and was not confounded by hepatitis-C virus infection or tobacco smoking. The small number of HCC cases does not permit firm conclusions. If confirmed, however, these results would provide the foundation for a practical preventive advice that could be given to women who are positive for HBsAg.

Urban living, tobacco smoking, and chronic obstructive pulmonary disease: a study in Athens.

We studied the relation of urban living and tobacco smoking to the development of chronic obstructive pulmonary disease. The study was based on 110 incident cases of chronic obstructive pulmonary disease between 50 and 60 years of age who were permanent residents of Athens and 400 control patients hospitalized for traumatic and orthopedic conditions in the same hospitals at the same time. All subjects were interviewed about their smoking habits, place of birth, history of past residence, and years of schooling. We found that subjects with more education have a reduced risk of developing chronic obstructive pulmonary disease, with 4 additional years of schooling corresponding to a 30% reduction of risk. We also found that those who have lived all their lives in urban areas (mostly in Athens) have a twofold greater risk of chronic obstructive pulmonary disease compared with people who have lived exclusively or partly in rural areas before settling in Athens. Finally, we found that smokers have a 10-fold relative risk of developing chronic obstructive pulmonary disease, and this risk is strongly dependent on the number of cigarettes consumed per day. The findings of the present study suggest that air pollution, or another aspect of the urban environment, can be an important contributor to the development of chronic obstructive pulmonary disease.

Epidemiologic assessment of interactions of hepatitis-C virus with seromarkers of hepatitis-B and -D viruses, cirrhosis and tobacco smoking in hepatocellular carcinoma.

A recently introduced enzyme immunoassay procedure for antibodies against the hepatitis-C virus (HCV) was used to test samples from 185 cases with hepatocellular carcinoma (HCC) and 432 hospital controls. The anti-HCV results were examined in conjunction with previously reported data from this study concerning hepatitis-B virus (HBV) serology, hepatitis-D virus (HDV) antibodies, presence of cirrhosis and tobacco smoking. There was evidence for interaction between HBV and HCV in the causation of HCC: as previously reported, the rate ratio (RR) linking the presence of anti-HCV to HCC among subjects positive for hepatitis-B surface antigen (HBsAg) was substantially higher than the corresponding RR among those negative for this marker; furthermore, among HCC patients positive for HBsAg, a high proportion (33/61) of those who were positive for hepatitis-Be antigen (HBeAg) or its antibody were positive for anti-HCV, whereas among HBsAg-positive controls who were also positive for HBeAg or its antibody, none was positive for anti-HCV (0/18; p less than 10(-4)). The anti-HCV-related RR for HCC was also higher among HCC patients with cirrhosis than among those without evidence of co-existing cirrhosis (RR 11.4 vs. 4.4; p = 0.06). In addition, there was some evidence of interaction between tobacco smoking and HCV in the origin of HCC; after controlling for age, sex and HBsAg status, the RR for subjects positive for anti-HCV was 6.8 among smokers but only 3.2 among non-smokers (p = 0.26). By contrast, there was no suggestion of an interaction between anti-HCV and anti-HDV, in agreement with the presumed minimal role, if any, of HDV in HCC etiology. These results support the notion that HCV is involved in the etiology of HCC by advancing, through a chronic liver disease process, carcinogenesis initiated by other factors.

Hepatitis B and C viruses and their interaction in the origin of hepatocellular carcinoma.

Serum taken from patients in a case-control study in Athens, Greece, was used to examine the interactive roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the origin of hepatocellular carcinoma (HCC). An enzyme immunoassay for anti-HCV was used to test serum taken from 185 cases with HCC, 35 cases with metastatic liver cancer (MLC), and 432 hospital controls. Weakly positive anti-HCV results were more strongly related to MLC than to HCC, implying that these anti-HCV results are false positive. By contrast, strongly positive anti-HCV results were significantly related to HCC (relative risk [RR], 6.3), whereas no significant association was evident for MLC (RR, 0.6). The association of anti-HCV with HCC was substantially higher among subjects whose radioimmunoassay was positive for hepatitis B surface antigen (RR, 20.0) than among those whose radioimmunoassay was negative for this marker (RR, 4.8). These findings indicate that HCV infection has an interactive role in the origin of HCC.

Correlation of early pathological lesions in the bronchial tree with environmental exposures: study objectives and preliminary findings.

Lung specimens were taken at autopsy from 214 subjects aged 35 years and over who had died from nonpulmonary causes in Athens or the surrounding countryside. The samples were coded and examined for entities thought to be linked to environmental exposures, reflecting epithelial, possibly precancerous, lesions, as well as for morphological features, which were summarized using Reid's index. Of the 214 specimens, 142 were suitable for pathological examination. Next-of-kin of 101 of the dead people were identified and asked about the subject's exposure to active smoking, passive smoking, possible occupational hazards, dietary factors and proxy indicators of air pollution (residence). Preliminary analysis, controlling for age and sex, indicates that active smoking is related, although not statistically significantly, to both the Reid index (difference, 0.28, corresponding to a one-tailed p value of 0.07) and epithelial, possibly precancerous lesions (difference, 16.7, corresponding to a one-tailed p value of 0.09). Nonsignificant differences were found in the preliminary analysis of this ongoing study with respect to the other environmental factors examined.

Alpha 1-antitrypsin and survival in hepatocellular carcinoma.

The association between serum levels of alpha 1-antitrypsin (alpha 1 AT) at the time of diagnosis and survival was studied in a group of 78 patients with confirmed hepatocellular carcinoma (HCC). All 78 patients were followed until the time of death, which occurred in all instances from HCC, with a median time of 6 months and a range of 1-117 months. Cox's proportional hazards model was utilised in the analysis controlling for sex, age, HBsAg status and logarithmically transformed values of alpha-fetoprotein (alpha-FP). Older patients and patients positive for HBsAg have suggestively higher fatality rates (0.05 less than P less than 0.10) whereas in these data sex and AFP levels were not important prognostic factors. Increased levels of serum at alpha 1AT at the time of diagnosis of HCC were statistically significantly (P less than 0.05) related with shorter survival, patients with higher serum alpha 1AT by 200 mg 100 ml-1 having an expected survival time shorter by about 25%.

Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma.

Tobacco smoking and alcohol drinking histories were obtained from 194 patients with hepatocellular carcinoma (HCC) and 456 hospital controls, and the results were analysed in conjunction with the results of serological determinations of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) in all subjects, as well as the presence or absence of cirrhosis in HCC patients. The relative risk (RR) of HCC (and 95% confidence interval) among HBsAg-positive subjects was 13.7 (8.0-23.5), whereas the excess risk among antibody-positive subjects was small and statistically non-significant. In the presence of cirrhosis the RR for HBsAg-positive subjects was considerably higher (30.7 vs. 7.1 among HBsAg-positive subjects without cirrhosis) indicating that HBV may affect the development of HCC through at least two different and potentially multiplicative mechanisms (DNA integration and liver regeneration). Moderate ethanol consumption does not affect the risk of HCC, but there is a statistically significant and dose-dependent association between tobacco smoking and HBsAg-negative HCC. In most of the developed countries of Europe and North America, where the prevalence of HBsAg carrier state is very low and tobacco smoking very common, more cases of HCC may be due to tobacco smoking than to HBV, even though the RR for HCC is much higher among HBsAg carriers than among tobacco smokers.