Frank H. Anderson

Sensitivity and Specificity of Liver Function Tests in the Detection of Parenteral Nutrition-Associated Cholestasis

We carried out a study to determine which of the liver function tests was the most sensitive and/or specific in detecting parenteral nutrition associated cholestasis. The tests utilized were alkaline phosphatase, gamma-glutamyl transpeptidase, cholylglycine, sulfolithocholylglycine, and bilirubin. Fifty-nine patients with no prior evidence of liver dysfunction were studied. We found gamma-glutamyl transpeptidase to be the most sensitive (89.5%) and also the least specific (61.9% specificity). Specificity of gamma-glutamyl transpeptidase was improved when it was combined with alkaline phosphatase. We recommend the combination of these two enzymes as the most cost effective way of detecting parenteral nutrition-associated cholestasis.

Extracorporeal photopheresis (ECP) in patients with steroid-dependent Crohn's disease: An open-label, multicenter, prospective trial

Background:Extracorporeal photopheresis (ECP) involves ex vivo leukocyte treatment with methoxsalen and UVA light to generate a tolerogenic response. A previous trial demonstrated that ECP permits corticosteroid withdrawal in steroid-dependent Crohns disease (CD) patients who were in clinical remission. We studied the effect of ECP on steroid withdrawal in steroid-dependent CD. Methods:Patients with CD for ≥6 months, in remission at baseline while on steroids, but who had failed at ≥1 steroid withdrawal were included. Patients received two ECP treatments every 2 weeks for the 24-week steroid tapering period and underwent steroid-tapering. Patients completing steroid tapering could receive maintenance ECP (two treatments/week) every month for 24 weeks. Results:Thirty-one patients (Crohns Disease Activity Index [CDAI] score 91; Inflammatory Bowel Disease Questionnaire [IBDQ] 172.5) were enrolled (baseline corticosteroid dose, 20 mg/day); 65% were refractory to/intolerant of anti-tumor necrosis factor (TNF) agents or immunosup-pressants. After 24 weeks of ECP, 7 of 31 (22.6%) patients discontinued steroids while maintaining a CDAI of <150. At week 24, the steroid dose for the remaining patients on corticosteroids was 10 mg (P < 0.003 vs. baseline) with a CDAI of 110 and an IBDQ of 179. Following maintenance treatment, three patients remained in steroid-free remission. The 10 patients in the study and receiving ECP at week 48 had a steroid dose of 3.5 mg with a CDAI of 40 and an IBDQ of 188. Conclusions:ECP permitted discontinuation or reduction of steroids in a population of refractory steroid-dependent CD patients. ECP may be useful in permitting steroid withdrawal in selected steroid-dependent CD patients. Ideally, these results need to be confirmed in a “sham-controlled” clinical trial.

Acute liver failure: a possible consequence of severe hypophosphatemia

A patient with acute liver failure, in whom no infectious, toxic, or other cause of hepatic damage could be found, developed severe hypophosphatemia along with hepatocellular necrosis. We propose that phosphate depletion may be responsible for the liver cell damage, as hypophosphatemia impairs tissue oxygenation and depletes cellular ATP.

Relationship between Serum Albumin and Parenteral Nutrition-Associated Cholestasis

In a prospective study of 59 patients receiving total parenteral nutrition we found that patients with low serum albumin were more likely to develop cholestasis than patients with normal serum albumin. Only 25% of patients with a normal serum albumin developed cholestasis. Seventy-nine percent of patients with low serum albumin (less than 3.5 g/dl) developed cholestasis (p less than 0.01). In those patients who developed cholestasis, there was a significant correlation (r = 0.63, p less than 0.01) between the serum albumin and the number of days after onset of total parenteral nutrition when cholestasis appeared. The role of hypoalbuminemia in the development of total parenteral nutrition-associated cholestasis deserves further study.