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BackgroundWe evaluated the frequency of hepatitis coinfection in Romanian adolescents who were diagnosed with human immunodeficiency virus (HIV) infection prior to 1995.MethodsOne hundred sixty-one adolescents (13–18 years of age) with symptomatic HIV infection, but without signs of hepatic dysfunction, and 356 age-matched, HIV-uninfected controls underwent laboratory testing for markers of parenterally acquired hepatitis virus infection.ResultsSeventy-eight percent of HIV-infected adolescents had markers of past or present hepatitis B virus (HBV) infection, as compared with 32% of controls (P = .0001). The prevalence of HBV replicative markers was more than 5-fold higher in HIV-infected adolescents as compared with controls: 43.4% vs 7.9% (P = .0001), respectively, for hepatitis B surface antigen (HBsAg); and 11.2% vs 2.2% (P = .0001), respectively, for hepatitis B e antigen (HBeAg). The prevalence of HBsAg chronic carriers and the presence of HBV replicative markers was significantly higher in patients with immunologically defined AIDS (CD4+ cell counts < 200 cells/mcL): 59.6% vs 34.6% (P = .02) for HBsAg and 22.8% vs 5.7%, (P = .002) for HBV DNA. After 1 year of follow-up, the proportion of those who cleared the HBeAg was considerably lower in severely immunosuppressed coinfected patients: 4.7% vs 37.1% (P = .003). Four additional HIV-infected adolescents became HBsAg-positive over the term of follow-up (incidence rate, 24.9/1000 person-years), despite a record of immunization against hepatitis B.ConclusionA substantial percentage of HIV-infected and HIV-uninfected Romanian adolescents have evidence of past or present HBV infection. In HIV-infected adolescents, the degree of immunosuppression is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease.

BackgroundPatients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.ObjectivesThe aim of this study was to investigate the possible correlations between iron metabolism serum markers, HCV viral load, and liver disease severity in treatment-naive patients with chronic hepatitis C infection.Patients and MethodsEighty five patients with untreated hepatitis C chronic infection were investigated.ResultsTwenty one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were detected in patients with severe fibrosis compared to no/mild fibrosis. Severe necroinflammatory activity was also significantly correlated with serum iron (P < 0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear regression analysis, serum levels of ferritin and transferrin were the independent variables selected as being good predictors for advanced fibrosis and severe necroinflammatory activity. No significant correlations were detected between HCV viral load and iron markers.ConclusionsThis study revealed that serum iron markers (especially ferritin and transferrin) might be used as surrogate markers for both liver fibrosis and necroinflammatory activity.Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.

AIMTo determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients.METHODSOne hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems).RESULTSOf the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P < 0.001), urban residence (P = 0.004), IL28B CC genotype (P < 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P < 0.001) and early virological response (P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P < 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%.CONCLUSIONHCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.

AbstractIn this study, we analyzed the obstetric factors affecting total nucleated cells (TNC) content of cord blood units to establish the criteria for umbilical cord blood (UCB) donor selection in our geographic area.UCB was collected from normal uncomplicated pregnancies. In every case, following data were recorded: (1) gestation length; (2) type of delivery (cesarean or vaginal); and (3) newborn characteristics: weight and sex. For each sample, TNC content, percentage and number of CD34+ cells, and viability were analyzed.The results showed that TNC content increases with cord blood volume, gestational length and newborn weight. The mean blood volume and the mean TNC per unit were 42.37 ± 13.5 ml and 55.49 ± 19.4 × 107, respectively. Stepwise regression analysis revealed a positive and significant correlation (r= 0.89) between these two variables. Meanwhile the CD34+ cell content remains unchanged in deliveries at 32–40 weeks of gestation. The mean CD34+ percentage obtained was 0.37 ± 0.06, and the total number of CD34+ cells was 4.827 ± 0.8204 × 104 / mL UCB.Concluding, the maternal and obstetric factors have a significant impact on UCB cell quantity and quality. The main criteria for UCB collection and storage resulted to be: a gestational age higher than 36–40 weeks and newborn weight > 3200g; gestation number ≤ 2 and placental weight > 700g can be added to the standard criteria to improve the bank efficiency. Our results have also become helpful in evaluating stored UCB units to establish the adequacy for clinical transplant utilization.

Previous studies of our team have shown that Romanian teenagers horizontally infected with HIV in early childhood, have a high prevalence of HBV co-infection (78.3% being anti-HBc positive vs. 21.8% of age-matched HIVnegative controls). Our aim was to investigate the frequency of mutations and variables potentially associated with an increased risk of liver disease evolution in HIV/ HBV co-infected individuals receiving 2NRTI + 1PI boosted with ritonavir. MethodsWe investigated 38 HIV+ adolescents (mean age 13.8 ± 1.3 years) with constant detectable HBV viral load, of whom 92.3% were chronic HBsAg carriers, 61.53% were HBeAg+, and 68.2% had lamivudine (LAM) in their regimen. HBV genotype was determined using commercial Line Probe Assay (Innogenetics) and sequencing of the HIV pol gene was carried out using Trugene genotyping kits (Bayer Diagnostics Inc.); for HIV subtyping the nucleotide sequences were submitted to the Stanford database.

Introduction: Chronic hepatitis C cases diagnosed in Romania were mostly related to unsafe parenteral treatments and blood transfusions; HCV genotype 1b was prevalent. During the last decade, an increasing number of HCV infections was reported among people who inject drugs (PWID). The aim of the current study was to test if this epidemiological shift triggered a diversification of the circulating viral strains. Methodology: HCV genotypes were determined by reverse hybridization in 130 HCV-infected PWID (87.7% males; mean age 27.9 ± 6.7 years, injecting drugs for 8.1 ± 4.8 years). Results: HIV-HCV co-infection was diagnosed in 80.8% of the subjects and 26.9% were HIV-HCV-HBV triple infected. Active HCV viral replication was present in 104 PWID (80%), more frequently in those HIV-co-infected (91.4% vs. 52% in HCV mono-infected, and 77.148.5% in HIV-HCV-HBV triple-infected, p = 0.0001). Non-1b genotypes were prevalent (54.8%), with subtype 1a the most commonly detected (24%), followed by genotypes 3a (14.4%) and 4 (7.7%). Mixed infections with genotypes 1a and 1b were found in nine subjects (8.7%). There was no difference in the genotypes frequencies based on HIV or HBV co-infection status, length of drug usage, or associated risk factors (tattoos, piercing, detention). Conclusion: The continuous surveillance of HCV genotypes in PWID from Romania will add valuable information to the overall European epidemiological picture, with important therapeutic implications.

AbstractDue to the increasing number of infections related to injecting drug use, both the pattern of hepatitis C virus (HCV) transmission, and the circulating genotypes in Europe have changed. As there are little available data in this respect for Romania, the aim of our study was a preliminary analysis of the distribution of HCV genotypes circulating among injecting drug users (IDUs). Of the 45 IDUs evaluated (86.7% men, mean age − 27.6 ± 3.7 years, mean age at first drug use − 17.5 ± 3.9 years), 88.9% presented anti-HCV antibodies, with higher rates in those with an injecting history of more than 10 years; 57.8% of the subjects had detectable HCV viral load. Only 6.7% had markers of chronic hepatitis B infection, and none had anti-HIV antibodies. While HCV subtype 1b is still prevalent (in 50% of the viraemic subjects), other subtypes begin to emerge, especially in younger patients (1a — in 23.1%, 4 — in 11.5%, 3a — in 7.7% of the cases). These data indicate the possibility of major shifts in the distribution of the dominant subtype, underlining the need for close surveillance of HCV infections in IDUs, who can act as a bridging group toward the general population.