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Background: Limited data are available on entecavir in Caucasian patients with HBV cirrhosis or chronic hepatitis B who are treated in the clinical practice. The aim was to evaluate the efficacy of entecavir in an Italian cohort of unselected patients with different stages of liver fibrosis, comparing the virological and clinical results obtained between patients with and without liver cirrhosis., Methods: Efficacy and safety of entecavir were retrospectively evaluated in 100 patients recruited in the Gastro-Hepatology Unit, San Giovanni Battista Hospital (Turin, Italy). A pharmacokinetic analysis was performed in 34 participants to assess whether cirrhosis may affect entecavir metabolism. Participants were followed-up for a median (range) duration of 21 months (2-108)., Results: Rates of virological response (negative viraemia by PCR for ≥ 2 consecutive determinations) after 12, 24 and 36 months were 91.7%, 97.5% and 93.7%, respectively. In the 84 patients who were treated for ≥ 12 months, presence of cirrhosis (OR 1.730, 95% CI 1.082, 2.766; P=0.022) and absence of hepatitis B e antigen (OR 0.479, 95% CI 0.273, 0.842; P=0.011) were independent predictors of earlier clearance of serum HBV DNA. There were no differences between the serum concentrations in the steady-state level of entecavir between patients with or without cirrhosis. No significant differences were detected between the average area under the curve in the means of the two groups (P=0.55)., Conclusions: Entecavir represents an excellent therapy in patients with HBV-related liver disease and particularly with cirrhosis where it showed a good profile of tolerability, higher efficacy and an earlier virological response.

Background and Aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non-alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown., Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end-stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism-based assay., Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over-represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06-2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/(*) carriers), to 97/295 (32.9%; male C/(*) carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001)., Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis., (© 2011 John Wiley & Sons A/S.)

Background and Aim: Carriage of the apolipoprotein E (Apo E) variants, E2, E3 and E4, affects cholesterol metabolism and may be involved in the persistence of hepatitis C virus (HCV) infection. Our aim was to verify whether carriage of specific Apo E variants modulates the course of hepatitis C., Methods: We studied a cohort of 116 HCV-positive patients (49 male subjects) with persistently normal transaminases and an Ishak staging score ≤ 2 at an initial biopsy. These untreated patients underwent regular clinical monitoring (median histological follow up: 10 years). Apo E variants were genotyped and results were related to the histological outcome., Results: The mean ± standard deviation staging scores were 0.9 ± 0.7 at entry versus 1.9 ± 1.2 at the end of follow up, P < 0.0001. Initial and final staging scores in the E3/E3 homozygotes (n = 74) were 1.0 ± 0.7 versus 2.1 ± 1.3, P < 0.0001, while in the remaining patients (n = 42) they were 0.9 ± 0.6 versus 1.5 ± 1.0, P < 0.002. A synergistic effect was observed between Apo E polymorphisms and baseline serum cholesterol values: patients not carrying any E3 allele, as well as carriers of a single E3 allele with serum cholesterol concentration > 190 mg/dL were more likely to have a favorable outcome (final vs initial staging score increased in 7/66, did not change in 10/46, and decreased in 3/4, P <0.005)., Conclusions: Some of the variability in the natural history of patients with persistently normal transaminases with initially mild hepatitis C can be related to their Apo E genetic background., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Objective: This was a nationwide prospective study carried out in Italy between 2005 and 2007, involving 34 centers with a neonatal intensive care unit. The study reports the Italian Neonatal Study charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, comparing them with previous Italian data and with the most recent data from European countries., Patients and Methods: Single live born babies with ultrasound assessment of gestational age within the first trimester, and with both parents of Italian origin. Only fetal hydrops and major congenital anomalies diagnosed at birth were excluded. The reference set consists of 22,087 girls and 23,375 boys., Results: At each gestational age, boys are heavier than girls by about 4%. Later-born neonates are heavier than firstborn neonates by about 3%. The effects of sex and birth order on length and head circumference are milder. No differences were observed between babies born in central-north Italy and southern Italy. A large variability emerged among European neonatal charts, resulting in huge differences in the percentage of Italian Neonatal Study neonates below the 10th centile, which is traditionally used to define small-for-gestational-age babies. In the last 2 decades prominent changes in the distribution of birth weight emerged in Italy and in the rest of Europe, in both term and preterm neonates., Conclusions: The existing European neonatal charts, based on more or less recent data, were found to be inappropriate for Italy. Until an international standard is developed, the use of national updated reference charts is recommended.

Interleukin-1 beta (IL-1 beta) genetic polymorphisms and IL-1 receptor antagonist (IL1RN) variable number tandem repeat (VNTR) seem to be related with the occurrence of chronic diseases. This study aimed to verify whether IL-1 beta -511>C/T, -31>T/C, +3953>C/T and IL1RN VNTR were associated to the development of liver cirrhosis. Two hundred forty cirrhotic patients were involved in the study. A significant trend was detected, for increasing cirrhosis frequencies, grouping the patients as follows: females and males carrying neither the IL-1 beta (-511 -31) T-C/T-C or T-C/(T-T or C-C) diplotypes nor any IL1RN A2 allele (138/292), males carrying either the IL-1 beta T-C/T-C or T-C/(T-T or C-C) diplotypes or at least one IL1RN A2 allele (74/147) and males carrying either the IL-1 beta T-C/T-C or T-C/(T-T or C-C) diplotypes and at least one IL1RN A2 allele (28/37) (p < 0.01). IL-1 beta polymorphisms are associated with the occurrence of end stage liver disease. IL-1 beta inflammatory activity appears more pronounced in males.

Preterm Infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth,specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally, the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.

Liver transplantation (LT) recipients are at risk for early and delayed adrenal insufficiency for multiple reasons. Although early adrenal insufficiency is known to occur in a high proportion of recipients maintained on steroid-free immunosuppressive regimens, the prevalence and risk factors associated with delayed functional adrenal gland atrophy (FAGA) are unknown because routine evaluation for this condition is not standard practice among LT centers. We investigated a group of 87 patients (64 males) transplanted for end-stage liver disease related to different etiologies. All underwent a standard corticotropin stimulation test (CST) when, after gradual steroid tapering, they had been maintained for at least 1 week on oral prednisone at a daily dose of 5 mg. FAGA, defined by a serum cortisol concentration that, 60 minutes after corticotropin administration, did not double the baseline level and remained <20 mug/dL, was diagnosed in 23/87 patients (26.4%). Stepwise logistic regression analysis selected as significant predictors of FAGA the cumulative dosage of corticosteroids administered (P < 0.01), the increase in the body mass index after LT (P < 0.01), a low serum cholesterol concentration (P = 0.005), and a high adrenocorticotropin hormone (ACTH) serum level (P < 0.05) at the time CST was performed. In conclusion, FAGA is a common condition among LT recipients who are maintained on prolonged corticosteroid immunosuppressive treatment. Factors associated with FAGA include the cumulative steroid dose, weight changes after LT, and ACTH and cholesterol levels at the time of steroid withdrawal.

Successful therapy in cow's milk protein allergy rests on completely eliminating cow's milk proteins from the child's diet: it is thus necessary to provide a replacement food. This prospective study investigated tolerance of donkey's milk in a population of 46 selected children with cow's milk protein allergy, for whom it was not possible to use any cow's milk substitute. Thirty-eight children (82.6%) liked and tolerated donkey's milk at the challenge and for the entire duration of follow-up. Catch-up growth was observed in all subjects with growth deficit during cow's milk proteins challenge. The degree of cross-reactivity of immunoglobulin E (IgE) with donkey's milk proteins was very weak and aspecific. Donkey's milk was found to be a valid alternative to both IgE-mediated and non-IgE-mediated cow's milk proteins allergy, including in terms of palatability and weight-height gain.

Background: Care procedures for preventing neonatal diseases are carried out according to nurseries' traditions and may be not consistent with the evidence based medicine issues., Methods: A multi-centric survey was conducted in 2 Regions located in NW Italy (Piedmont and Aosta Valley) in order to collect information on some healthy newborn care procedures. During 2001, a questionnaire was sent to the chief pediatrician in charge to the all 33 nurseries of the region asking the methods used during 2000 as prevention of ophthalmia neonatorum, early and late hemorrhagic disease of newborn, umbilical cord care and recommendations of vitamin D administration. Thereafter, during 2004 the same questionnaire was sent to the 34 chief pediatrician of nurseries to evaluate if the procedures were changed during 2003 according to guidelines. The nurseries care for 32,516 newborns in 2000 and 37,414 in 2003., Results: Aminoglycoside eyes drops as prevention of ophthalmia neonatorum were the first choice in both periods (23 out 33 nurseries in 2000 and 24 out 34 in 2003 p > 0.05; the corresponding figures for newborns were 18,984 out 32,516 newborns vs. 28,180 out of 37,414 p < 0.05). The umbilical cord care was carried out with alcohol in 12/33 centers (13,248 newborns) and dry gauze in 3/33 centers (2,130 newborns) in 2000, the corresponding figures in 2003 were 6/34 centers (p > 0.05), (6,380 newborns, p < 0.05) and 12/34 centers (p < 0.05), (18,123 newborns, p < 0.05). The percentage of newborns receiving of i.m. vitamin K. at birth increased during the study period (15,923/32,104 in 2000 vs. 19,684/37,414 in 2003, p < 0.01), but not the number of nurseries (16 in 2000 and 17 in 2003 p > 0.05). The numbers of parents of newborns who receive the recommendations of oral vitamin K during the first months life decreased from 2000 (25,516/30,606) to 2003 (29,808/37,414, p < 0.01) as well as for Vitamin D recommendation (14,582/30,616 in 2000 vs. 11,051/37,414 in 2003, p < 0.01). Oral vitamin K during the first months of life was recommended by 25 nurseries in 2000 and 27 in 2003 (p > 0.05), the corresponding figures for Vitamin D were 15 and 14 (p > 0.05)., Conclusion: In the present study a large variability of procedures among the nurseries was observed. During the study periods, guidelines and evidence based medicine issues have only partially modified the neonatal care procedures In Piedmont and Aosta Valley nurseries. These observations suggest to implement local forum/consensus conference to standardized procedures as much as possible.

Fifty-one consecutive isolates of Mycobacterium tuberculosis, collected during a 2-year period in the north-east of Italy, were subjected to IS6110-RFLP analysis to detect the presence of clusters and assigned to one of the three genotypic groups delineated by single nucleotide polymorphisms in the genes katG and gyrA. All the isolates collected from the local population belonged to group 2 or 3, while group 1 isolates were found only in specimens collected from African immigrants. Clustered cases of tuberculosis, which are likely to be related to recently transmitted infection, were found to be significantly associated with katG gyrA group 2. In the local situation, strains belonging to this group may therefore present a higher risk of transmission.

Toxo-net is a regional program of survey on congenital toxoplasmosis which has two aims: 1) to estimate the incidence of gestational and congenital toxoplasmosis in our Region (Piemonte); 2) to assess the compliance to our diagnostic, therapeutic and follow-up protocols which are thoroughly described. Thirty-two obstetrical, neonatal and laboratory units of Piemonte Region have been involved. During 18 months (January 1997-June 1998) 365 pregnant women were studied because of suspected seroconversion: in 129 patients infection was confirmed. Amniocentesis for prenatal diagnosis was carried on 11 patients; two fetuses were affected. 35% of the mothers were untreated or inadequately treated. Hydrocephaly was observed in two fetuses. Neonatal follow-up at 12 months is available for 68 of the 129 infected mothers. Four babies (5.8%) were infected, three of them being symptomatic; their mothers had not been treated. It is concluded that the implementation of a screening program for toxoplasmosis during pregnancy seems to be beneficial. However an effort to improve the surveillance system and the education of the gynecologists, general practitioners and of the patients is needed, and economic evaluations are warranted.

Aim of this study is to compare traditional post-partum hospital stay to hospitalization associated with early protected discharge: a case-control study has been performed to evaluate outcome as mother's appreciation of the experience as well as breastfeeding. The study included 50 healthy-term newborns and their mothers, discharged within 24 and 48 hours of life, and 44 controls, who had traditional "rooming-in" stay, delivered at the Department of Neonatology--University of Turin. The protocol included a midwife daily home visits and a neonatologist and nurse visit within 4th to 5th day of life, to evaluate mother's and baby's health status and to perform metabolic screenings. An ambulatorial follow-up visit at 1 month of life and 2 telephone interviews, at 3rd and 6th month, were also planned. During the first week of life 45 (90%) early discharged newborns had complete nursing (breastfeeding + water or other fluids), 4 (8%) had complementary nursing (breastfeeding + formula) and 1 (2%) received formula. Among controls, 46 (92%) babies received complete nursing, 2 had complementary nursing and 2 had artificial nursing. At 6 months of life breastfeeding was complete for 2% of cases and 6% of controls; in 44% of cases and 56% of controls nursing was complementary. Readmissions to our Birth Center were 2 among early discharged newborns, 1 in the control group. About project's appreciation, 96% of early discharged and 98% of control group mothers declared their availability to repeat the experience. Caring and supporting were judged adequate in 94% of both group. By adequate supporting of mother and newborn, short and traditional hospitalization are both pleasant and don't seem to present significant differences in type and length of nursing.

We compared the results of genotyping hepatitis C virus (HCV) either by PCR amplification of the core region or by hybridization of PCR-amplified products of the 5' untranslated region (5'UTR assay). Serum samples from 144 Italian anti-HCV-positive patients (106 drug abusers and 38 patients with chronic viral liver disease but no history of drug abuse) were studied. The original core region assay described by Okamoto et al. (H. Y. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyakawa, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) allowed genotyping of 75 of 144 samples. A modified version of Widell et al. (A. Widell, S. Shev, S. Månsson, Y.-Y. Zhang, U. Foberg, G. Norkrans, A. Frydén, O. Weiland, J. Kurkus, and E. Nordenfelt, J. Med. Virol. 44:272-279, 1994) allowed genotyping of 11 of 79 samples (50 of 79 samples remained unclassified by the method of Okamoto et al. In contrast, all 144 samples were genotyped by the 5'UTR assay. Forty-six of 75 (61 percent) of the samples genotyped by the method of Okamoto et al. and 10 of 11 (91 percent) of the samples genotyped by the method of Widell et al. had results consistent with those obtained by the 5'UTR assay. According to the results of direct sequencing, the method of Okamoto et al. erroneously classified seven samples as having mixed infections. In conclusion, HCV genotyping seems more reliable when it is performed by the 5'UTR assay than by either of two core region assays. The major advantage provided by the 5'UTR assay is a much lower proportion of negative or indeterminate results in younger patients with histories of drug abuse or infection by genotypes other than HCV type 1.

Objectives: This study evaluated the increase in risk of multiple births associated with ovulation induction and calculated the proportion of multiple births attributable to this treatment., Methods: Cases were 350 multiple births and controls were 737 single births enrolled from April 1993 to March 1994 in the Mercurio Project, an investigation of reproductive outcomes in Italy., Results: Ovulation induction was used in 45 case births (12.9%) and 24 control births (3.3%); the adjusted odds ratio was 4.1 (95% confidence interval [CI] = 2.4, 6.9). The odds ratio for triplet or higher order births was 72.2 (95% CI = 25.7, 202.8). When unlike-sexed multiple births were considered, the odds ratio increased for twin births, but not for triplet or higher births. The highest odds ratios were found when ovulation induction was used with assisted reproduction. The proportion of multiple births attributable to ovulation induction was 9.7% overall, 5.4% for twin births, and 69.8% for triplet or higher births., Conclusions: Ovulation induction increases the risk of multiple births and has been responsible for the rise in the rate of triplet or higher order births in Italy in the last decade. Its indiscriminate and improper use should be avoided.

We examined birthweight distribution in relation to gestational age from 25 to 42 weeks in a series of 3.526 single newborns and in whom reliability of gestational age was rigorously controlled. To verify the distribution normality the Shapiro-Wilk and the Kolmogorov tests have been applied. Birthweight data follow a gaussian distribution for each gestational age week. Therefore in the birthweight standards estimation the parametric method can safely be applied also when the series includes pathologic and preterm newborns.

A clinical and statistical study on 44 newborns of assisted conception pregnancies indicated birthweight is not significantly lower. At risk pregnancies (twins, diseases) are more frequent, as are caesarean deliveries, preterms, diseases of the newborn as malformations, particularly heart defects.

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV-associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen-antibody system, HBV-specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti-HBe in babies at birth. The data of this study indicate: 1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti-HBe-positive mothers are at a lower (P less than .01) yet consistent risk of infection. 2. HBs antigenemia is usually prolonged and symptomatic in babies born to HBeAg-positive mothers while being self-limited and asymptomatic in babies born to anti-HBe-positive mothers. 3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg-positive mothers and also in two anti-HBe-positive mothers and in one HBeAg/anti-HBe-negative mother who transmitted infection to their babies. 4. High titers of anti-HBe (up to 1:103) do not prevent HBV infection. 5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.

An investigation has been carried out on the use by parents during the first year of life of the booklet "Child health from birth to adolescence" published by the Region of Piedmont as part of a programme of preventive medicine of infancy and health education. The research was based on a questionnaire submitted to parents of 1,000 newborns, representative of the population of Turin. The results provide useful information about the development of the child and about the parent-child relationship and also on the utilisation and the utility of the booklet. The investigation also provided invaluable suggestions about modifications required in the booklet in the interests of regional programmes of preventive medicine in infancy.

The Chen method was adopted to monitor the principal congenital malformations in a large peripheric center. In 1982 two consecutive alarms showed an evident increase in the prevalence at birth of polydactylia. A retrospective analysis of the main risk factors failed to satisfactorily explain this increase.

Epidemiological data on the congenital malformations detected in 8,723 newborns over a two year period are presented.