HBV-DNA sequences are rarely detected in the liver of patients with HBsAg-negative chronic active liver disease and with hepatocellular carcinoma in Italy

Hepatitis B virus sequences were studied by molecular hybridization in liver biopsies from patients with HBsAg-negative chronic liver disease or hepatocellular carcinoma, collected in Italy. Among the 42 patients with chronic liver disease who had no history of drug addiction, alcohol abuse nor evidence of metabolic and autoimmune disorders, only two (5%) had HBV-DNA sequences in the liver, although 23 of them (57%) were positive for antibodies to HBV in serum. HBV-DNA was also demonstrated in integrated form in the tumorous tissue of one out of eight cases with HBsAg-negative hepatocellular carcinoma. These incidences of HBV-DNA positivity in the liver are lower than those reported from other Mediterranean areas and similar to those of North Europe, United States and Japan, suggesting that etiologic factors other than HBV are responsible for the majority of HBsAg-negative chronic liver diseases in our region.     

Tuberculosis infection and disease in immigrant children

From the second half of the eighties, the cases of tuberculosis (TBC) in Italy have been constantly increasing. The increase in TBC cases in developed countries is related to different factors, including HIV epidemic and increased number of immigrants from countries with high TBC incidence and important socio-economic problems. Compared with adults few children with TBC were homeless or coinfected with HIV, nonetheless the children lived frequently in low socioeconomic status and consequently high risk of being uninsured and with adults at risk for tuberculosis (immediate relative, household members, or recently immigrated). An epidemiologic study was carried out, in order to evaluate the impact of TBC infection in immigrant children. From January 2001 to December 2002, Mantoux test (5 IU) was performed in immigrant children hospitalized or followed in two children hospitals. They included 228 children: mean age 4 years (range 1 month to 15 years). The patients came from: South America (44%) (especially from Ecuador), from Africa (20%), from Eastern Europe (19%), (especially from Middle East and North Africa), from Far East (17%). In 30 cases (13,2%) Mantoux test was positive. Among these latter, 21 presented latent infection, whereas another 9 had tuberculous disease with pulmonary localization and one of them associated with cervical adenopathy. In the study period, among all children (4426) admitted the two Units, the prevalence of tuberculous disease was 2,5% in immigrant children compared 0.2% in native children. Accurate epidemiologic monitoring, further clinical studies aimed at highlighting TBC peculiar aspects in children, and adequate therapy can lead to TBC control in the immigrant children.     

Polyomavirus BK DNA quantification assay to evaluate viral load in renal transplant recipients.

BACKGROUND: Several studies have disclosed a correlation between polyomavirus BK (BKV) and interstitial nephritis in renal transplant recipients and its quantification in urine and serum is therefore required to assess the role of BKV infection in nephropathy. OBJECTIVE: This paper describes a urine and serum BKV-DNA quantification protocol devised to evaluate the viral load. STUDY DESIGN: Screening of samples containing > or =10(3)/ml viral genome copies by a semi-quantitative polymerase chain reaction (PCR) assay is followed by precise quantification of the samples containing a high number of viral genomes in a quantitative-competitive (QC)-PCR assay. Generation of the competitor construct relied on the different sizes of wild-type and competitor amplicons. RESULTS AND CONCLUSIONS: Screening by semi-quantitative PCR selects samples with a high number of viral genomes for use in the more labor-intensive and -expensive QC-PCR assay and thus provides a handy means for quantitative DNA analysis of large numbers of samples. The results obtained in BKV-DNA quantification in urine and serum samples from 51 renal transplant recipients (22 on treatment with tacrolimus (FK506) and 29 on cyclosporine A (Cy A)) are interesting: BKV-DNA findings (43.1%) in urine samples are in agreement with the BKV urinary shedding reported in literature (5-45%). With regard to immunosuppressive treatment, the percentage of activation of the infection (revealed by BKV-DNA detection in urine samples) in the two groups of therapy is similar (40.9% vs 44.8%). The observation that the viral load in urine is dissociated with that of serum suggests that both parameters should be investigated in evaluation of the pathogenetic role of BKV reactivation in renal transplant recipients. Moreover, our BKV-DNA quantification protocol could be used to monitor viral load in urine and serum samples from renal transplant recipients so as to detect those at risk of nephropathy and monitor their response to immunosuppression reduction therapy if it occurs.     

Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus

Objective: To evaluate the clinical, biochemical, and virologic features associated with hepatitis C virus (HCV) infection acquired early in life from mothers with antibodies to HCV (anti-HCV).Study design: Multicenter prospective-retrospective study in Italian children.Patients: Two groups of children were investigated. Group 1 included 14 infants, born to mothers with anti-HCV but without human immunodeficiency virus infection, who became seropositive for HCV RNA during the first year of life and were thus considered infected. Group 2 included 16 children with chronic hepatitis C, aged 1 ½ to 14 years, whose mothers were the unique potential source of infection. Both groups were followed for 12 to 48 months.Methods: Alanine transaminase (ALT), anti-HCV, and HCV RNA were investigated by the polymerase chain reaction on entry to the study and during follow-up.Results: All children in group 1 had anti-HCV throughout follow-up, and all had ALT abnormalities, ranging from 1.5 to 10.5 times the normal value during the first 12 months. During further follow-up, 5 of 10 children had HCV RNA with abnormal ALT values, 3 had a return to normal of the ALT values but continued to have viremia, and 2 eventually had normal ALT values and clearance of HCV RNA. Of the 16 children in group 2, all were free of symptoms and 62% had only slight ALT elevations; 7 who underwent liver biopsy had histologic features of minimal or moderate hepatitis.Conclusions: HCV infection acquired early in life from mothers with anti-HCV is usually associated with biochemical features of liver damage during the first 12 months of life. Progression to chronicity seems to occur in the majority of cases, although HCV-associated liver disease is likely to be mild throughout infancy and childhood. (J Pediatr 1997;130:990-3)     

Hepatitis C virus genotypes in chronic hepatitis C of children

SUMMARY. Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 3 3 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype Ib was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype la (16.6%), genotype 2 (11.1%). and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.     

Incidence of new diabetic patients on dialysis in Piedmont,Italy: Major changes recorded over a 10-year period

Different incidence rates of new diabetic patients on dialysis are reported in various settings; although prevalence of this disease is often considered a marker of acceptance policy, rates are thought to be influenced also by genetic, epidemiological and other characteristics of a population (genetic composition, age distribution, lifestyle). Moreover, since features of a general population are often not stable (as in the setting analysed) changes at this level may have important reflections in the incidence of diabetics with end-stage renal disease (ESRD). In the region studied (Piedmont, northern Italy, about 4400 000 inhabitants, 20 dialysis centres, open acceptance since the mid-1970s, yearly information on 100% of patients, gathered by a Dialysis and Transplantation Registry) the incidence of diabetic patients with ESRD (389 cases recorded 1981–1990: 222 males, 167 females: mean age at start increasing from 55.5 years in 1981–1985 to 58.7 years in 1986–1990) differs according to age and sex. Incidence was higher in males, and rose from 6.23/year patients per million population (p.m.p.) in 1981–1982 to 12.88/year p.m.p. in 1989–1990, with a peak at age 60–69 (from 18.46/year p.m.p. in 1981–1982, to 46.12/year p.m.p. in 1989–1990). While relatively stable in the younger age groups from 1981 to 1990, incidence increased in the elderly (males age 70–79: 7.12/year p.m.p. in 1981–1982, 26.08/year p.m.p. in 1989–1990). As regards clinical and metabolic patterns, at the first update, in 1986–1990, 88.3% of diabetic patients were hypertensive or taking hypotensive drugs; albumin levels were below the normal range (<3.5 g/dl) in 30.3%; cholesterol levels were below the normal range (<150 mg/dl) in 16.15%. As regards entry criteria, creatinine clearances ranged from <1 to 14 ml/min (mean values at first update: 3.45±2.76 ml/min). In conclusion, presentation of diabetic patients with ESRD is changing. The stability of incidence in the younger age groups confirms the appropriateness of an open acceptance policy, at least for these ages. The increase in the elderly probably reflects the longer lifespan of diabetic patients in the overall population, while the influence of a hidden preselection must be further assessed. Since this cohort increasingly requires in-hospital high-tolerance treatment, future provision of dialysis needs must take into account the trend towards an increase in this high-risk elderly population.     

Transmission of hepatitis C virus from infected mother to offspring during subsequent pregnancies

BACKGROUND: Several studies have demonstrated that hepatitis C virus (HCV) may be transmitted from mother to offspring. To date, however, little is known about the risk of vertical transmission during subsequent pregnancies. The purpose of this study was to evaluate the risk of vertical HCV transmission in offspring in subsequent pregnancies of HCV infected women. METHODS: In a multicenter study, two groups of index cases were selected. Group 1 included 75 children investigated for HCV infection during prospective studies of vertical transmission. Group 2 included children born to HCV-infected mothers and found to be HCV infected, independent of studies on vertical transmission. All children in the index cases had one or more siblings. Anti-HCV, HCV-RNA (determined by polymerase chain reaction), and HCV genotype were evaluated in all the infected children, their mothers, and siblings. RESULTS: The results indicate that a mother who has already delivered an HCV-infected baby is not at greater risk of infecting her second child. Duration of maternal infection does not seem to be a risk factor in offspring infection, because HCV infection is equally distributed among first-born infants and infants of subsequent births. Because clustering of HCV infection among siblings appeared to be rare in this study, data also indirectly confirm that the risk of horizontal transmission of HCV among siblings is low. CONCLUSION: For practical purposes, the current observations indicate that mothers who have already delivered an HCV-infected child can be advised that this event does not increase the probability of infecting the second child.