Phytosterolemia in parenteral nutrition patients: implications for liver disease development.

OBJECTIVE: Phytosterols present in parenteral nutrition (PN) lipid emulsions have been linked to phytosterolemia and cholestatic liver disease, although no direct relation has been established. We investigated the relation among plasma phytosterol (PY) infused, total plasma PY levels, and possible links to PN-associated liver disease. METHODS: Twenty-seven adult patients on home PN were enrolled in the study. PYs were measured in plasma and lipid emulsions by gas chromatography. Liver function tests and blood counts were assessed to identify hepatic impairment, and biopsies were performed in eight patients. RESULTS: Mean total plasma PY level was higher in patients than in controls (55.4 +/- 6.2 versus 14.8 +/- 2.3 microg/mL). Simple linear regression models showed a correlation among total plasma PY, liver function tests, and platelet counts, which was stronger for total bilirubin (r(2) = 0.53, P = 0.0001) and aspartate aminotransferase (r(2) = 0.50, P = 0.0001) and weaker for platelet counts (r(2) = 0.158, P = 0.04); between infused lipid and liver function tests, the correlation was significant for total bilirubin (r(2) = 0.19, P = 0.038) and aspartate aminotransferase (r(2) = 0.164, P = 0.049). In multiple linear regression analysis, a decreased oral diet (b = -52.3, P = 0.001) and infused PY (b = 2.54, P = 0.093) were risk factors for high plasma PY levels (r(2) = 0.54). Biopsies showed moderate to severe liver impairment in five patients. CONCLUSION: Liver damage may be linked to high plasma PY levels and strengthened by lack of an oral diet in patients on home PN.

Apo AIV and Citrulline Plasma Concentrations in Short Bowel Syndrome Patients: The Influence of Short Bowel Anatomy.

INTRODUCTION: Parenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients is linked to the functionality of the remnant small bowel (RSB). Patients may wean off PN following a period of intestinal adaptation that restores this functionality. Currently, plasma citrulline is the standard biomarker for monitoring intestinal functionality and adaptation. However, available studies reveal that the relationship the biomarker with the length and function of the RSB is arguable. Thus, having additional biomarkers would improve pointing out PN weaning. AIM: By measuring concomitant changes in citrulline and the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account the anatomy of the RSB, this exploratory study aims to a better understanding of the intestinal adaptation process and characterization of the SBS patients under PN. METHODS: Thirty four adult SBS patients were selected and assigned to adapted (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining jejunum and ileum lengths were recorded. The aSBS patients were either on an oral diet (ORAL group), those with intestinal insufficiency, or on oral and home parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV and citrulline were analyzed in plasma samples after overnight fasting. An exploratory ROC analysis using citrulline as gold standard was performed. RESULTS: Biomarkers, Apo AIV and citrulline showed a significant correlation with RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with RSBL (rb = 0.54) and with ileum length (rb = 0.84). In patients without ileum neither biomarker showed any correlation with RSBL. ROC analysis indicated the Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS HPN and ORAL groups. CONCLUSIONS: Therefore, in addition to citrulline, Apo AIV can be set as a biomarker to monitor intestinal adaptation in SBS patients. As short bowel anatomy is shown to influence citrulline and Apo AIV plasma values, both biomarkers complement each other furnishing a new insight to manage PN dependence.

Orotic aciduria and plasma urea cycle-related amino acid alterations in short bowel syndrome, evoked by an arginine-free diet.

BACKGROUND: The small bowel is believed to play a crucial role in endogenous arginine synthesis. Therefore, an insufficient arginine supply in the situation of massive intestinal resection might impede normal arginine metabolism. This study sought to determine the clinical and metabolic effects of an arginine-free diet in stable short-bowel patients. METHODS: Four patients, mean age 49 years (range: 26-67), mean time from intestinal resection 46 m (range: 15-97), and remnant small bowel of 30 to 100 cm consumed an L-amino acid arginine-free diet (egg pattern) for 5 days (0.9 g protein equivalent/kg/d plus malabsorption adjustments). Fasting plasma amino acids, ammonium, and blood chemistries were assessed at days 0, 3, and 5. Urinary orotate, orotidine, uric acid, urea, creatinine, and total nitrogen were evaluated daily. RESULTS: Significant decreases in plasma levels of arginine, ornithine, and hydroxyproline occurred at day 5. A decreasing trend in plasma citrulline and a significant plasma glutamine increase were also observed in the same period. Conversely, ammonium concentrations remained normal. Regarding urine compounds, striking orotic aciduria with a peak at day 4 (14-fold vs baseline) and significant decreases in uric acid and urea excretion were found. There were no relevant clinical events. CONCLUSIONS: Despite the limited number of patients in our work and their relative heterogeneity, our results support the idea of the indispensability of an exogenous arginine supply in humans under short bowel syndrome conditions. Studies in larger series are needed to further investigate these findings.