Neurocognitive and Motor Functions in Biliary Atresia Patients: A Cross-sectional, Prospective National Cohort Study.

OBJECTIVES: The aim of the study was to evaluate the neurocognitive and motor development of biliary atresia (BA) patients in childhood and adolescence and to identify risk factors for impaired outcome. METHODS: We invited all BA patients between ages 1 and 20 years followed up at Helsinki University Children's Hospital in Finland between 1 January 2019 to 31 January 2020 to participate. All participants underwent age-appropriate validated neurocognitive tests. Participants between 3.0 and 16.9 years of age were assessed with the Movement Assessment Battery for children, version 2. Guardians of participants between ages 5 and 17 years filled the Five-to-Fifteen-Revised (5-15R) parental questionnaire. RESULTS: The mean (±standard deviation [SD]) total intelligence quotient (IQ) of the 39 participants was 91 ±â€Š15, lower compared with test norms (mean IQ 100 ±â€Š15, P < 0.01). Earlier clearance of jaundice (COJ) had a positive effect on mean (±SD) total IQ (COJ <3 months 96 ±â€Š13 vs COJ ≥3 months post-portoenterostomy 84 ±â€Š13, P < 0.05). Out of 30 participants assessed, 13 (43%) were either at risk or fulfilled the criteria for impaired motor development. Guardians reported elevated rates of functional difficulties affecting everyday life. There were no significant differences between native liver and liver transplanted (16/41%) groups. CONCLUSIONS: IQ is moderately, and motor scores markedly impaired in BA patients compared with normative data. Standardised cognitive and motor assessment before school-age for all BA patients is advisable to identify individuals in need of additional support.

Impaired Bone Health in Children With Biliary Atresia.

OBJECTIVES: The aim of the study was to examine the frequency of rickets and bone fractures and to assess areal bone mineral density (aBMD) in childhood among patients with biliary atresia (BA). METHODS: We gathered data on all patients diagnosed with BA in Finland that survived to ≥1 year of age between 1 January 2000 to 30 June 2018. Data on gestational age, birth weight, postsurgical medications, and history of rickets and bone fractures were collected retrospectively. Serum levels of 25-hydroxyvitamin D [25(OH)D] postportoenterostomy (PE) were collected. Plain radiographs and dual energy X-ray absorptiometry (DXA) measurements of study subjects were reviewed. RESULTS: Out of 49 patients, 7 (14%) were diagnosed with rickets during infancy. Clearance of jaundice [odds ratio 0.055, 95% confidence interval [CI] 0.00266-0.393; P < 0.01] was a protective factor against rickets. Sufficient 25(OH)D levels were reached 3 months post-PE. Eleven (22%) patients suffered at least one bone fracture (range 1-9) during childhood and adolescence. In DXA measurements, median lumbar spine aBMD anthropometrically adjusted z-scores were as follows: in native liver survivors 0.8 (interquartile range [IQR] -1.9 to 1.4) at 5 and -0.3 (IQR -1.3 to 0.8) at 10 years and for liver transplanted patients 0.4 (IQR -0.2 to 1.1) at 5 and 0.6 (IQR -0.1 to 1.3) at 10 years. CONCLUSIONS: BA patients have an increased risk for rickets and bone fractures compared with the normal population. Most BA patients have aBMD within normal range between 5 and 10 years of age irrespective of liver transplantation status.

Growth of children with biliary atresia living with native livers: impact of corticoid therapy after portoenterostomy.

We addressed growth of biliary atresia (BA) patients living with native livers between ages 0-6 and effects of post-surgical corticosteroid treatment on growth. Growth charts of 28 BA patients born in Finland between 1987 and 2017 were retrospectively evaluated. Dosage and length of corticosteroid treatment and hydrocortisone substitution were reviewed. At birth, BA patients were shorter (median height - 0.6 (interquartile range (IQR) - 1.3 to - 0.1) SDS, n = 28, P < 0.001) than general population. Height remained stable during early childhood (median height - 0.6 (IQR - 1.4 to 0.1) SDS for girls and - 0.4 (IQR - 1.6 to 0.2) SDS for boys at 6 years of age). Patients were of normal height adjusted weight at 6 years with a median age and sex-adjusted body mass index (ISO-BMI) of 20.9 (IQR 19.3 to 25.0) for girls and 22.1 (IQR 20.7 to 25.6) for boys. Higher (≥ 50 mg/kg) cumulative post-portoenterostomy prednisolone dosage resulted in 0.18 SDS lower height per treatment week (ß - 0.18, SE 0.04, P < 0.001) compared to lower dosage (< 50 mg/kg).Conclusion: BA patients grow normally during early childhood. As high postoperative corticosteroid dosage has a short-term negative effect on height, very high dosages should be avoided. What Is Known: • Growth of biliary atresia patients has mostly been shown to be within normal limits • Corticosteroids may decrease growth rate What Is New: • Biliary atresia patients surviving with their native livers are shorter than general population and their mid-parental target height at birth • A high (> 50 mg/kg) cumulative prednisolone dosage has a negative transitory impact on height gain after portoenterostomy.

Long-term outcomes of biliary atresia patients surviving with their native livers.

Portoenterostomy (PE) has remained as the generally accepted first line surgical treatment for biliary atresia (BA) for over 50 years. Currently, close to half of BA patients survive beyond 10 years with their native livers, and most of them reach adulthood without liver transplantation (LT). Despite normalization of serum bilirubin by PE, ductular reaction and portal fibrosis persist in the native liver. The chronic cholangiopathy progresses to cirrhosis, complications of portal hypertension, recurrent cholangitis or hepatobiliary tumors necessitating LT later in life. Other common related health problems include impaired bone health, neuromotor development and quality of life. Only few high-quality trials are available for evidence-based guidance of post-PE adjuvant medical therapy or management of the disease complications. Better understanding of the pathophysiological mechanisms connecting native liver injury to clinical outcomes is critical for development of accurate follow-up tools and novel therapies designed to improve native liver function and survival.

An association between manganese superoxide dismutase polymorphism and outcome of chemotherapy in acute myeloid leukemia.

Manganese superoxide dismutase (MnSOD) protects cells against oxidative stress by eliminating superoxides. Hypothetically, decreased MnSOD levels in cancer might lead to increased oxidative stress and, thus, to increased sensitivity of cells to chemotherapy agents. Eighty-nine patients with acute myeloid leukemia (AML) were analyzed for a functional C to T polymorphism of MnSOD, which could potentially lead to decreased enzyme concentrations inside mitochondria. A significant survival advantage (p=0.02) was observed for those AML patients carrying T-containing alleles of MnSOD compared to the patients with the CC genotype. These preliminary results may indicate an important role for genetic factors regulating the cellular redox state in determining the outcome of leukemia chemotherapy.