Persistent inflammation and immune activation contribute to cholestasis in patients receiving home parenteral nutrition

Abstract 

Liver disease is frequent in patients taking home parenteral nutrition (HPN), but its cause remains unclear. Ongoing inflammation was implicated in HPN-associated cholestasis, so we examined the relation between liver-enzyme concentrations and circulating inflammatory and immune markers in these patients. In 17 HPN patients and 10 age- and sex-matched control subjects, we examined erythrocyte sedimentation rate, blood neopterin, soluble interleukin (IL)–2 receptors, circulating tumor necrosis factor-α, IL-6, aspartate and alanine aminotransferases, alkaline phosphatases, and γ-glutamyltranspeptidase (GGT) concentrations. Fourteen of 17 patients had abnormal liver function tests with an increase in alkaline phosphatases (P < 0.001), γ-glutamyltranspeptidase (P < 0.01), and aspartate aminotransferase (P < 0.01). Alkaline phosphatases were positively correlated to erythrocyte sedimentation rate, neopterin, tumor necrosis factor-α, and IL-6. γ-Glutamyltranspeptidase was positively linked to tumor necrosis factor-α and soluble IL-2 receptors. There was no link between aminotransferases and inflammatory parameters. Liver-enzyme concentrations were correlated to the amount of total intravenous calories and calories originating from carbohydrates but not to infused lipids (median infused lipids · kg⁻¹ body weight · d⁻¹ = 0.62 g) in contrast to recently published data. Our results confirmed that the number of infused calories contributes to liver toxicity in HPN patients and strongly suggested that sustained inflammation is probably a key factor in worsening HPN-associated cholestasis.

Keywords:  home parenteral nutrition, cholestasis, inflammation, bacterial translocation, intravenous nutrient toxicity