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Biomedical subjects

William F Balistreri

Publications and source records attributed to William F Balistreri.

At least 19 recordsLinked to original sources
PubMed2007

High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease.

OBJECTIVE: Alpha-1-antitrypsin (A1AT) deficiency is the most common genetic cause of liver disease in children; however, the role of polymorphic heterogeneity in the A1AT gene as a modifier of other forms of pediatric liver disease is not clear. We hypothesized that non-M A1AT allele variants are more common in children with chronic liver disease than in the general population. METHODS: A retrospective, single-center study was performed in which A1AT phenotypes were obtained by reviewing charts of children with chronic liver disease. Chi-square analysis was used to compare allele frequencies in the population of children with liver disease with published epidemiologic data and to compare allele frequencies among disease subgroups. RESULTS: The frequency of A1AT Z and other alleles was increased in children with chronic liver disease (n = 241) when compared with the published reference database (P < 0.001). This increase remained significant when the population was divided into disease subsets: biliary atresia (n = 67) and other liver disease (n = 174) (P < 0.001 for both). Among children with biliary atresia referred for liver transplant evaluation, the presence of a non-M allele was associated with a lower mean age at transplant listing than the MM phenotype (235 vs 779 days, P = 0.036) and more frequent loss of native liver by 24 months of age (90% vs 65%, P = 0.04). CONCLUSIONS: A1AT non-M alleles are more frequent in children with chronic liver disease than in the general population. We speculate that these non-M alleles may act as genetic modifiers in pediatric liver disease in general and modulate disease progression in children with biliary atresia in particular.

Child↗
PubMed2006

Whatever happened to "neonatal hepatitis"?

'Idiopathic neonatal hepatitis' is a term that has traditionally been used to denote a clinical syndrome manifest by prolonged jaundice in the neonate. This description is now used much less frequently because recent studies unite well-defined clinical, biochemical and molecular features of intrahepatic cholestasis into specific syndromes. Advances in the understanding of the molecular basis of cholestatic syndromes now enable the classification of syndromes based on biology and offer an opportunity to develop new diagnostic approaches and treatment strategies that take into account the genetic make-up of the child with cholestasis.

Bile↗
PubMed2006

An enteric-coated high-buffered pancrelipase reduces steatorrhea in patients with cystic fibrosis: a prospective, randomized study.

OBJECTIVE: Enteric-coated (EC) high-buffered (2.5 mEq [2.5 mmol] bicarbonate per capsule) pancrelipase microsphere enzymes were compared to EC-nonbuffered pancreatic enzymes for efficacy in reducing steatorrhea in patients with cystic fibrosis. DESIGN: Prospective, randomized, controlled trial using a crossover design with each subject as his/her own control. SUBJECTS/SETTING: Eighteen subjects with cystic fibrosis, who had pancreatic insufficiency and required large enzyme doses, were studied over two consecutive 7-day treatment periods. INTERVENTION: Each 7-day period consisted of 3 days at home followed by 4 days in a general clinical research center for careful control of diets, enzyme lipase doses (given at approximately 50% of the subject's usual lipase dose), and carmine red-labeled stool collections for 72-hour fecal fat balance studies. MAIN OUTCOME MEASURE: Fecal fat excretion. STATISTICAL ANALYSES PERFORMED: Differences in fat excretion, when each subject received EC-high-buffered pancrelipase vs EC-nonbuffered enzymes, were compared using linear modeling. RESULTS: Mean fat excretion decreased significantly in each subject during periods when given EC-high-buffered pancrelipase compared with periods when given EC-nonbuffered enzymes (fat excretion 18.2% vs 24.9% or fat absorption 81.8% vs 75.1%, respectively; P=0.01). Thirteen of 18 subjects (72%) excreted less fat when receiving EC-high-buffered pancrelipase whereas 10 (56%) decreased fat excretion by more than 5%, and five subjects did not respond. CONCLUSIONS: EC-high-buffered pancrelipase decreased fat excretion, symbolizing improved fat absorption, when compared with EC-nonbuffered pancreatic enzymes given at equivalent, reduced (approximately 50% of usual) lipase doses in nourished subjects with cystic fibrosis and mild pulmonary disease.

Adolescent↗
PubMed2006

High prevalence of renal dysfunction in long-term survivors after pediatric liver transplantation.

OBJECTIVE: To determine the prevalence and identify variables associated with renal dysfunction in long-term survivors of pediatric liver transplantation. STUDY DESIGN: Data from 117 patients who survived>or=3 years after liver transplantation were analyzed. Demographic and clinical information was obtained from chart review and from a clinical care database. The dependent variable was renal function as determined by measured glomerular filtration rate (mGFR). Univariate and multivariate analyses were performed to identify independent variables associated with renal dysfunction (mGFR<70 mL/min per 1.73 m2). RESULTS: The average time since liver transplant was 7.6+/-3.4 years (range, 3 to 14.6 years). When the last available mGFR for all patients was analyzed, renal dysfunction was present in 32%. In the univariate analysis, mGFR at 1 year after transplant, cyclosporine immunosuppression, and time since transplant were significant; the second two were strongly collinear. Using multiple logistic regression modeling excluding time since transplant, cyclosporine and mGFR at 1 year after transplant were strongly associated with renal dysfunction. CONCLUSIONS: Renal dysfunction is a common complication in children who survive liver transplantation. Our observations are of critical importance because children may live long enough to move from a stage of renal insufficiency characterized by asymptomatic decreased GFR to symptomatic end-stage renal disease.

Adolescent↗
PubMed2005

Treatment options for chronic cholestasis in infancy and childhood.

Altered bile flow physiology leads to many complications commonly seen in patients with cholestatic liver disease, regardless of the etiology. For each individual patient, a coordinated and effective treatment strategy must address the presence and the severity spectrum of malabsorption, malnutrition, vitamin and micronutrient deficiencies, pruritus, xanthomata, ascites, and liver failure, which are attributed directly or indirectly to diminished bile flow. An aggressive approach to maximizing the nutritional status of the child is vital to ensure optimal growth and development. Protein-calorie and/or fat supplementation is best discussed early. Decreasing the percentage of dietary long-chain triglycerides, providing medium-chain triglycerides, and ensuring adequate essential fatty acid and adequate protein intake may be helpful. Fat-soluble vitamin (A, D, E, and K) levels and micronutrient levels must be carefully and serially monitored and supplemented as necessary. Because the mechanisms that mediate pruritus of cholestasis remain to be determined, the use of empirical therapies continues to be standard practice. Ursodeoxycholic acid may ameliorate pruritus. Antihistamines and rifampicin may also provide temporary relief for some children. Based on the evidence that increased central opioidergic tone is present in chronic cholestasis, the use of opiate antagonists is promising but has not been evaluated in children. Selected patients with refractory pruritus that have failed maximal medical therapy have benefited from partial external biliary diversion. Ongoing dialogue with the family regarding the indications for liver transplantation is reasonable. Optimization and adherence with the pretransplant medical management enhance the chances for a successful outcome from liver transplantation. Specific to the pediatric patient, optimizing growth, development and nutrition, minimizing discomfort and disability, and aiding the child and family in coping with the stress, social, and emotional effects of chronic liver disease remain paramount.

Journal Article↗
PubMed2004

Bile acid synthetic defects and liver disease: a comprehensive review.

Bile acid synthetic defects (BASD), uncommon genetic disorders that are responsible for approximately 2% of persistent cholestasis in infants, are reviewed with emphasis on morphology of associated liver disease. The associated liver diseases may be life threatening, and are treatable, usually by replacement of deficient primary bile acids. Specific diagnosis is made by analysis of body fluids (bile, blood, and urine) using fast atom bombardment-mass spectroscopy (FAB-MS) and gas chromatography-mass spectroscopy (GC-MS). Inborn errors have been demonstrated for four single enzymes involved in modification of the sterol nucleus and in five steps in modification of the side-chain to form cholic and chenodeoxycholic acids, the primary bile acids. With few exceptions, BASD cause liver diseases that vary from severe to mild depending on the defect. In three of four known defects of sterol nucleus modification, liver disease is progressive. Progression of liver disease is most rapid when the defect results in accumulation of toxic monohydroxy and unsaturated oxo-bile acids. Liver disease may be transient, delayed in onset and mild. Reduced bile flow caused by atypical bile acids contributes to cholestasis and may be the dominant factor in defects of side-chain synthesis, peroxisomal abiogenesis and S-L-O syndrome. Pathological findings may include intralobular cholestasis with giant cell transformation, prevalence of necrotic hepatocytes including giant cell forms, and hepatitic injury confined to the portal limiting plate where the smallest bile ductules may be injured and where fibrosis typically develops. Interlobular bile ducts are usually spared. Ultrastructure of liver reveals nonspecific changes with the possible exception of unusual canalicular morphology in some defects. The course of BASD may be modified by replacement of deficient primary bile acids, which produces beneficial feedback inhibition of abnormal bile acid production and enhances choluresis. Giant cell transformation is present in all symptomatic infants with BASD and seems to have a more consistent association with BASD than with the many other liver diseases in infants where it occurs. We hypothesize that immature hepatocytes of infants may fuse to form multinucleate hepatocytes whenever atypical or toxic bile acids are present and the pool of normal bile acids is critically reduced.

3-Hydroxysteroid Dehydrogenases↗
PubMed2004

Outcome after pediatric liver transplantation impact of living donor transplantation on cost.

OBJECTIVE: To compare the direct health care cost of living donor liver transplantation (LDLT) with that of cadaver donor liver transplantation (CDLT) in children and identify predictors of cost. STUDY DESIGN: All 16 children who underwent LDLT from January 1997 through January 2002 at Cincinnati Children's Hospital Medical Center comprised the study population. They were matched for age, diagnosis, and nutritional status with 31 children who received CDLT during the same era. A historic cohort analysis was performed. RESULTS: There was no difference in the 1-year mortality rates between both groups. Costs associated with graft retrieval contributed 15.3% and 31% of the initial transplant cost for LDLT and CDLT, respectively. Mean cost of care in the first year was 60.3% higher for LDLT than CDLT (P=.01). Multivariate analysis identified biliary complications and insurance status as predictors of cost for initial transplantation (R(2)=0.57), whereas biliary complications and pediatric end stage liver disease scores were identified as predictors of cost of care in the first year after transplantation (R(2)=0.77). CONCLUSIONS: The comprehensive cost of LDLT in the first year after transplantation is higher than cadaveric transplantation. This must be balanced against the time spent and care needs of patients on the waiting list.

Cadaver↗
PubMed2004

Impact of liver transplantation on HRQOL in children less than 5 years old.

Our primary goal was to assess health related quality of life (HRQOL) at transplantation and 1 yr after transplantation in pediatric liver transplant patients aged less than 5 years. We conducted a prospective longitudinal study of HRQOL in pediatric liver transplant recipients, aged less than 5 years to define the impact of liver transplantation on HRQOL and identify factors that predict HRQOL after transplantation. The infant toddler health status questionnaire (ITHQ) was completed at the time of listing for liver transplantation and at 6 and 12 months after liver transplantation. The primary outcome measures were the subscale scores that comprise ITHQ. The mean age (+/-s.e.m.) of the enrolled patients (n = 45) at transplantation was 1.4 (+/-1.2) yr. Thirty-eight (84%) of the enrolled patients completed the study. The highest mean baseline scores of 78.6 (+/-3.3) were for global mental health (GlobalMH). ITHQ subscale scores increased steadily after transplantation. The greatest increase was in the first 6 months after transplant. At 1 yr after transplantation, there were significant increases in all of the ITHQ subscale scores except for GlobalMH. ITHQ subscales were similar for patients who received LDLT compared with those who received cadaver donor liver transplantation (CDLT) at baseline and a year after transplant. Time elapsed as transplantation was a significant predictor of functional health in all of the models generated. Scores for general health (GH), global health (GGH), parental time-impact (PT) and parental time-emotion (PE) were higher for male children. Family cohesion (FC) improved with time elapsed since transplant and increased number of inpatient days. HRQOL improves after transplantation in all of our patients irrespective of the donor type. Functional health scores were higher in patients with normal serum bilirubin at 1 yr post-transplant. Assessment of HRQOL should be an integral part of care for liver transplant patients and their caregivers.

Bilirubin↗
PubMed2003

Determination of risk factors for Epstein-Barr virus-associated posttransplant lymphoproliferative disorder in pediatric liver transplant recipients using objective case ascertainment.

BACKGROUND: Previous studies have suggested an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD) in patients receiving tacrolimus for immunosuppression. We hypothesized that after correction for confounding variables, immunosuppression with tacrolimus is not associated with an increased risk of EBV-PTLD. METHODS: Potential cases of EBV-PTLD, identified by chart review, were independently ascertained by three clinicians and defined using published criteria. Agreement in diagnosing EBV-PTLD was measured using Kappa coefficients. Unadjusted and adjusted relative risk estimates were determined using proportional hazards regression. RESULTS: Twenty-three cases of EBV-PTLD were identified in 221 patients, a proportion of 10.4% (95% confidence interval [CI]: 6.4%-14.4%). Multivariable analysis revealed that immunosuppression with tacrolimus was associated with an increased risk of EBV-PTLD (relative risk 3.10: 95% CI: 1.21-7.92), as was age at transplantation as a continuous variable (parameter estimate -0.15, P=0.03). Kappa coefficients in diagnosing EBV-PTLD and subclassifying as neoplastic and non-neoplastic EBV-PTLD were 0.73 (95% CI: 0.54-0.93) and 0.54 (95% CI: 0.40-0.68), respectively. Patients with neoplastic PTLD demonstrated a lower probability of survival than patients with non-neoplastic PTLD and non-cases. CONCLUSIONS: Immunosuppression with tacrolimus and young age at transplantation are associated with an increased risk of EBV-PTLD in children undergoing liver transplantation, although we cannot exclude detection bias as an explanation for this observed increase. Good agreement between observers can be achieved using previously published criteria for defining EBV-PTLD. Patients with neoplastic EBV-PTLD may have a worse prognosis, and thus identification of risk factors for the development of this subtype of the disorder may be more important.

Aging↗
PubMed2003

Risk of hearing impairment in pediatric liver transplant recipients: a single center study.

As survival rates following liver transplantation have increased, health care providers must assess the impact of transplantation on dimensions other than traditional medical measures. Hearing impairment may adversely impact social, emotional, cognitive, academic, and speech and language development. We hypothesized that children who undergo liver transplantation are at risk for hearing impairment due to exposure to ototoxic drugs. We conducted a review of 74 children who had undergone liver transplantation between December 1996 and September 2000 at Cincinnati Children's Hospital Medical Center. Hearing was assessed at discharge by an audiologist using age and developmentally appropriate techniques. The principal outcome measure was sensorineural hearing impairment. Independent variables were age at transplantation, United Network for Organ Sharing (UNOS) status at transplantation, primary diagnosis, post-transplant length of hospital stay, days of treatment with aminoglycosides, and days of treatment with loop diuretics. Eleven of 74 children (15%) had sensorineural hearing loss, of whom four had severe to profound hearing loss. Multivariate analyses showed that the adjusted relative risk for hearing loss in patients with hepatoblastoma was 66 and that there was a 5% increase risk for hearing loss for each additional day of hospitalization. Age at transplantation, UNOS status, and days of treatment with loop diuretics or aminoglycosides did not achieve significance in the model. Sensorineural hearing impairment occurs in a subset of pediatric patients following liver transplantation. Patients with hepatoblastoma or those who experience prolonged hospitalization after transplantation are at increased risk. Our observations are of particular importance for pediatric liver transplant recipients since the median age at transplantation is 12-18 months, a critical period for language acquisition.

Biliary Atresia↗
PubMed2003

Health-related quality of life in pediatric liver transplant recipients: A single-center study.

The goals of the present study were (1) to measure health-related quality of life (HRQOL) in pediatric liver transplantation (LT), (2) to identify demographic and clinical factors that correlate with HRQOL, and (3) to compare two instruments that have been used to measure HRQOL in children and adolescents. We conducted a single-center cross-sectional study of 77 pediatric LT recipients ages 5 to 18 years, all of whom had had LT at least 6 months previously. We used the Child Health Questionnaire Parent Form 50 (CHQPF50) and the PedsQL4.0 to determine measured dimensions of physical and psychosocial health from the parents' perspective. Individual scale scores range from 0 to 100, with higher scores reflecting better health. Data on demographics, clinical status at transplantation, posttransplantation clinical course, and graft function were collected to identify predictors of posttransplantation HRQOL. Fifty-three percent of the liver transplant recipients had biliary atresia, 78% were white, and 61% were female. The mean age at LT was 3.8 +/- 3.6 years, and the range of time since LT was 1 to 15 years. HRQOL in pediatric liver transplant recipients was lower than that reported for healthy children but similar to that for children with other chronic illness. Age at transplantation, the time elapsed since transplantation, hospitalizations within the previous year, maternal education, and race were significant predictors of physical health. Age at transplantation and maternal education predicted psychosocial function. HRQOL was decreased in a population of pediatric liver transplant recipients compared with the general population and similar to that for children with chronic illness. Prospective longitudinal studies will permit us to define predictors of HRQOL at different periods of time after transplantation. The information gained from this study will help us to better define expectations and the clinical course after liver transplantation to patients and their families.

Adolescent↗
PubMed2003

Bone mineral density in long-term survivors following pediatric liver transplantation.

We sought to estimate the prevalence of reduced bone mass, defined by lumbar spine bone mineral density (LS-BMD) (z-score < -2.0), and to determine the factors associated with LS-BMD after liver transplantation in children and adolescents. LS-BMD z-scores were measured in a sample of subjects who had undergone liver transplantation in childhood or adolescence using dual energy x-ray absorptiometry (DXA). One hundred nine patients underwent DXA. The mean age at transplantation was 4.3 years (median, 1.8 years), and mean duration since transplantation was 6.2 years (median, 5.8 years). The mean weight z-score was -0.130 (SD, 1.26). The mean LS-BMD z-score was -0.243 (SD, 1.27). Eight patients, or 7.3% (95% confidence interval [CI], 2.4% to 12.2%), had reduced bone mass. Compared with those without reduced bone mass, subjects with reduced bone mass were more likely to have been treated for rejection at least once (87.5% versus 51.5%; P =.07), and had greater cumulative exposure to prednisone during the year before DXA (92.3 versus 26.2 mg/kg/y; P =.001). Multiple linear regression determined that LS-BMD z-score was positively associated with time since transplantation and weight z-score and negatively associated with cumulative prednisone exposure. Serum 25-OH vitamin D was measured and reduced (< 15 ng/mL) in 5 of 87 patients, one of whom had reduced bone mass. In conclusion, the prevalence of reduced bone mass was 7.3% in our population. Only certain patients appear to be at risk for low BMD, including those with a history of rejection. Screening for reduced bone mass may be appropriate for these patients.

Absorptiometry, Photon↗
PubMed2002

Pediatric liver disease in the United States: epidemiology and impact.

Liver diseases which affect children are unique. Diseases such as inborn errors of metabolism are fertile grounds for investigation. Study of these 'experiments of nature' will provide insight into hepatobiliary function and lead to novel treatment modalities. Successful treatment or prevention of liver disease in children will have long-term implications. This report describes the current burden of pediatric liver disease and offers approaches to intervention.

Child↗