The regenerating liver after partial hepatectomy is one of the few physiologic models of cellular proliferation in the adult animal. During hepatic regeneration, the animal is able to maintain metabolic homeostasis despite the acute loss of two thirds of hepatic tissue. In examining the molecular mechanisms regulating hepatic regeneration, we isolated novel immediate-early genes that are rapidly induced as the remnant liver undergoes the transition from its normal quiescent state into the G1 phase of the cell cycle. One of the most rapidly and highly induced genes which we initially termed RL-1, encodes rat glucose-6-phosphatase (rG6Pase). G6Pase mRNA peaks at 30 min and 36-48 h after hepatectomy correlating with the first and second rounds of cell division. This finding is compatible with studies that showed that G6Pase enzyme activity increases during liver regeneration. However, the increase in G6Pase mRNA is much more dramatic, indicating that it is a more sensitive indicator of this regulation. G6Pase gene expression peaks in the perinatal time period in the liver and remains elevated during the first month of life. The expression of the G6Pase gene is also dramatically elevated in BB diabetic rats, again higher than the enzyme elevation, and its relative induction after partial hepatectomy is blunted in these animals. Insulin treatment of partially hepatectomized diabetic animals downregulates the expression of G6Pase mRNA. Using specific antibodies against G6Pase, we detect a 36-kD G6Pase protein, and its level is elevated in regenerating and diabetic livers. The pattern of G6Pase mRNA expression appears to reflect similar changes in insulin and glucagon levels which accompany diabetes and hepatic proliferation. The elevation of G6Pase expression in these conditions is indicative of its importance as a regulator of glucose homeostasis in normal and abnormal physiologic states. (J. Clin. Invest. 1995. 95:832-841.)
To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.
Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study.
The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages less than 1, 1-5 and greater than 5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight less than -1 was 57%, greater than -1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 +/- 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.
The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 +/- 0.2) and stunted (mean s.d. height = -2.2 +/- 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium--mean % expected for age = 58 +/- 5%, n = 15). Mean ad libitum nutrient intake was 63 +/- 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight greater than -1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight less than -1.0) was 38% (P less than 0.003). Declining nutritional status during the waiting period also adversely affected outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Pre-operative nutritional support was studied in 28 children with end-stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi-elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120-150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58-100% RDI. A significant improvement in mean Z-score for body weight (denoting catch-up) was noted only in those children who received nasogastric supplements enriched with branched-chain amino acids. The standard enterally-fed group maintained their body weight and Z-scores did not change significantly. In contrast, body weight Z-scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end-stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branched-chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.
Incidence rates of paediatric IBD in New Zealand are comparable to the highest rates published in the literature from Western Europe and North America. Ongoing prospective ascertainment of the incidence of paediatric IBD is required to better understand the environmental factors, which are accounting for this increase in disease burden.
The point prevalence of pediatric IBD in New Zealand represents the first-ever national, population-based prevalence rates of pediatric IBD published. Results from the Paediatric IBD in New Zealand (PINZ) study are also the first to show markedly higher prevalence rates of IBD in the southern part of a country compared with its northern counterpart. Ongoing prospective ascertainment of the incidence of pediatric IBD is required.
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