Hepatitis C virus (HCV) genotype 1 NS5A resistance-associated variants are associated with advanced liver fibrosis independently of HCV-transmission clusters.

OBJECTIVES: The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis. METHODS: NS3/NS5A RAVs were identified by population sequencing in 387 directly acting antiviral treatment-naive G1-infected individuals (54 with genotype 1a (G1a) and 333 with genotype 1b (G1b)). Liver fibrosis was assessed based on histopathology or ultrasound elastography. Phylogenetic clusters were identified using maximum likelihood models. For statistics, chi-squared or two-sided Fisher's exact tests and multivariate logistic regression models were used, as appropriate. RESULTS: NS3 RAVs were found in 33.33% (18/54) for G1a and 2.62% (8/297) for G1b whereas NS5A variants were present in 5.55% (3/54) G1a and 9.31% (31/333) G1b sequences. Variations in NS5A 31 and 93 codon positions were found only in G1b (4.2% (14/333) for L31I/F/M and 5.39% (17/333) for Y93H). NS5A RAVs were more frequent among patients with advanced liver fibrosis (17.17% (17/99) for F3-F4 versus 6.94% (17/245) for F0-F2; p 0.004) or liver cirrhosis (20.34% (12/59) for F4 versus 7.72% (22/285) for F0-F3; p 0.003). Liver cirrhosis (F4) was associated with higher odds ratio of the NS5A RAVs among HCV-infected patients (odds ratio 2.34, 95% CI 1.004-5.291; p 0.049). NS5A RAVs were less frequent among sequences forming clusters and pairs (5.16% (8/155) versus 11.21% (26/232); p 0.039). CONCLUSIONS: Presence of NS5A RAVs correlated with progression of liver fibrosis and represents de novo selection of variants rather than transmission of drug resistance. Hence, the presence of NS5A RAVs may be a predictor for a long-lasting HCV infection.

The c.29T>C polymorphism of the transforming growth factor beta-1 (TGFB1) gene, bone mineral density and the occurrence of low-energy fractures in patients with inflammatory bowel disease.

Gastrointestinal tract conditions are frequently associated with low bone mineral density and increased risk of fractures due to osteoporosis, the latter concerning particularly inflammatory bowel disease (IBD) patients. One of the candidate genes involved in osteoporosis is the transforming growth factor beta-1 (TGFB1) whose polymorphisms may be responsible for the development of this disease. The aim of this study was to analyse the frequency of TGFB1 polymorphic variants and determine the association between the c.29T>C TGFB1 polymorphism, and bone mineral density and fractures in IBD patients. The study subjects included 198 IBD patients [100 suffering from Crohn's disease (CD) and 98 from ulcerative colitis (UC)] and 41 healthy volunteers as a control group. Densitometric bone measurements were obtained using dual energy X-ray absorptiometry. The TGFB1 genotyping was conducted using restriction fragments length polymorphism. We conducted an analysis of genotype distribution's concordance with Hardy-Weinberg equilibrium. We found statistically significant differences in lumbar spine (L2-L4) and femoral neck BMD and T-scores between CD, UC and control subgroups. The distribution of TGFB1 polymorphic variants among CD and UC patients was concordant with Hardy-Weinberg equilibrium. There were no statistically significant differences in densitometric parameters (lumbar spine and femoral neck BMD, T-score, and Z-score) between carriers of different TGFB1 polymorphisms among IBD (CD and UC) patients nor among controls. We have found no statistically significant differences in the prevalence of low-energy fractures between groups of different TGFB1 polymorphic variant carriers. The allele dose effect, recessive effect and dominant effect analysis did not show an association between low-energy fractures and the TGFB1 polymorphisms among CD and UC patients. We have not observed an association between the c.29T>C TGFB1 polymorphic variant and the bone mineral density within the cancellous and cortical bones (L2-L4 and femoral neck, respectively), or the occurrence of fractures among the IBD patients and their family members.

Bone mineral density and the 570A>T polymorphism of the bone morphogenetic protein 2 (BMP2) gene in patients with inflammatory bowel disease: a cross-sectional study.

Finding genetic predictors of osteoporosis and fractures in patients with inflammatory bowel disease (IBD) may provide incentives for non-pharmacological actions and so improve the long-term prognosis of the patients. We analysed the incidence of BMP2 570A>T polymorphic variants and their association with bone mineral density (BMD) and the incidence of fractures in patients with IBD. The study comprised 198 IBD patients (100 with Crohn's disease (CD), and 98 with ulcerative colitis, (UC)) and 41 healthy controls. Bone densitometric analysis was carried out using the DXA method. The 570A>T polymorphisms in the BMP2 gene were genotyped using RFLP. We found significant differences in the BMD and T-scores of the lumbar spine (L2-L4) and femoral neck between the three groups. In controls and CD patients, the highest L2-L4 BMD was found in carriers of the AA variant of the BMP2 gene, while among UC patients it was the case of TT carriers. In both femoral neck and lumbar spine among UC patients, the highest BMD was observed in carriers of the TT variant of the BMP2 gene. Among patients with CD and in the control group, the highest L2-L4 BMD was found in carriers of the AA variant, whereas in UC patients, it was the case of TT homozygotes. Within the femoral neck, there were no significant differences in BMD for the carriers of individual variants of BMP2 gene polymorphism. We conclude that the 570A>T polymorphism of the BMP2 gene, no statistically significant relationship was observed between the polymorphic variant and bone mineral density or the incidence of fractures in IBD patients.

Congenital Infections in Neonates of Women With Liver or Kidney Transplants.

BACKGROUND: Immunosuppressive therapy is associated with an increased risk of pregnancy complications and may have adverse effects for the newborn. The aim of this study was to determine the frequency and the type of early congenital infections and to assess typical markers of infections in neonates of liver and kidney recipients. METHODS: A retrospective analysis of 71 neonates born to either liver (39 cases) or kidney transplanted women (32 cases) was conducted. The rate and the type of newborns' infections as well as laboratory and bacteriologic markers of infections were analyzed. RESULTS: There was no significant difference in the frequency of congenital infections between the LT and KT groups (8 vs 7 cases; P = .879).). The rate of infections was not significantly higher in both groups compared with the general population. Infections were detected in 23.9%, 13.6%, and 26.6% of neonates born to mothers using tacrolimus, cyclosporine, and azathioprine respectively. No significant differences in white blood count or levels of neutrocytes and lymphocytes were observed between the groups. No abnormalities in white blood smear, but 1 case of leukopenia in the kidney transplant group, were detected. CONCLUSIONS: The rate of congenital infections in neonates of allograft recipients is not significantly higher than in the general population. Immunosuppressive regimens with azathioprine seem to carry the greatest risk, it is a little lower in the tacrolimus group, and cyclosporine-based regimens have the lowest risk of congenital infections. Differences were not statistically significant. Prenatal exposure to immunosuppressive agents seems not to be associated with any hematologic disturbances in white blood count and white blood smear.

Evaluation of selected markers of the immune system in children of renal transplant recipients.

OBJECTIVE: The aim of this study was to evaluate whether chronic use of immunosuppressive drugs during pregnancy in women after renal transplantation affects the concentration of immunoglobulin G (IgG) and IgM in the serum of their children. MATERIAL: Seventy-eight children aged 1 day to 15 years were enrolled. The study group consisted of 39 children born to renal transplant recipient mothers. The control group comprised 39 children whose mothers had not received immunosuppressive medications during pregnancy and were born at similar gestational age. METHODS: Serum concentrations of IgG and IgM were evaluated with the use of agglutination immunoassays on Siemens or Cobas device. Age-adjusted reference values for immunoglobulins formulated by Wolska-Kusnierz et al were used. Statistical analysis was performed with the use of Statistica 10.0 software with P value <.05 considered significant. RESULTS: Normal IgG concentrations were found in 82.05% (32) of children from the study group and 79.49% (31) of the control group. IgG concentrations below normal range were observed in 12.82% (5) of children from the study group and in 15.38% (6) of the control group. Normal concentrations of IgM were found in 53.85% (21) of children from the study group and in 61.54% (24) of the control group. Decreased levels of IgM were observed in 38.46% (15) of children from the study group and 35.9% (14) of the control group. There were no significant differences regarding the analyzed values between the groups. CONCLUSION: The exposure to chronic intrauterine immunosuppression had no significant effect on the concentration of IgG or IgM in children born to kidney transplant recipients.

Analysis of the selected biochemical parameters of liver and kidney function in children of mothers after liver transplantation.

INTRODUCTION: Children of mothers after liver transplantation (LT) are exposed during fetal life to the immunosuppressive agents. These drugs may have hepatotoxic and nephrotoxic effects. OBJECTIVES: The aim of the work was to assess liver and kidney parameters of children born from mothers who had LT. MATERIALS AND METHODS: The research included 51 children of mothers after LT and 51 children from a control group who were born in the First Department of Obstetrics and Gynecology in Warsaw between 2001 and 2013. The control group consisted of children born in the similar gestational age. Analysis concerned neonates, infants, and children older than 12 months. Two liver parameters (alanine transaminase [ALT] and aspartate transaminase [AST]) as well as two kidney parameters (urea and creatinine) were assessed. For statistical analysis we used Fisher's exact test and the Mann-Whitney test. RESULTS: All children from the LT group had correct ALT levels. In the control group, 5 of 51 cases (9.8 %) had levels that were greater than the norm, and those cases concerned only children younger than 12 months. The average concentration of ALT in the LT group was 15.14 U/L and the average for the control group was 22.6 U/L (P = .012699, Mann-Whitney test). Three of 51 children in the LT group (5.9%) and 8 of 51 (15.7%) in the control group had AST levels that were increased (P = .2003; Fisher's exact test). Incorrect AST levels were reported in all age groups. Incorrect values of kidney parameters concerned only neonates. Increased creatinine levels were reported in 3 of 51 cases (5.9%) in the LT group and in 1 of 51 cases (1.96%) in the control group (P = .6175; Fisher's exact test). The average concentration of creatinine in children of mothers after LT was 0.51 mg/dL, and the average of the control group was 0.44 mg/dL (P = .223698; Mann-Whitney test). Only 1 of 51 children in the LT group (1.96%) had an increased urea level. All children from both the LT and the control groups had normal ultrasound images of urinary tract and liver. CONCLUSION: Exposure to immunosuppressive drugs during fetal life does not result in the occurrence of serious disturbances of liver function and kidneys function in children of mothers after LT.

Neurological development of children born to liver transplant recipients.

INTRODUCTION: Immunosuppressive treatment used in pregnant liver recipients may have a negative impact on fetal development and successively a child. AIM: The aim of the study was to make a neurological assessment of infants and children born to liver transplant recipients (LTRs) born between December 4, 2001, and February 11, 2013, in the 1(st) Department of Obstetrics and Gynecology, Medical University of Warsaw. METHODS AND MATERIALS: The study involved 88 children, of whom 44 children were born to LTR mothers, and 44 children born to women who were not organ recipients and delivered at a similar gestational age. The gestational age of neonates ranged from 33 to 41 weeks, and the birth weight ranged from 1420 g to 4100 g. The neurological examination was performed in children from 7 weeks to 10 years of age. The neurological development was assessed by a specialist in pediatric neurology. The results of the examination were divided according to the following criteria: 1) normal development, 2) slight disorders, 3) moderate disorders, and 4) severe disorders. The Fisher's exact test was used for statistical analysis. RESULTS: Normal development was found in 35 of 44 (79.54%) children in the LTR group and 39 of 44 (88.63%) children in the control group (P = .3827). Slight disorders were observed in 6 of 44 (13.63%) children in LTR group and 5 of 44 (11.36%) children in the control group. Moderate disorders were found only in 3 of 44 (6.81%) children in the LTR group. No severe disorders were observed in both groups. CONCLUSIONS: Neurological development of children born to the liver recipients who were exposed to chronic immunosuppressive treatment in their fetal lives is the same as that of children whose mothers have not undergone organ transplantation.

[Occupational accidents in the light of the records of the Institute of Social Insurance]. / Wypadki przy pracy w swietle dokumentacji Zakladu Ubezpieczen Spolecznych.

The records of the Social Insurance Institute Department in Poznan have been used as the study material. The area of the study covered the whole province of Poznan. The study included only people employed in the State-controlled economy. Applied in the study have been certificate records of the Social Insurance Institution related to individuals applying for financial benefits and entitled to them as victims of accidents at work (health damage, disability) in 1985. The records of 3119 workers (2380 men and 739 women) were analysed. Accidents at work were found to be 2.8 times more frequent among workmen, as compared to people carrying on other than physical work. The accident rate was higher among men than among women; the difference was more distinctive in physical workers (2.7:1) than in those performing other types of work (1.3:1). 37.5% of all accidents affected the workers who had been accident victims before. A clear weekly rhythm of accidents was observed: most of them happened on Wednesday. 11 o'clock was noted as the most fatal time. Most frequent accidents were: all kinds of falls (28.8%), hand injuries (34.5%), occurring mostly during transportation or when operating a machine. In the majority of cases the accidents resulted in slight health damages; in 23.0% of victims no essential health damages were found, they were the so-called zero damages. Finger injuries occur most frequently in physical workers, whereas injuries of ankle-joints, feet and head--in those performing other types of work.