Treatment and Prevention of Liver Disease Associated with Parenteral Nutrition (PN)

Abstract

The present invention is based on the discovery that parenteral nutrition (PN) induced liver disease, e.g. fatty liver disease, can be prevented and even reversed by administration of primarily omega-3-fatty acid with PN rather than the administration of the standard intravenous lipid emulsions that contain primarily plant derived omega-6 fatty acid. Thus, the present invention provides a method for treating or preventing liver disease in a human patient obtaining nutritional support through PN. The method comprises intravenous administration of an effective amount of an omega-3-fatty acid emulsion to the patient, wherein the patient is not administered phytosterols or plant derived fatty acids, e.g. omega-6 fatty acids derived from a plant source, and wherein the administration of the omega-3-fatty acid emulsion to the patient is for a period greater than three weeks. Preferably, the administration is for a period of greater than six weeks. More preferably, the administration is for a period greater than three months.

We claim: 
     
         1 . A method for treating or preventing liver disease in a human patient obtaining nutritional support through parenteral nutrition (PN) comprising intravenous administration of an effective amount of an omega-3-fatty acid emulsion to the patient, wherein the patient is not administered phytosterols or plant derived fatty acids, and wherein the administration of the omega-3-fatty acid emulsion to the patient is for a period greater than three weeks. 
     
     
         2 . The method of  claim 1 , wherein the administration of the omega-3-fatty acid emulsion to the patient is for a period greater than 6 weeks. 
     
     
         3 . The method of  claim 1 , wherein the administration of the omega-3-fatty acid emulsion to the patient is for a period greater than 3 months. 
     
     
         4 . The method of  claim 1 , wherein the liver disease is fatty liver disease. 
     
     
         5 . The method of  claim 1 , wherein the omega-3-fatty acid emulsion comprises fish oil. 
     
     
         6 . The method of  claim 5 , wherein the fish oil is derived from a source selected from the group consisting of menhaden, herring, mackerel, cod, caplin, tilapia, tuna, sardine, pacific saury, salmon, arctic char and krill. 
     
     
         7 . The method of  claim 5 , wherein the fatty acid emulsion is Omegaven. 
     
     
         8 . The method of  claim 1 , wherein the omega-3-fatty acid emulsion is prepared using an emulsifying agent selected from the group consisting of egg phosphatidylcholine, egg lecithin, L-α-dipalmitoyl phosphatidylcholine (DPPC), DL-α-dipalmitoyl phosphatidylethanolamine (DPPE), and dioleoyl phosphatidylcholine (DOPC). 
     
     
         9 . The method of  claim 1 , wherein the patient is a newborn. 
     
     
         10 . The method of  claim 1 , wherein the patient is a premature newborn. 
     
     
         11 . The method of  claim 1 , wherein the patient is a an infant. 
     
     
         12 . The method of  claim 1 , wherein the patient is a child under the age of 18. 
     
     
         13 . The method of  claim 1 , wherein the patient is a child under the age of 12. 
     
     
         14 . The method of  claim 1 , wherein the patient is an adult receiving long term nutritional support through PN. 
     
     
         15 . The method of  claim 1 , wherein the omega-3-fatty acid emulsion is administered until said patient is capable of receiving adequate nutrition from enteral food intake. 
     
     
         16 . The method of  claim 1 , wherein the omega-3-fatty acid is administered at a dose of 0.2 g/kg/day to 3.0 g/kg/day. 
     
     
         17 . The method of  claim 1 , wherein the omega-3-fatty acid is administered at a dose of 0.5 g/kg/day to 1.0 g/kg/day. 
     
     
         18 . A method for treating or preventing liver disease in a newborn, premature newborn, or infant patient that is obtaining nutritional support through parenteral nutrition (PN) comprising intravenous administration of an effective amount of an omega-3-fatty acid emulsion to the patient, wherein the patient is not administered phytosterols or plant derived fatty acids, and wherein the administration of the omega-3-fatty acid emulsion to the patient is for a period greater than three weeks. 
     
     
         19 . The use of an omega-3-fatty acid emulsion for treating or preventing liver disease in a newborn, premature newborn, or infant patient that is obtaining nutritional support through parenteral nutrition (PN), wherein an effective amount of an omega-3-fatty acid emulsion is administered to the newborn, premature newborn, or infant patient by intravenous administration under conditions where the patient is not administered phytosterols or plant derived fatty acids, and wherein the administration of the omega-3-fatty acid emulsion to the patient is for a period greater than three weeks.