Liver disease with parenteral nutrition

Progression of liver disease during parenteral nutrition in two infants with intestinal failure was rapidly exacerbated by ischemic liver damage [67 ]. 

A fish oil-based intravenous lipid emulsion in the treatment of liver disease associated with parenteral nutrition has been compared with soybean oil in an open study in 42 infants with short bowel syndrome who developed cholestasis [35 ]. There were three deaths and one liver transplantation in those who received the fish oil, compared with 12 deaths and 6 transplants in those who received soybean oil The fish oil was not associated with hypertriglyceridemia, coagulopathy, or deficiency of essential fatty acids. 

Le HD, de Meijer VE, Zurakowski D, Meisel JA, Gura KM, Puder M. Parenteral fish oil as monotherapy improves lipid profiles in children with parenteral nutrition-associated liver disease. JPEN J Parenter Enteral Nutr 2010 34(5) 477-84. 

L.G., an 18 year old with granulomatous ileocolitis treated for 14 days with parenteral nutrition had a percutaneous menghini needle liver biopsy after clinical and chemical abnormalities suggested early hepatic disease. Fig. 2 represents a high power view of the biopsy specimen showing evidence of a focal round cell infiltrate with mild to moderate steatosis. 

Santra S, McKiernan P, Lander A, Dalzell AM, Baillie C, Beath S, Gupte GL. Ischemic hepatitis is a risk factor for progression of liver disease associated with parenteral nutrition in intestinal failure. J Pediatr Gastroenterol Nutr 2008 47(3) 367-9. 

Linoleic acid and alpha-linoleic acid are essential fatty acids that are provided in any long-term parenteral nutrition by administering fat emulsions at least twice a week. Fatty acid deficiency is a common complication of severe end-stage liver disease. The ability of short-term intravenous lipid supplementation to reverse fatty acid deficiencies has been studied in patients with chronic liver disease and low plasma concentrations of fatty acids (914). Shortterm supplementation failed to normalize triglycerides. 

When oral intake is precluded, the recommended daily parenteral supplementation of manganese is 0.15-0.8 mg. Manganese is mainly excreted in the bile during cholestasis serum manganese levels may rise, and manganese toxicity can result. Hjq)ermanganesemia after parenteral nutrition when first reported was linked to portosystemic encephalopathy. Patients with liver disease were particularly at risk. 

Intestinal transplantation is combined with liver transplantation in 46% of cases, because of terminal liver failure (93). Of 78 patients who had received parenteral nutrition for more than 2 years n — 66) and/ or had short bowel syndrome and could not be weaned from parenteral nutrition (n = 12), 58 developed chronic cholestasis and 37 developed one or more severe liver complication (serum bilirubin concentration 60 pmol/l, factor V (proaccelerin) 50%, portal hypertension, encephalopathy, ascites, bleeding from the gastrointestinal tract, or histological findings consisting of extensive fibrosis and cirrhosis) after 6 (3-132) months and 17 (2-155) months respectively. Liver disease was responsible for deaths in 6.5% of the patients (22% of deaths). 

In a prospective prevalence study of liver disease in 90 patients with permanent intestinal failure receiving parenteral nutrition hver biopsy was performed in 57 (95). Chronic cholestasis developed in 58 patients after a median of 6 (range 3-132) months, and 37 developed comphcated liver disease after a median of 17 (range 2-155) months. Chronic cholestasis was significantly associated with a risk of liver disease independent of parenteral nutrition, a bowel remnant shorter than 50 cm, and a lipid intake of 1 g/kg/day or more hver disease related to parenteral nutrition was significantly associated with chronic cholestasis and a parenteral hpid intake of 1 g/kg/day or more. The authors concluded that the prevalence of hver disease increased with the duration of parenteral nutrition and was one of the main causes of death in patients with permanent intestinal failure. Parenteral intake of long-chain hpid emulsion should be restricted to less than 1 g/kg/day. 

Two infants with intestinal failure and parenteral nutrition-associated liver disease were given an intravenous fat emulsion containing primarily omega-3 fatty acids instead of the conventional emulsion [30 ]. Biochemical tests of liver function improved significantly. One child was removed from the liver transplantation list because of improved hepatic function, and the second child had complete resolution of cholestasis while solely on parenteral nutrition. 

In contrast, in a retrospective analysis of 292 neonates who received parenteral nutrition with lipid emulsions containing omega-3 fatty acids for more than 1 day, 104 (36%) developed cholestasis after a mean of 22 days, with a conjugated bilirubin concentration over 34 pmol/l 31 had a serum conjugated bilirubin concentration over 100 pmoUl and 13 developed liver failure 4 underwent transplantation and 5 died of hepatic disease [385]. The authors suggested that in the absence of definitive evidence of efficacy, as well as increased costs, it is difficult to justify the routine use of lipid... 

Since one could not exclude the possibility that the findings in this teenager were not related to the mild focal abnormalities often seen in granulomatous ileocolitis, two subsequent patients (M.P. and I.W.) with this latter disease and in whom this treatment modality appeared indicated were subjected to a percutaneous liver biopsy prior to the initiation of parenteral nutrition. In both instances abnormal hepatic parenchyma was appreciated. Fig. 3a demonstrates the focal inflammatory cell response in M.P. Repeat biopsies of both patients after several weeks of parenteral nutrition revealed a more severe degree of these same findings. (Fig. 3b). 

In a prospective cohort study including 24 infants, the incidence and risk factors of parenteral nutrition-associated liver disease (PNALD) was determined. Eight infants developed PNALD. The concluded that the duration of enteral starvation, gastrointestinal surgery, duration of enteral nutrition, maximum caloric and carbohydrate intakes were significant risks of PNALD in newborn infants [lob ll. In a retrospective review of the safety and efficacy of PN among 105 paediatric patients with bum injuries (>30% total-body sxuface area), no respiratory or blood infections were observed with the use of parenteral nutrition, and the overall mortality rate was 4% [107 ]. 

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