Lamivudine, Entecavir, or Tenofovir Treatment of Hepatitis B Infection: Effects on Calcium, Phosphate, FGF23 and Indicators of Bone Metabolism

ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

Severe asymptomatic hypophosphataemia in a child with T-acute lymphoblastic leukaemia

Hypophosphataemia is a metabolic disorder that is commonly encountered in critically ill patients.Phosphate has many roles in physiological functions, thus the depletion of serum phosphate could leadto impairment in multiple organ systems, which include the respiratory, cardiovascular, neurologicaland muscular systems and haematological and metabolic functions. Hypophosphataemia is defined asplasma phosphate level below 0.80 mmol per litre (mmol/L) and can be further divided into subgroupsof mild (plasma phosphate of 0.66 to 0.79 mmol/L), moderate (plasma phosphate of 0.32 to 0.65mmol/L) and severe (plasma phosphate of less than 0.32 mmol/L). The causes of hypophosphataemiainclude inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphateloss, and redistribution of phosphate into cells. Symptomatic hypophosphataemia associated withhaematological malignancies has been reported infrequently. We report here a case of asymptomaticsevere hypophosphataemia in a child with acute T-cell lymphoblastic leukaemia.A 14-year-old Chinese boy was diagnosed to have acute T cell lymphoblastic leukaemia (ALL).His serum biochemistry results were normal except inorganic phosphate and lactate dehydrogenaselevels. The serum inorganic phosphate level was 0.1mmol/L and the level was low on repeatedanalysis. The child had no symptoms related to low phosphate levels. The possible causes of lowphosphate were ruled out and urine Tmp/GFR was normal. Chemotherapy regime was started andthe serum phosphate levels started to increase. Hypophosphataemia in leukaemia was attributed toshift of phosphorus into leukemic cells and excessive cellular phosphate consumption by rapidlyproliferating cells. Several reports of symptomatic hypophosphataemia in myelogenous andlymphoblastic leukaemia in adults have been reported. To our knowledge this is the first case ofsevere asymptomatic hypophosphataemia in a child with ALL.

Perfil bioquímico en sangre de cordón en prematuros extremos y crecimiento fetal / Intrauterine growth and biochemical levels in cord blood samples in infants less than 31 weeks gestation

Introducción: Con mayor aporte de proteínas y energía en la primera semana se ha observado hipofosfemia en prematuros extremos. Los menores niveles de fósforo se han presentado en prematuros con antecedentes de restricción de crecimiento intrauterino. Objetivos: Caracterizar los niveles plasmáticos bioquímicos en el cordón de prematuros extremos, nacidos adecuados (AEG) y pequeños para edad gestacional (PEG) y la relación con calcemia y fosfemia en la primera semana de vida. Pacientes y método: Estudio clínico realizado en Neonatología del Hospital Doctor Sótero del Río, en los años 2013 y 2014. Se analiza el perfil bioquímico en el cordón y la calcemia y fosfemia en los primeros 7 días de vida, registrados en la ficha clínica según fueran AEG o PEG, según las curvas de Alarcón-Pittaluga. Análisis con significación de p < 0,05. Resultados: Los niveles de colesterol, transaminasas, albúmina y creatinina fueron similares para los PEG y AEG. Los niveles de pH, fósforo, calcio, y fosfatasas alcalinas fueron menores en los PEG. El nitrógeno ureico, el ácido úrico y los triglicéridos fueron mayores en los PEG. Los PEG muestran marcada reducción de fosfemia en la primera semana, la calcemia tiende a subir proporcionalmente al descenso de la fosfemia. Conclusiones: En prematuros extremos la desnutrición intrauterina se expresa en modificación de los niveles plasmáticos de calcio, fósforo, fosfatasas alcalinas, nitrógeno ureico, ácido úrico y triglicéridos. Posnatalmente, al recibir aporte nutricional, se manifiesta una disminución de la fosfemia y un aumento de calcemia, concordante con aportes insuficientes de fósforo durante el período.

Introduction: The use of greater amounts of protein and energy during the first week of life is associated with hypophosphataemia in extreme preterm babies. The lowest phosphorus levels are described in intrauterine growth restricted (IUGR) babies. Objectives: To describe biochemistry levels in cord blood plasma in extreme premature, adequate and small for gestational age babies (AGA/SGA) and their relationship with plasma calcium and phosphorus levels during the first week of life. Patients and method: A descriptive clinical study was performed in the Neonatology Service at Hospital Dr. Sótero del Río during 2013 and 2014. A biochemical analysis of cord blood was performed on 43 premature babies, as well as plasma calcium and phosphorus levels during the first week. The adequacy for gestational age was obtained using Alarcón- Pittaluga growth curves. Statistical significance was P < .05. Results: Cholesterol, transaminases, albumin and creatinine levels were similar for both AGA and SGA babies. Levels of pH, phosphorus, calcium and alkaline phosphatase were significantly lower in SGA babies. Urea nitrogen, uric acid and triglycerides levels were higher in SGA. The analysis during the first week showed a strong reduction in phosphorus levels, as well as an increase in calcium levels in proportion to the decrease in phosphorus in the SGA sub- group. Conclusions: Intrauterine malnutrition in preterm babies is expressed in the modulation of plasma levels of calcium, phosphorus, alkaline phosphatase, urea nitrogen, uric acid and triglycerides. During post-natal life, when nutritional intake begins, a decrease in phosphorus and an increase in calcium levels appear, consistent with insufficient phosphorus intake during this period.

Hypophosphataemia among Severely-malnourished Children: Case Series.

Phosphorus is an essential substance in our body, and hypophosphataemia (HP) is well-described in rickets, refeeding syndrome, diabetic ketoacidosis (DKA), and in chronic alcohol-abuse. However, to our knowledge, HP among severely-malnourished children has not been studied in detail, and information on prevalence, severity, and treatment is scarce. Currently, there are only a few published case reports of HP. This case series describes three cases of HP that presented to Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Our first case required mechanical ventilation for respiratory distress associated with severe hypokalaemia (K 1.1 mmol/L) and moderate hypophosphataemia (P 2.1 mg/dL). The second case presented with severe sepsis which was associated with symptomatic hypocalcaemia (Ca 1.68 mmol/L), hypokalaemia (K 1.82 mmol/L), and severe hypophosphataemia (P 0.9 mg/dL). The third case presented with pneumonia and sepsis which were complicated by hypokalaemia (K 2.05 mmol/L) and severe hypophosphataemia (P 1.1 mg/dL). Marked lethargy and severe hypotonia were associated with HP in all of these cases. Manifestations of HP are diverse and can occur in association with other electrolyte imbalances, especially among malnourished children. Malnutrition, combined with sepsis, is one of the major killers of children younger than 5 years of age, and both malnutrition and sepsis can cause HP. It is concluded that the underlying causes of morbidity, including HP, should be actively sought and treated to reduce the mortality of children aged below five years.

Hypophosphataemic rickets/osteomalacia: A descriptive analysis.

Background & objectives: Hypophosphataemic rickets/osteomalacia (HRO) is an uncommon metabolic bone disorder which affects all ages and either sex. It is characterized by low concentration of serum phosphate levels leading to impairment of mineralization of bone matrix with variable aetiology. We present clinical profile and treatment outcome of 17 patients of HRO. Methods: Seventeen consecutive patients (8 were < 18 yr of age, with median age of presentation being 27.5 yr) of HRO who came to the department of Endocrinology in a tertiary care hospital in north India from January 2000 to December 2006 were included in the present study. Their aetiology, clinical features, biochemical parameters, radiographic features, treatment and outcome were analyzed. Results: HRO was commoner in females (70.5%) with positive family history observed in 6 (35.3%) patients. Common presenting features were short stature (58.8%), backache (58.8%), bony deformities (58.8%), joint pain (52.9%), fractures (29.4%) and dental abnormalities (23.5%). Radiological abnormalities noted were generalized bony deformities (58.8%), fractures (29.4%), and pseudo fractures (17.6%). Mesenchymal tumours were localized in the pelvis in one patient and in the right jaw in another. The patients were treated with calcium (elemental calcium 1 g/d) and oral phosphate supplements (dose 30 – 50mg/kg/day in divided doses) along with active vitamin D supplements (dose 1- 3 μg/day) and followed up for a mean of 2 yr. Two patients also received growth hormone (GH) therapy in the dose of 2U/day for 6 and 18 months respectively. Symptomatic well being was reported by all the patients and improvement was noted in the levels of phosphate (P<0.005) and alkaline phosphatase (P<0.05) after treatment. Interpretation & Conclusions: A diagnosis of HRO should be considered in all patients presenting with short stature, deformities or musculoskeletal pains along with low serum phosphate with normal iPTH and 25 – hydroxy vitamin D.