Tatjana Baldovin

Epidemiology of HCV Infection

It is estimated that approximately 130-170 million people worldwide are infected with hepatitis C virus (HCV). According to data from WHO community and blood donor surveys, the African and Eastern Mediterranean countries report the highest prevalence rates (>10%). The rates of infection in the general population and the incidence of newly-acquired cases indicate an appreciable change in the epidemiology of the infection in recent years. Prior to the widespread screening of blood donations, infected blood and blood products represented a common source of infection. On the other hand, the high peak in HCV antibodies among the elderly in Italian epidemiological studies on the population at large reflects a cohort effect due to an epidemic of HCV infection occurring after the Second World War. According to data reported by the CDC Surveillance System, the incidence of acute hepatitis C has declined since the late 1980s. In 2005, as in previous years, the majority of such cases in North America and Northern Europe occurred among young adults and injected drug use was the most common risk factor. Other, less commonly reported modes of HCV acquisition are occupational exposure to blood, high-risk sexual activity, tattooing, body piercing and other forms of skin penetration. Finally, the overall rate of mother-to-child transmission from HCV-infected, HIV-negative mothers has been estimated at around 5% (coinfection with HIV raises this figure to 19.4%). HCV prevention relies on identifying and counseling uninfected persons at risk of contracting hepatitis C.

Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population.

Aim To evaluate the hepatitis B virus (HBV) and the hepatitis C virus (HCV) epidemiology in the general population of Northern Italy, a cohort of 965 subjects, all residents (including 47 immigrants), were anonymously tested for HBV and HCV infections. Material and Methods Serum samples were assayed for anti-HCV and anti-HBV markers by enzyme-linked immunosorbent assay and for HCV-RNA by polymerase chain reaction, and the positive cases were genotyped. HBsAg-positive cases were assayed for HBeAg/anti-HBe, whereas HBsAg negatives were tested for both anti-HBc and anti-HBs. Results The overall prevalence of anti-HCV was 2.6%, with a bimodal distribution characterized by the highest prevalence (12%) in subjects over 75 years old. None of the subjects under 25 years old was anti-HCV positive. Anti-HCV positivity was similar in males and females (2.4% vs. 2.7%). HCV-RNA was positive in 40% of cases and genotype 1 was the most common. The HBsAg prevalence was 1%, with a significant difference according to country of origin (0.8% in Italian subjects vs. 6.4% in immigrants, P=0.01). HBsAg positivity increased significantly with age (R2=0.57, P<0.02). The overall percentages for the prevalence of isolated anti-HBs, anti-HBs+/anti-HBc+, and isolated anti-HBc were 23.8%, 8.4%, and 4.2%, respectively. Conclusions Our study provides a new picture of HCV and HBV epidemiology in Northern Italy, with these features: (1) a cohort effect showing a reduction of HCV infection in the elderly, possible due to age-related mortality; (2) an unchanged overall prevalence of HBV infection, despite continuing immigration of subjects from endemic countries.

Association of Maternal Education, Early Infections, and Antibiotic Use With Celiac Disease: A Population-Based Birth Cohort Study in Northeastern Italy

We conducted a population-based birth cohort study of approximately 203,000 babies born in northeastern Italy (1989-2012) to investigate perinatal variables, early infections leading to hospital admission, and antibiotic use in the first 12 months of life as possible risk factors for celiac disease (CD). Incident CD cases were identified from pathology reports, hospital discharge records, and exemptions from prescription charges for clinical tests. Multivariate Poisson regression models were fitted to estimate incidence rate ratios (IRRs). A total of 1,227 children had CD; CD was histopathologically confirmed in 866 (71%). Female sex, maternal age, and high maternal educational level were found to be significantly associated with CD. Gastrointestinal infections were strongly associated with a subsequent diagnosis of CD (IRR = 2.04, 95% confidence interval (CI): 1.30, 3.22). Antibiotic use was significantly associated with CD onset (IRR = 1.24, 95% CI: 1.07, 1.43), with a dose-response relationship for number of courses (P-trend < 0.01). Cephalosporin use strongly increased the risk of CD (IRR = 1.42, 95% CI: 1.18, 1.73). Use of antibiotics (supported by the dose-response relationship) and gastrointestinal infections in the first year of life may facilitate the early onset of CD by altering intestinal microflora and the gut mucosal barrier. Perinatal factors, including cesarean section, had little influence on the risk of childhood CD.

Intrafamilial transmission of hepatitis C virus infection.

Background: The role of intrafamilial HCV transmission is still controversial. Methods: An overall sample of 2856 consecutive HCV-infected patients was studied. All index cases were interviewed to identify potential risk factors for transmission and underwent the following tests: HBsAg, anti-HBc, HIV, and, qualitative HCV-RNA and genotyping. Results: Coinfection with HBsAg was recorded in 4.7%, and with HIV in 2.6% of the HCV-infected index cases. Anti-HCV was detected in 2.1% of the members of their original families, and in 13.8% of 2662 sexual partners. The overall rate of infection for offspring was 2.3%, but the risk was significantly higher when the index case was female. The risk for sexual partners was significantly higher when the risk factor for the index case was intravenous drug (IVD) use rather than blood transfusion. Logistic regression analysis showed that female gender and drug addiction in sexual partners of index case were independent factors significantly associated with HCV transmission to sexual partners. Conclusions: Among all family members of index cases, sexual partners of IVD users were at greatest risk of HCV infection. Sexual transmission may not be the main route of transmission though, since IVD use in the sexual partners themselves was independently associated with HCV infection.

An update review on risk factors and scales for prediction of deep sternal wound infections

Surgical site infections are the most common nosocomial infections in surgical patients. The preventable and the unmodifiable risk factors for deep sternal wound infections (DSWI) have been amply assessed in the literature. The aim of this review was to describe the results of the numerous published studies to describe all the DSWI risk factors and the scales devised to predict SWI, with a view to providing an update on this issue. A comprehensive search of the Medline and Embase databases was performed (considering studies from January 1995 to April 2011); and a manual search was also conducted using references cited in original publications and relevant review articles. There are several risk factors associated with DSWI, which could be classified in four categories as demographic (e.g. sex and age), behavioural (e.g. smoking and obesity), baseline clinical conditions (e.g. diabetes, hypertension and COPD) and surgical operative risk factors (e.g. duration of operation and emergency operation). Six scales for predicting the risk of DSWI are described in the literature: they vary not only in accuracy but also in ease of application and they are applied at different times (some only preoperatively and others also postoperatively). This study provides a broad update on our knowledge of the risk factors for DSWI and the scales for prediction with a view to improving the management of infections at cardiosurgery units.

Hepatitis A, B, and C Infection in a Community of Sub‐Saharan Immigrants Living in Verona (Italy)

BACKGROUND In Italy, about 5% of the population is represented by immigrants. The epidemiology of hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection in Africa is very different from Europe; the present study aimed to assess the seroprevalence of viral hepatitis infections in sub-Saharan African immigrants living in Verona. METHODS A total of 182 illegal immigrants were interviewed concerning sociodemographic characteristics and epidemiological information. Their serum was tested for anti-HAV [immunoglobulin (Ig) G and IgM], HBV (HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe), and HCV (anti-HCV) markers. RESULTS The immigrants (age: 3 mo-60 y) were mostly single and males, with a higher education; only 50% of them declared having a regular job. Anti-IgG HAV+ prevalence was 99.5% (100% HAV positivity in the younger age bracket). As for HBV, 67.6% (123) of the immigrants were naturally infected and 9.3% had chronic infection; 4.4% were anti-HBs+ isolated (vaccinated). For HBV infection (any HBV marker), a significant difference was only found for increasing age ( p < 0.01) and married people ( p < 0.001). A statistically significant prevalence of HBsAg was found among the unemployed ( p < 0.001) and those with a lower education ( p < 0.05). Five cases (2.7%) resulted in HCV+ with no reported specific risk factors and with no significantly different sociodemographic features; these people tended to report a low level of education and unemployment. CONCLUSIONS HAV and HBV positivity is higher than in the autochthonous population. While HAV positivity merely represents past infection, the high prevalence of HBsAg in immigrants and the presence of HBsAg/HBeAg in the same group may represent a risk for HBV transmission. The HCV positivity rate resulted similar to the prevalence of the Italian population.

Varicella: epidemiological aspects and vaccination coverage in the Veneto Region

BackgroundWith the control of many infections through national vaccination programmes, varicella is currently the most widespread preventable childhood disease in industrialized nations. In 2005 varicella vaccination was added to the Veneto Region routine immunization schedule for all children at 14 months of age and 12 year-old susceptible adolescents through an active and a free of charge offer. To evaluate parameters at the start of the programme, we conducted a study to describe the epidemiology of varicella infection and coverage rates for varicella vaccine in the Veneto Region (North-East Italy).MethodsWe examined incidence rates and median age of case patients in the Veneto Region for 2000-2007 period using two data sources: the mandatory notification of infections diseases and the Italian Paediatric Sentinel Surveillance System of Vaccine Preventable Diseases. Corrected coverage rates were calculated from data supplied by the Public Health and Screening Section of the Regional Department for Prevention.ResultsIn the Veneto Region from 2000 to 2007, a total of 99,351 varicella cases were reported through mandatory notifications, mostly in children under 15 years of age. The overall standardised annual incidence ranged from 2.0 to 3.3 per 1,000 population, with fluctuations from year to year. The analysis by geographic area showed a similar monthly incidence rate in Italy and in the Veneto Region. The vaccination average adherence rate was 8.2% in 2004 cohort, 63.5% in 2005 cohort and 86.5% in 2006 cohort. Corrected coverage rates were 8.1% in 2004 cohort, 59.9% in 2005 cohort and 70.0% in 2006 cohort, respectively.ConclusionData from passive and active surveillance systems confirm that varicella is a common disease which each year affects a large proportion of the population, mainly children. Uptake of the varicella vaccination programme was strikingly good with average coverage rates of about 70% after only 3 years. Sustained implementation of existing vaccine policies is needed to warrant any significant reduction of varicella incidence in the Veneto Region. Continued surveillance will be important to monitor the impact of the recently introduced mass vaccination policy.

Pegylated Interferon Alpha-2b Plus Ribavirin for Naive Patients With HCV-related Cirrhosis

Background Data on the efficacy of antiviral therapy in patients with HCV-related compensated cirrhosis are generally drawn from analyzing subgroups in larger trials. Aims (1) To analyze the safety and efficacy of combination therapy in naive patients with HCV-related cirrhosis; (2) to evaluate the factors influencing the sustained virologic response (SVR) in cirrhotic patients by comparison with a group of noncirrhotic patients; (3) to analyze the outcome of cirrhotic patients either acquiring SVR and nonresponders to the antiviral therapy during the posttreatment follow-up. Methods We consecutively enrolled 365 patients with biopsy-proven HCV-related chronic hepatitis meeting the inclusion criteria for pegylated interferon a-2b plus Ribavirin: 87 patients had compensated liver cirrhosis and 278 had histologic stages between 1 and 4 according to Ishaks classification. Results The 2 groups were comparable for genotype, viral load, and alanine transferase at presentation. Cirrhotic patients were significantly older and had significantly higher body mass index, serum ferritin, and gamma-glutamyl transpeptidase. The rate of side effects was similar in the 2 groups, whereas the rate of SVR was significantly lower in cirrhotic (45.9%) than in noncirrhotic patients (65.8%). Logistic regression analysis showed that genotype 1 to 4 and high viral load were independent variables correlating with nonresponse in the sample as a whole. During follow-up, hepatocellular carcinoma developed in 5/38 (13.2%) cirrhotic patients not responding or relapsing after treatment. No cases of hepatocellular carcinoma were seen among cirrhotic or noncirrhotic patients with a SVR. Conclusions Cirrhotic patients with compensated disease have a reasonably good chance of virologic response and should be offered treatment, carefully monitoring any side-effects.

Response to influenza vaccine in people with non-protective HI antibody titers

The purpose of the study was to determine which factors correlate directly with response to vaccination in such a group of subjects with non-protective HI antibody titers before vaccination. Two vaccines were used, a subunit virus vaccine adjuvanted with MF59 and a split virus vaccine. The analysis indicated that immunization with vaccine adjuvanted with MF59 was an independent variable for immune response against A/H3N2 (OR: 3.51; 95% CI: 1.81–6.79) and B (OR: 2.31; 95% CI: 1.37–3.89). The results suggest that antibody response to vaccine is satisfactory in elderly people previously lacking a protective antibody titer, and that the adjuvanted vaccine reveals a better immunogenicity.

Female patients in fertile age with chronic hepatitis C, easy genotype, and persistently normal transaminases have a 100% chance to reach a sustained virological response

Background Patients with chronic hepatitis C and persistently normal alanine transaminase levels have recently been included in the guidelines for antiviral treatment. Aim To evaluate the efficacy of PEG-interferon &agr;-2a and weight-based ribavirin doses in patients with these characteristics in a single Italian centre. Materials and Methods Patients with chronic hepatitis C and at least three normal alanine transaminase values over a 12-month period were offered a treatment with PEG-interferon &agr;-2a 180 mg/week and ribavirin (800 mg/day for weight <60 kg; 1000 mg/day for weight >60 and <75 kg; 1200 mg/day for weight >75 kg) for 24 weeks (according to genotype 2 or 3) or for 48 weeks (according to genotype 1 or 4). Each patient at baseline underwent liver stiffness (LS) examination using Fibroscan. Data were analysed according to the intention-to-treat criteria. Results A total of 227 patients (55 men, 172 women) were enrolled into the study: 65 (28.6%) had genotype 1, 144 (63.4%) genotype 2, nine (4.0%) genotype 3 and nine (4.0%) genotype 4. Patients with genotype 2 or 3 (N=153 with easy genotypes) were allocated in group 1 and those with genotype 1 or 4 (N=74 with difficult genotypes) in group 2. According to the LS measurement, patients were classified as follows: 159 (70.0%) presented absent or mild fibrosis (LS=2.5–7.0 kPa), 61 (26.9%) patients had significant fibrosis (LS=7.1–9.5) and seven (3.1%) patients had severe fibrosis (LS >9.6). Twelve patients (5.3%) dropped out within 4 months because of side-effects, whereas 215 patients completed the study. Overall, 13 patients were considered nonresponders (5.7%) and six patients (2.6%) were relapsers to the therapy. The sustained virological response (SVR) rate was 85.4% and it was higher in ‘easy’ genotypes (2 or 3) compared with ‘difficult’ genotypes (1 or 4) (92.2 vs. 74.3%, P<0.001). No statistical difference was found in the SVR rate between patients presenting absent or mild fibrosis as against those with significant fibrosis. Multivariate analysis, including factors correlated with SVR, showed that easy genotype and female sex are significantly associated with a SVR. Conclusion Patients with chronic hepatitis C and persistently normal transaminases have an 85.4% chance to clear the virus with conventional antiviral treatment. Female patients in fertile age with easy genotypes have a 100% chance to reach a SVR.