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Background and Aims The natural history of ADPKD has been defined in numerous studies in various countries and in various genetic and environmental contexts but the problem has not yet been studied in sufficiently large studies in the Italian population. We have studied the evolution of ADPKD in a cohort of 445 incident patients enrolled in a time span between 2012 and 2016 in 28 nephrological centers in 3 regions of central Italy. The main demographic and clinical characteristics of this cohort are reported below. [GRAPHICS] Method The analysis was carried out on a sample of 296 patients with at least 2 creatinine measurements prior to ESKD and with eGFR at onset ≥45 ml/min/1.73m2. The median follow-up was 15 years (range 1-42 years). The analysis of the data was carried out with the Joint model, an approach that allows the simultaneous modeling of longitudinal (repeated over time) and time to event ESKD or GFR [GRAPHICS] [GRAPHICS] Results The average eGFR decline in the entire population was -2.13 ml/min/1.73m2/year. In males the decline in GFR was significantly higher than in females (M: -2.63 ml/min/1.73m2; in F -1.74 ml/min/1.73m2/year, p In the longitudinal model the age at diagnosis >30 years and the presence of hypertension were significantly associated with an accelerated decline in GFR and patients older than 50 years exhibited a reduction by 35 ml/min/1.73m2 greater than those younger than 30 years. In the survival model the GFR trend and sex were associated with the risk of renal survival. For each incremental baseline unit of GFR the risk for ESKD decreased by 16% (HR: 0.84) and in females the risk was about one third compared to males (HR: 0.31). Conclusion This study, the first to apply the joint model in the analysis of the evolution of renal function in ADPKD and the first in a sizeable cohort in Italy, provides important information on the progression of polycystic kidney disease in an incident series of Italian patients with ADPKD.

The epidemiological scenarios of hepatitis E virus (HEV) and hepatitis A virus (HAV) infections have changed in the last few decades, but precise epidemiological data on the prevalence of anti-HEV and anti-HAV, alone or in combination, in the general population are scanty. We investigated HEV and HAV seroprevalence comparing two population samples living in Northern (Abbiategrasso, Milan) and Southern Italy (Cittanova, Reggio Calabria), the latter being characterized by a poorer socio-economic level and hygienic/sanitary conditions. Based on census records, we randomly enrolled and tested 3,365 subjects (Abbiategrasso, n = 2,489; Cittanova, n = 876) aged 18-75 years for anti-HAV and anti-HEV. Anti-HAV (71.3 % vs 52.5 %) and anti-HEV (17.8 % vs 9.0 %) prevalence rates were higher in Southern Italy (both p

The prevalence of risk factors for cardiovascular and metabolic diseases was investigated in an adult population of the city of Cittanova, Southern Italy.The study was conducted among 992 randomly selected adults aged 18-75 years, between April 2009 and January 2011.Prevalence rates of non-alcoholic fatty liver disease (NAFLD), overweight, obesity, and metabolic syndrome (MS) were 24.8%, 41.5%, 27.1%, and 34.4%, respectively. For the components of MS, prevalence of central obesity was 47.4%, impaired fasting glucose (IFG) 34.7%; hypertension 53.7%, low high-density lipoprotein (HDL) cholesterol 34.2%, and hypertriglyceridemia 27.2%.Hypertension, central obesity, IFG, low HDL cholesterol, hypertriglyceridemia, MS, and increased carotid artery intima-media thickness (IMT) were significantly associated with NAFLD after adjustment for age and sex. With additional adjustment for body mass index (BMI), IMT and MS (depending on the prevalence ratio that was investigated), the positive association between the NAFLD and increased IMT lost statistical significance, while that with body mass index (BMI) and MS remained significant.

Il rene policistico rappresenta a tutt'oggi la malattia ereditaria più importante per il nefrologo a causa della sua ampia diffusione tra i pazienti con insufficienza renale e tra quelli in trattamento emodialitico. Inoltre, la malattia è gravata da importanti comorbidità che complicano la vita dei pazienti ed è caratterizzata da un invalidante corredo sintomatologico (dolore acuto o cronico, ingombro addominale, disturbi gastrointestinali). Tuttavia è ancora sconosciuta la storia naturale della malattia e questo rende ancora più difficile pianificare e progettare modalità di approccio che possano coinvolgere tutte le strutture sanitarie, sia territoriali che ospedaliere. La possibilità di creare un network attraverso i moderni mezzi informatici e quindi avere in modo semplice ed economico un database in grado di raccogliere numerose informazioni (sia cliniche sia epidemiologiche) sui pazienti affetti potrebbe rappresentare un valido strumento che consentirà di individuare più facilmente i pazienti affetti dalla malattia e di migliorarne la gestione clinica.

Autosomal dominant polycystic kidney disease (APDKD) is the most relevant hereditary disease in Nephrology being commonin patients with renal failure or in hemodialysis. The disease has significant comorbidities complicating the everyday life of patients, and is characterized by a disabling set of symptoms: acute or chronic pain, abdominal obstruction, and gastrointestinal disorders.The natural history of the disease is still unknown, thus making it hard to plan and design the appropriate clinical approaches.A modern information network as well as a web database, aimed at gathering a variety of patient information (clinical and epidemiological), could be a valuable tool to identify more easily patients suffering from the disease and, thus, improve clinical management.

Background Systematic reviews (SR) of clinical evidence are rightfully considered the basis for developing recommendations to support decisions in current practice. To avoid bias, SRs are expected to be systematic in their research strategy and are exhaustive. The drawback of the latter criteria relies in the substantial work needed to conduct and keep SRs updated. The objective of this paper is to compare a research strategy based on the review of a selected number of core journals, which we consider a ‘pragmatic review’ (PR), with that derived by an SR in estimating the efficacy of treatments. Methods Five clinical areas were considered for the comparison between the two strategies: chronic obstructive pulmonary disease, dermatology, heart failure, renal diseases and stroke. We extracted a systematic sample from all the Cochrane SRs pertaining to each area and were published before April 2010. Two groups of journals were considered in the PR: six general journals that commonly published research for the five clinical areas, and five specialist journals with the highest impact factor in each area. To assess the agreement in the findings of SRs and PRs, we considered both the direction of the estimates and P-values. Results A sample of 27 SRs included 171 overall analyses and 259 subgroup analyses related to primary outcomes. The PR captured one or more clinical trials in 24 of the 27 SRs (89%), and 118 of the 171 overall analyses (69%) were replicated. The PR supported the recommendations to use (or not) the study treatment in 11 of the 13 SRs (85%), which ended with a clinical recommendation. Conclusions We verified in a sample of SRs that the conclusion of a research strategy based on a pre-defined set of general and specialist medical journals is able to replicate almost all the clinical recommendations of a formal SR.

Over the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis viruses may contribute to lymphomagenesis, and discuss the therapeutic fallouts from this knowledge. Most of this evidence is on HCV, and this is the main focus of the review. Moreover, we mainly address the association with NHL, the most prevalent hematologic malignancy, and the most extensively investigated with regard to an association with hepatitis viruses. Available evidence on the association with other hematologic malignancies is also addressed briefly.

Obesity and exposure to cardiovascular risk factors during adolescence may be associated with the development of atherosclerosis and cardiovascular diseases later in life. The objective of the study was to investigate whether any excess body weight, including moderate overweight, is associated with a more severe cardiovascular risk profile and signs of early atherosclerosis in a pediatric population.A cross-sectional study was conducted among 646 adolescents ages 11 to 13 years from several primary schools of Reggio Calabria, Italy. Body mass index, waist circumference, blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein (CRP) were determined. All of the subjects underwent carotid ultrasonography for the measurement of intima-media thickness. Complete clinical data were available from 575 subjects.Overweight was similarly frequent in boys and girls (31.2% vs 31.0%), whereas prevalence of obesity was higher in boys (18.4% vs 10.1%). Subjects with lower levels of HDL and higher levels of triglycerides, insulin, and CRP plasma were observed more frequently among overweight and obese subjects than nonoverweight. At multivariate analysis, HDL cholesterol, insulin, and CRP were associated (P0.05) with overweight and obesity in girls, whereas in boys, insulin and CRP were associated (P0.05) with overweight and obesity, and LDL cholesterol with obesity. The association between overweight or obesity and increased intima-media thickness, a sign of early atherosclerosis, was present in girls (P0.05) and was close to statistical significance in obese boys (P = 0.07).Overweight and obese adolescents have a higher prevalence of cardiovascular risk factors and show signs of early atherosclerosis. In girls, in particular, overweight is sufficient to determine a more severe cardiovascular risk profile.

Background Peginterferon plus ribavirin treatment induced a sustained virological response in >50% of HCV-RNA-positive individuals enrolled in published clinical trials. Aim To determine anti-HCV treatment effectiveness at a general population level. Patients and methods In 2002, a 1:5 random sample of >11 years old inhabitants of a small Italian town (Cittanova) was invited for HCV screening. HCV-RNA-positive individuals were evaluated for antiviral treatment. Results 1645 of 1924 invited individuals (85.5%) participated in the screening. 84 HCV-RNA-positive individuals were detected: median age was 65 years (range: 32–87); 67% was infected with genotype 1 or 4. Antiviral treatment was judged unnecessary for 43 (51.2%), due to persistently normal alanine aminotransferases, mild disease at liver biopsy or age >70 years without cirrhosis. Twenty-eight of the remaining 41 patients (68.3%) were ineligible for treatment, because of medical/psychiatric contraindications (42.9%), alcohol/drug abuse (17.9%), decompensated cirrhosis/hepatocellular carcinoma (17.9%), not attending official appointments (10.7%), previous intolerance/non-response to interferon plus ribavirin (10.7%). 5 of 13 eligible patients (38.5%) did not receive treatment (4 refused and 1 accidental death). 3 of 8 treated patients (37.5%) reached a sustained virological response. Conclusions Although efficacy of anti-HCV therapy improved in recent years, we found that low eligibility to treatment still limited its effectiveness at general population level in a highly endemic town.

Aim: The effectiveness of early intervention in schizophrenia is still under discussion. The guidelines described in the present paper were aimed at contributing to the current debate by providing Italian practitioners, families, patients and health managers with evidence-based information on early intervention. They also examined the diagnostic tools that are currently available for assessing different stages of psychotic disorders. Methods: A multidisciplinary panel of experts (the Guidelines Development Group) used a set of key-questions to develop an explicit search strategy to conduct a systematic review of the literature published from January 2000 to June 2006. Trained personnel then selected papers from those yielded by the literature search. The Guidelines Development Group's final recommendations were scaled according to the Italian National Guidelines System grading system. Results: The evidence available up to the time of the literature search does not allow for recommendation of early intervention targeting prodromal or at-risk patients to prevent progression from the prodromal phase to acute, full-blown psychosis, nor to improve prognosis. Conversely, identification and timely treatment of first-episode psychotic patients through specific early intervention programmes are highly recommended. Conclusions: The Italian Guidelines on early intervention in schizophrenia are based on a comprehensive assessment of an updated, large-scale body of literature. They draw specific, evidence-based conclusions to assist clinicians and stakeholders in the planning and implementation of appropriate intervention programmes. Further research is needed to ascertain the effectiveness of early intervention in delaying or preventing the conversion to psychosis and improving prognosis in prodromal or at-risk patients. Further investigation is also required for first-episode and critical period patients.

A persistent increase in non-virus non-alcohol related aminostransferase levels can have multiple causes, which differ in terms of prevalence and clinical importance. In the general population, the most frequent cause is non-alcoholic hepatic steatosis, which can evolve into steato-hepatitis and cirrhosis. The treatment for steatosis and non-alcoholic steato-hepatitis consists of modifying lifestyles, whereas the effectiveness of drug treatment remains to be determined. Other much less frequent (yet not rare) causes of persistent non-virus non-alcohol related elevations in aminotransferase levels are celiac disease and hemochromatosis, whereas autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and alpha-1-anti-trypsin deficit are rare. Given that some of these conditions are susceptible to treatment, early diagnosis is important. No epidemiological data are available for evaluating the prevalence of elevated aminotransferase levels correlated with the toxicity of drugs or other xenobiotics, including herbal products. The present document, created by a panel of experts based on a systematic review of scientific evidence, is mainly geared towards physicians working in General Medicine and Transfusion Centres, who generally represent the first contact of persons with elevated aminotransferase levels. The document includes suggestions for diagnosing causes of persistent non-virus non-alcohol related increases in aminotransferase levels, considering the frequency and response to treatment. The conditions requiring specialized visits are also indicated.

Background/Aims: Several studies suggest that the evolutionary rate of HVR1 sequence in acute HCV hepatitis derives from the action of a continuous immune-driven positive selection. However, these studies have not been performed examining the relationship between HVR1 evolution and the development of specific immunity to autologous HVR1 sequences. Methods:We performed a longitudinal analysis of HVR1 sequences and specific antibodies and CD4+ T cells in ten HCV acutely infected patients with different clinical outcomes (recovery versus persistence). Results: We showed that although both recovered and chronically evolving individuals developed IFN-gamma+ T cells specific for Core and NS sequences, HVR1-specific CD4+ T cells were detected only in patients clearing the virus. On the contrary, all patients displayed anti-HVR1 antibodies that recognized sequences exclusively carried by autologous viruses. Measurements of genetic diversity and the number of non-synonymous per synonymous substitutions within HVR1 sequences before and after antibody appearance showed an increase of these parameters only in concomitance with the appearance of anti-HVR1 antibodies. Conclusions: The evidence that anti-HVR1 antibodies favor HVR1 variant selection suggests that viral complexity in chronically infected patients could represent a virus adaptive strategy to escape the continuous selective process mediated by anti-HVR1 antibodies. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.

In 1992, 620 adolescents were vaccinated against hepatitis B. Anti-HBs concentrations were measured in 480 (77.4%) adolescents 1 month after completion of the primary course of vaccination. To assess the persistence of anti-HBs, 347 and 228 of such vaccinees were retested for anti-HBs in 1999 and for anti-HBs and anti-HBc in 2003. More than 10 years after vaccination, individuals with anti-HBsor=10 mIU/ml were considered protected while those with antibody10 mIU/ml were given a booster dose and retested 2 weeks later. Check performed in 2003 showed that 208/228 (91.2%) vaccinees retained protective concentrations of anti-HBs. All vaccinees were anti-HBc negative. 11 of the 12 (91.7%) individuals who were given a booster dose of vaccine showed a vigorous anamnestic response while the remaining one showed a weak response (10.6 mIU/ml). These data suggests that hepatitis B vaccination can confer long-term immunity and that immunological memory can outlast the loss of antibody. Hence, the use of routine booster doses of vaccine does not appear necessary to maintain long-term protection in successfully vaccinated immunocompetent individuals.

Les historiens de l’antiquité et les archéologues s’intéressent à l’île grecque d’Eubée pour un certain nombre de raisons. Les érudits qui consacrent leurs recherches à l’Italie et à la Sicile sont conscients du rôle appréciable joué par les Eubéens qui, à l’Age du Fer, ont été les premiers à établir des contacts entre la Grèce et l’Orient d’une part, la Sicile et l’Italie d’autre part, et ont de ce fait contribué à la naissance d’une remarquable civilisation en Occident. Les savants qui étudient l’histoire de la Grèce sont conscients du fait que l’Eubée semble avoir été un important centre d’activités au VIIIe siècle avant J. -C., période à partir de laquelle la civilisation grecque a connu un nouvel essor. Le rôle des Eubéens reste cependant à préciser.

Objectives Periodic assessment of surveillance systems is recommended to verify whether they are appropriately monitoring the public health problem under surveillance. The aim of this study was to evaluate timeliness, data quality and representativeness of data reported to the Italian Integrated Epidemiological System for Acute Viral Hepatitis (SEIEVA). Study design Cross-sectional analysis of surveillance data. Methods Quantitative indicators were used to evaluate representativeness of reported cases, data quality, and timeliness between surveillance steps, for reports of acute viral hepatitis cases with date of onset of symptoms from 2009 to 2012 (N = 4516). Results Representativeness was 75%. Over 95% of records reported information on age, sex, city of residence, risk factors for hepatitis A and vaccination status. Information on risk factors for hepatitis B and C were reported less consistently (83%), as was information on early outcome (60%). Wide delays were found between surveillance steps. Conclusions The system collects high quality data on acute viral hepatitis cases in Italy. Timeliness was found to be the main limit and needs to be improved by optimizing web-based reporting procedures, increasing communication with participating centres, improving feedback and increasing dissemination of surveillance results. The study highlights the importance of reporting timeliness to detect outbreaks of acute viral hepatitis.

Background/Aims In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. Methods We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed. Results Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3–29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected. Conclusions HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.

Background and aim. The incidence of hepatocellular carcinoma is high among cirrhotic patients, ranging from 2 to 3% in western cohorts and 6–11% in eastern cohorts. Although only one randomised trial has been performed, clinical practice generally uses periodic screening to detect hepatocellular carcinoma in cirrhotic patients. We reviewed the scientific literature on hepatocellular carcinoma screening. Materials and methods. Evaluation of studies identified through MEDLINE and EMBASE (1990–May 2003). Results. The available screening tests to detect hepatocellular carcinoma are alpha-fetoprotein (cut-off: 20 ng/ml) and ultrasound, which are generally combined. The reported sensitivity and specificity are 50–85% and 70–90%, respectively. An estimated doubling time of about 6 months has led to the use of an interval of 6 months between screenings. Based on the risk of hepatocellular carcinoma, cirrhotic patients are considered as the target population. Screening seems to detect smaller and more frequently unifocal hepatocellular carcinoma; the residual liver function is important for determining the eligibility for effective treatment (resection); hence the prevention is more effective for patients with well-compensated cirrhosis. The survival estimated by non-randomised studies is slightly longer for patients with screening-detected hepatocellular carcinoma, compared to those with clinically detected hepatocellular carcinoma, although few studies have accounted for ‘lead time bias’. Conclusions. Although screening for the early detection of hepatocellular carcinoma has become quite common in clinical practice, its effectiveness remains controversial. Observational studies that have taken into account lead time bias suggest that survival is greater for patients with screening-detected hepatocellular carcinoma, yet the eligibility for effective treatments is low. Considering that only one randomised controlled trial has been conducted, it is crucial to standardise the screening schedule and to evaluate prevention programmes.

Although the secondary transmission of hepatitis A virus (HAV) infection is preventable through vaccination, it is not known whether the vaccination of household contacts is feasible. To this end, we conducted a prospective cohort study among the household contacts, 40 years of age or less, of all persons infected with primary HAV infection (index cases) and admitted to eight hospitals in southern Italy within 7 days of onset. Household contacts were vaccinated, and serum samples were taken at vaccination and after 14 and 45 days. Secondary cases were defined as those with IgM seroconversion occurring at least two weeks after enrolment. Coprimary cases were those assumed to have had the same exposure as the index case. Susceptible cases were those who were negative for both IgG and IgM. A total of 495 household contacts participated (acceptance rate of 65%); 65% were vaccinated within 4 days of admission of the index case and 95% within 7 days. At enrolment, 196 (39.6%) household contacts were immune (IgG-positive serum). During follow-up, 19 (3.8%) were IgM-positive: 13 (2.6%) were coprimary cases and 6 (1.2%; 95% CI: 0.2–3.2) secondary cases (5 identified at 14 days from vaccination and 1 at 45 days). Of the 241 susceptible cases, 192 (79.7%) had developed IgG antibodies at 14 days and only 3 (1.2%) did not develop IgG antibodies at 45 days. The 65% acceptance rate and the finding that 95% of the participating household contacts were vaccinated within 7 days of the index case's hospitalization indicate that timely vaccination is indeed feasible. The necessity of returning for the collection of blood samples probably decreased the acceptance rate.

AIM: To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B. METHODS: Out of 1366 hepatitis B surface antigen (HBsAg) positive subjects consecutively observed in 79 Italian hospitals, 53 (4.3%) showed as the only cofactor hepatitis D virus (HDV) infection [hepatitis B virus (HBV)/HDV group], 130 (9.5%) hepatitis C virus (HCV) (group HBV/HCV), 6 (0.4%) human immunodeficiency virus (HIV) (group HBV/HIV), 138 (10.2%) alcohol abuse (group HBV/alcohol); 109 (8.0%) subjects had at least two cofactors and 924 were in the cofactor-free (CF) group. RESULTS: Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis (P < 0.001), those in group HBV/HDV were younger (P < 0.001), more frequently resided in the south of the country and had cirrhosis (P

The overall situation on viral hepatitis prevention and control in Italy was reviewed and evaluated at a Viral Hepatitis Prevention Board (VHPB) meeting in Catania, Sicily, on 7-8 November 2002. Several specific conclusions, drawn from the presentations and discussions, were considered to constitute an example of how to handle these issues in other European and industrialized countries.

Background. Fulminant hepatic failure is the most serious complication of viral hepatitis. Although this event occurs rarely, it may be fatal. Aims. To evaluate the case fatality rate (several deaths divided by number of cases ×100) for each viral hepatitis type in Italy from 1995 to 2000. Patients. Acute hepatitis cases identified by the surveillance system for acute viral hepatitis, which covers approximately 58% of the Italian population. Results. Twenty-five deaths (0.1%) occurred among the 18 460 acute viral hepatitis cases observed from 1995 to 2000, a rate threefold lower than the 0.3% reported during the period 1985–1994. The highest case fatality rate (0.4%) was seen for acute hepatitis B (18 deaths among 4257 cases). Only one death (0.01%) occurred among the 11 063 acute hepatitis A cases and two deaths (0.1%) among the 1536 acute hepatitis C cases. No deaths were observed among the 309 acute hepatitis A cases superimposed on chronic HBsAg carriers and the 166 superimposed on chronic HCV carriers. Intravenous drug use (22.2% of cases) and other parenteral exposures (22.2% of cases) were the most frequent non-mutually exclusive sources of infection reported by subjects who died of acute hepatitis B. Conclusions. Analysis of surveillance system data from 1995 to 2000 indicates that, in Italy, deaths due to acute viral hepatitis are rare, but most commonly observed with acute hepatitis B. There is no evidence that acute hepatitis A may be fatal in chronic HBsAg or HCV carriers. The overall better survival rate may probably reflect improvements in the treatment of fulminant hepatitis in the last few years in Italy.

summary. Travel to endemic areas is one of the most frequently reported risk factors for infection with the hepatitis A virus (HAV). We evaluated the association between HAV infection and travel, by area of destination. We conducted a case–control study on all cases of HAV infection reported to the Italian National Surveillance System for Acute Viral Hepatitis in the period 1996–2000. The study population consisted of 9695 persons with HAV infection (cases) and 2590 with HBV infection (controls). The risk of acquiring HAV was highest for travel to Asia, Africa and Latin America [Odds Ratio=9.30 (95%CI=6.71–12.9)]; a three-fold statistically significant excess of risk was found for travel to southern Italy (OR=3.03) and to the Mediterranean Area and Eastern Europe (OR=3.15). Travel was implicated in 28% of the cases of HAV infection. When stratifying the analysis by area of residence (northern and central Italy vs southern Italy and the Islands), the above-mentioned risks were confirmed only for those residing in northern and central Italy, with no significant risk for those residing in southern Italy and the Islands. Travel to areas endemic for HAV infection constitutes a considerable risk. Our results highlight the importance of developing health policies for improving environmental and hygienic conditions, as well as the prevention of certain eating habits. Vaccination before travelling to a medium or high endemic area could be a safe and effective means of preventing travel-related HAV infection.

In Italy, a program of vaccination against hepatitis B targeted at the immunisation of persons at high risk began in 1983. In 1991, vaccination became mandatory for all newborns and adolescents. Since then, the vaccine has been given to more than 10 million children, with an outstanding record of safety and efficacy. The coverage rate is globally around 94%, with differences between the Northern and Southern regions, with the latter having the lower acceptance rate. According to the National Surveillance System (SEIEVA), the incidence of acute hepatitis B per 105 inhabitants declined from 5.4 in 1990 to 2 in 2000. The reduction was even greater among 15–24-year-old individuals, where the incidence rate per 105 decreased from 17.3 to 2 in the same period. In parallel with the decline of hepatitis B, hepatitis delta has also declined significantly. Catch-up immunisation of unvaccinated adolescents, as well as an effort to improve the vaccination coverage rate in high-risk groups, are required to ameliorate the efficacy of the vaccination campaign. Routine administration of booster doses of vaccine is not considered necessary to sustain immunity in immunocompetent persons. J. Med. Virol. 67:440–443, 2002. © 2002 Wiley-Liss, Inc.

Background: Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Data on the incidence of HCV in the general population are scarce. Spontaneous viral clearance occurs in 10‐25% of infected individuals after acute infection yet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population. Aims: Anti-HCV prevalence, HCV infection rate, and the kinetics of anti-HCV were studied in a cross section of the general population of central Italy. Study population and methods: Anti-HCV prevalence (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected individuals. Infection rate and antibody kinetics were estimated in 2032 participants for whom a second blood sample was taken after a median follow up of seven years. HCV-RNA determination by polymerase chain reaction was performed on follow up sera. Results: The overall confirmed anti-HCV prevalence was 2.4%. Two participants seroconverted for anti-HCV, giving an overall infection rate of 1.4 cases per 10 000 person years (95% confidence interval 0.2‐5.2 per 10 000 person years). Of the 36 individuals confirmed as anti-HCV positive at enrolment, seven (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with indeterminate results at enrolment were serologically non-reactive at the end of follow up. Of the 25 participants confirmed to be anti-HCV positive at both enrolment and follow up, 23 (92.0%) with stable serological profiles tested positive for HCV-RNA at the end of follow up. Conclusions: There is still a permanent risk, although low, of HCV spread in the general population in an area of low level endemicity. In this setting, a wide spectrum of modifications of viral and antibody patterns can be observed in HCV infected patients.

We conducted a retrospective cohort study to estimate the incidence of major blood-borne agents among Italian blood donors and calculated the risk of infection among blood recipients using the 'incidence/window period model'. The study was conducted among 46 180 blood donors enrolled in six blood centres between 1994 and 1999. During follow-up, seven new infections were confirmed: three donors seroconverted for anti-human immunodeficiency virus (HIV); two for anti-hepatitis C virus (HCV); and two showed hepatitis B surface antigen (HBsAg) reactivity; no cases of syphilis were observed. The incidence rates per 100 000 person/years were: 4.06 (95% CI: 0.82-11.85) for HIV; 2.41 (95% CI: 0.29-8.70) for HCV; and 2.70 (95% CI: 0.32-9.77) for HBsAg; the incidence for total hepatitis B virus (HBV) infection was 9.77 per 100 000 person/years (95% CI: 1.16-35.36). The estimated risk of an infectious blood unit not being detected was: 2.45 (95% CI: 0.13-12.33) per 1 million units for HIV; 4.35 (95% CI: 0.30-22.39) for HCV; and 15.78 (95% CI: 1.16-84.23) for HBV. Overall, an estimated 22.58 per 1 million units are infected. In Italy, the risk of transfusion-transmitted infections is low and is similar to that in other western countries. The introduction of new more sensitive screening tests could reduce the residual risk of transfusion-transmitted infection by 40-80%.

The aim of this study is to determine the 99th upper-reference limit (URL) for cardiac troponin T (cTnT) in Italian apparently healthy subjects.The reference population was selected from 5 cities: Bolzano (n=290), Milano (CAMELIA-Study, n=287), Montignoso (MEHLP-Study, n=306), Pisa (n=182), and Reggio Calabria (MAREA-Study, n=535). Subjects having cardiac/systemic acute/chronic diseases were excluded. Participants to MEHLP project underwent cardiac imaging investigation. High-sensitive cTnT was measured with Cobas-e411 (Roche Diagnostics).We enrolled 1600 healthy subjects [54.6% males; age range 10-90years; mean (SD): 36.4 (21.2) years], including 34.6% aged20years, 54.5% between 20 and 64years, and 10.9% over 65years. In the youngest the 99th URL was 10.9ng/L in males and 6.8ng/L in females; in adults 23.2ng/L and 10.2ng/L; and in elderly 36.8ng/L and 28.6ng/L. After the exclusion of outliers the 99th URL values were significantly decreased (P0.05) in particular those of the oldest (13.8ng/L and 14ng/L). MEHLP participants were divided in healthy and asymptomatic, according to known cardiovascular risk factors (HDL, LDL, glucose, C-reactive protein): the 99th URL of cTnT values of these subgroups was significantly different (19.5 vs. 22.7, P0.05).99th URL of cTnT values was strongly affected by age, gender, selection of subjects and the statistical evaluation of outliers.

A Consensus Conference on Specific Learning Disorders has been promoted by the Italian National Institute of Health (Istituto Superiore di Sanità, ISS). The Consensus Conference consisted in a systematic review of the international literature addressing the issues of diagnosis, risk factors and prognosis, treatment, service delivery and organizational models for Specific Learning Disorders (reading, spelling/writing, calculation). Selected papers were examined by a group of Evaluators and then discussed by a Scientific and Technical Committee, whose conclusions were examined and approved by a Jury Panel. The part on diagnostic issues is presented here, encompassing a systematic discussion of the use and appropriateness of diagnostic criteria, parameters, tasks and psychometric indexes as illustrated in the literature, and providing recommendations for clinical practice. Special attention has been devoted to the collection, analysis and discussion of published data concerning languages with transparent orthography. Controversial issues such as discrepancy criteria, role of reading comprehension and importance of accuracy and fluency are discussed.

Background. In 1991, compulsory hepatitis B virus vaccination and screening for anti-hepatitis C virus of blood banks were introduced in Italy. Aim. To evaluate the impact of preventive measures on the incidence and risk factors for parenterally transmitted viral hepatitis. Methods. Data from the surveillance system for acute viral hepatitis for the period 1985–1999 were used. Temporal trends in distribution of reported risk factors were analysed by comparing three-year periods: 1987–1989 and 1997–1999. Results. The incidence fno. cases per 100, 000 population) of hepatitis B was 12 in 1985 and 3 in 1999; the incidence of hepatitis nonA, non-B decreased from 5 to 1 in the same period. These decreases were more evident among young adults and before rather than after 1991. Multiple sexual partners, other parenteral exposures and dental treatment remain the most common risk factors for parenterally transmitted viral hepatitis. An increase in frequency over time was observed for other parenteral exposures, whereas a marked decrease was evident for blood transfusion and household contact with an HB-sAg carrier. Invasive medical procedures continue to represent an important source of infection. Intravenous drug use was reported particularly by young adults with non A, non-B hepatitis, with increased frequency over time. Conclusions. Non-immunologic measures for preventing hepatitis B and non A, non B due to iatrogenic and other parenteral exposures, combined with hepatitis B virus vaccination, could further reduce parenteral transmission.

This study examined 522 children born to hepatitis B surface antigen (HBsAg)-positive mothers from 1985 through 1994 and evaluated the protection provided by anti-hepatitis B virus (HBV) immunization at birth. Babies were given hepatitis B immunoglobulin and hepatitis B vaccine at birth. At 5-14 years after immunization, 17 children (3.3%) were anti-HB core antigen positive, and 3 also were HBsAg positive. One carrier child had a double mutation, with substitution of proline-->serine at codons 120 (P120S) and 127 (P127S) within the a determinant of HBsAg. Of the 522 children, 400 (79.2%) of 505 still had protective anti-HBsAg titers > or =10 mIU/mL. Thus, HBV vaccination of children born to HBsAg-positive mothers is effective and confers long-term immunity. There is no evidence that the emergence of HBV escape mutants secondary to the immune pressure against wild-type HBV is of concern.

Background/Aims : To evaluate the strength of association between parenterally transmitted viral hepatitis and specific types of invasive procedures. Methods : Data from the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1994–1999 were used. The association of acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023 hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple logistic regression analysis. Results : Most procedures resulted in being associated with the risk of acquiring acute HBV or HCV. The strongest associations were: for HBV infection, abdominal surgery (adjusted OR=3.9; 95% confidence intervals (CI)=2.0–7.5), oral surgery (OR=2.7; 95% CI=1.6–4.5) and gynaecological surgery (OR=2.6; 95% CI=1.2–5.5); for HCV infection, obstetric/gynaecological interventions (OR=12.1; 95% CI=5.6–26.3), abdominal surgery (OR=7.0; 95% CI=3.2–14.9) and ophthalmological surgery (OR=5.2; 95% CI=1.1–23.2). Biopsy and/or endoscopy were associated with HCV, but not with HBV infection. Conclusions : Invasive procedures represent an important mode of HBV and HCV transmission. Since a large proportion of the adult general population is exposed to these procedures and an effective HCV vaccine is not yet available, non-immunological means of controlling iatrogenic modes of transmission are extremely important.

Background/Aim: The aim of the study was to estimate the prevalence, risk factors and genotype distribution of hepatitis C virus (HCV) in the general population older than 5 years of age in a southern Italian town. The positive predictive value of alanine transaminase (ALT) screening in identifying HCV positive subjects was also assessed. Methods: Cluster random sampling from the census of the general population was used. ELISA and RIBA tests assessed the presence of anti-HCV; nested reverse transcription polymerase chain reaction (RT-PCR) was used to identify HCV-RNA; genotyping was performed by INNO-LIPA III. The association linking anti-HCV seropositivity with potential risk factors was assessed by multiple logistic regression analysis. Results: Among the 488 subjects enrolled, 79 (16.2%) were anti-HCV positive. The prevalence increased from 1.2% in subjects 6–29 years of age to 42.1% in those ≥60 years. Forty percent of these positive subjects also had abnormal ALT level and 54.4% were HCV RNA positive by PCR. The positive predictive value of the ALT test in identifying anti-HCV positive subjects was 65%; however, it was 46.7% in subjects younger than 60 years of age and 90.5% in those 60 or older. Genotype 1b was detected in 74% of subjects, type 2c in 23.3%, and type 1a in 2.3%. The only two variables significantly associated with HCV seropositivity in multivariate analysis were age older than 45 years (O.R. 8.5; CI 95%=3.0–24.1) and past use of glass syringes (O.R. 3.4; CI 95%=1.5–7.6). Conclusions: These findings confirm that HCV infection is endemic in southern Italy, particularly among the elderly. Percutaneous exposure, such as injections with nondisposable, multiple-use, glass syringes used in the past for medical purposes may have played a major role in the spread of HCV infection. ALT screening is not useful in detecting HCV positive subjects in the general population, particularly among subjects who could benefit from antiviral therapy.

Using data from the surveillance system for type-specific acute viral hepatitis, the temporal incidence trend of non-A, non-B acute hepatitis and risk factors for acute hepatitis C have been evaluated in Italy. The association between hepatitis C and the potential risk factors (odds ratios, OR) was estimated using hepatitis A patients as controls. The independent roles of the different risk factors were estimated by multiple logistic regression analysis. The incidence of non-A, non-B acute hepatitis declined from 5 per 100 000 to 1 per 100 000 between 1985 and 1996. Anti-HCV data collected by SEIEVA since 1991 showed that 60% of patients with non-A, non-B acute hepatitis were positive for antibodies to the hepatitis C virus (anti-HCV) at the time of hospitalization. During the 6 months prior to the disease onset, the most frequently reported risk factors were multiple sexual partners, other parenteral exposure and intravenous drug use; transmission by blood transfusion declined from 20% in 1985 to 2% in 1996. On multivariate analysis, intravenous drug use (OR=35.5; 95% CI=23.1-54.4), surgical intervention (OR=4.6; 95% CI=3.3-6.5), dental treatment (OR=1.5; 95% CI=1.1-1.9) and two or more sexual partners (OR=2.2; 95% CI=1.6-3.0) were all independent predictors of hepatitis C. These findings indicate that HCV infection is decreasing in Italy. Intravenous drug use, multiple sexual partners, surgical intervention and dental therapy are the main modes of transmission.

L. CROCI, M. CICCOZZI, D. DE MEDICI, S. DI PASQUALE, A. FIORE, A. MELE and L. TOTI.1999.Hepatitis A is a widespread infectious disease world-wide. In Italy, shellfish consumption was shown to be a major risk factor for hepatitis A infection, especially when these products are eaten raw or slightly cooked. The aim of the present study was to evaluate Hepatitis A virus (HAV) resistance in experimentally contaminated mussels treated at different temperatures (60, 80 and 100 °C) for various times. The presence of HAV was evaluated by cell culture infection and reverse transcriptase-polymerase chain reaction confirmation. The experiments, carried out on HAV suspension and contaminated mussel homogenate both containing about 105 50% tissue culture infectious dose ml−1, showed that, under our experimental conditions, the treatments at 60 °C for 30 min, 80 °C for 10 min and an immersion at 100 °C for 1 min were not sufficient to inactivate all the viruses; it was necessary to prolong the treatment at 100 °C for 2 min to completely inactivate the virus. Thus it is advisable to eat only cooked shellfish, paying particular attention to the times and temperatures used in the cooking process, since evidence suggests that the shellfish body may protect the virus from the heat effect.

Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre-pre-B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL. The leukaemogenic activity of the cytotoxic drugs employed for the treatment of PM may have played a potential role in only a proportion of patients, opening the possibility that some sALL patients may have developed two or more malignancies due to individual predisposing factors.

In 1997, prevalence of and risk factors for hepatitis A virus (HAV) infection were evaluated in 146 homosexual and 286 heterosexual men attending a Sexually Transmitted Disease (STD) Clinic in Rome, Italy. Total HAV antibody (anti-HAV) was detected in 60·3% of homosexuals and 62·2% of heterosexuals. After adjustment for the confounding effects of age, years of schooling, number of sexual partners, use of condoms, and history of STD, homosexuals were not found to be at increased risk of previous HAV exposure than heterosexuals (OR 1·1; 95% CI 0·7–1·9). Independent predictors of the likelihood of anti-HAV seropositivity among homosexuals and heterosexuals were: age older than 35 years and positive syphilis serology which is likely a proxy of lifestyles that increase the risk of faecal–oral infections.These findings do not support a higher risk in homosexual men but could suggest a role for the vaccination of susceptible patients attending STD clinics.

The relationships between acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and refractory anaemia with excess of blasts (RAEB) and human herpes virus (HHV)-6 antibody level were investigated in a multicentre case-control study. An association between increased HHV-6 seropositivity and geometric mean titre ratio with AML was shown: P for trend = 0.022, adjusted odds ratio 1.20, 95% confidence interval 1.07–1.33 respectively. No association was found between HHV-6 and ALL, CML or RAEB. © 1999 Cancer Research Campaign

To assess the relative importance of ulcerative and non-ulcerative sexually transmitted disease in the transmission of HIV, a seroprevalence study was conducted on 2210 patients at the sexually transmitted diseases (STD) clinic of the S. Maria e S. Gallicano Hospital in Rome, between 1989 and 1994. Among male patients, by univariate analysis, strong predictors of HIV infection were homosexuality, sexual exposure to a HIV-positive partner, hepatitis B virus infection, and positive syphilis serology. An increased risk was estimated for patients with past genital herpes (odds ratio (OR) 3·86, 95% confidence intervals (CI) 0·40–18·2), and primary syphilis (OR 5·79, 95% CI 0·59–28·6). By multivariate analysis, a positive association was found with homosexuality (OR 6·9, 95% CI 2·9–16·5), and positive syphilis serology (OR 3·5, 95% CI 1·3–9·2). An adjusted OR of 2·41 was calculated for current and/or past genital herpes. These results, although not conclusive, suggest a role of ulcerative diseases as risk factors for prevalent HIV infection, and indicate that positive syphilis serology is an unbiased criterion for identifying individuals at increased risk of HIV infection.

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs. The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died. The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.

Background/Aims: This study aimed to evaluate the incidence of and risk factors for acute viral hepatitis A (HAV) in Italy. Methods: Data were from a surveillance system for type-specific acute viral hepatitis (SEIEVA). To estimate the association of hepatitis A cases with the potential risk factors (Odds Ratios) and the proportion of all hepatitis A cases attributable to a given risk factor (population attributable risk), hepatitis B cases were used as controls. Independent predictors of HAV were estimated by conditional multiple logistic regression. Results: During the period 1985–1994, 25 553 viral hepatitis cases were reported. Of these, 6408 (25%) were due to hepatitis A (HAV). HAV incidence declined from 10/100 000 in 1985 to 2/100 000 in 1987. Since 1991, however, an increase in HAV has been observed. The majority of cases were 15–24 years old; the incidence was higher in males and in subjects residing in southern Italy. Only one death (0.02%) was observed. Shellfish consumption was the most frequently reported risk factor (62%). The proportion of cases reporting personal contact with an icteric case, travel to a high-medium endemic areas, and family contact with a child attending a day-care centre (household of day-care child) was 17%, 19% and 15%, respectively. The results of multivariate analysis showed that shellfish consumption (OR=2.6; 95% CI=2.4–2.9), travel to endemic areas for people residing in northern and central Italy (OR=5.4; 95% CI=4.6–6.2) and household of day-care child (OR=1.2; 95% CI=1.03–1.4), were all types of exposure independently associated with HAV. The estimates of population-attributable risk show that shellfish consumption explained as many as 42.2%, travel to high-medium endemic areas for people residing in northern and central Italy 24.2%, and household of day-care child only 1.4% of all acute hepatitis A cases in Italy. Conclusions: These findings indicate that HAV in Italy is mainly a food-borne disease. Vaccination against hepatitis A is strongly recommended for travellers to endemic areas.

A single-nucleotide polymorphism (SNP; rs12979860) near the IL28B gene has been associated with spontaneous and treatment-induced hepatitis C virus clearance. We investigated predictors of spontaneous disease resolution in a cohort of patients with acute hepatitis C (AHC), analyzing epidemiological, clinical and virological parameters together with IL28B.rs12979860 genotypes and cell-mediated immunity (CMI). Fifty-six symptomatic AHC patients were enrolled and followed prospectively. CMI was measured in 31 patients at multiple time points by interferon-γ enzyme-linked immunospot assay and was correlated to the IL28B.rs12979860 SNP. Eighteen patients had a self-limiting AHC that was associated with female sex (P = .028), older age (P = .018), alanine aminotransferase level1000 U/L (P = .027), total bilirubin level7 mg/dL (P = .036), and IL28B.rs12979860 genotype CC (P = .030). In multivariate analysis, only CC genotype was independently associated with self-limiting AHC (odds ratio, 5.3; 95% confidence interval, 1.1-26.5). Patients with the CC genotype with self-limiting AHC had a stronger (P = .02) and broader (P = .013) CMI than patients with the CT genotype with chronically evolving AHC. In patients with chronically evolving disease, CC genotype was associated with a broader CMI compared to CT genotype (P = .028). A negative CMI was more frequently associated with CT genotype among persistently infected patients (P = .043) and with persistent infection among CT patients (P = .033).. Self-limiting AHC was independently associated with CC genotype. The correlation between IL28B.rs12979860 genotypes and CMI is suggestive of a possible important role of CMI in favoring hepatitis C virus clearance in CC patients.