Can Fish Oil-based Parenteral Nutrition Improve Cholestasis?
Can Fish Oil-based Parenteral Nutrition Improve Cholestasis?
A 43-year-old man presented as an emergency with acute, severe abdominal pain. He had a significant history of vascular disease, having had mesenteric and iliac artery stenting in the past. Laparotomy showed necrosis of the small bowel from the duodenojejunal flexure to the distal terminal ileum consistent with mesenteric infarction. A small-bowel resection was performed and he was left with a duodenostomy with most of his colon intact but not in continuity. He was discharged home from another hospital after 4 weeks with home PN, tolerating only small volumes of oral fluids. On discharge his weight was 56 kg and body mass index (BMI) 18.3. His PN regimen provided 11.55 g/day nitrogen, 800 kcal/day lipid and 800 kcal/day carbohydrate with appropriate electrolytes, vitamins (Cernevit, Baxter Healthcare, Newbury, UK) and trace elements (Decan, Baxter Healthcare UK). The lipid emulsion was ClinOleic 20% (Baxter Healthcare, UK), a mixture of refined olive oil (80%) and soybean oil (20%).
Six months later he became jaundiced with cholestatic liver blood tests and his weight had fallen to 43 kg (BMI 14.5). Serological tests for viral hepatitis and autoimmune liver disease were negative. Endoscopic retrograde pancreaticocholangiography to rule out biliary obstruction was normal. As other potential causes of liver dysfunction were excluded, a liver biopsy was performed. The parenchyma showed severe acute cholestasis (bile stasis) (figure 1) and minimal steatosis without steatohepatitis. The portal tracts showed marked bile ductular proliferation and inflammation. Copper-associated protein was present in periportal hepatocytes, indicating chronic cholestasis. There was moderate portal fibrosis, again indicating chronic disease. These features were all entirely consistent with PNALD.
(Enlarge Image)
Figure 1.
Liver biopsy specimen. Severe acute cholestasis (bile stasis) in the parenchyma. Plugs of brown bile are seen both in hepatocytes, in their canaliculi which are dilated, and in macrophages.
Despite a reduction in the lipid content of the PN and a trial of N-acetylcysteine supplementation there was no improvement in his liver function. He developed portal hypertension and bled from a gastric varix, requiring endoscopic haemostasis. It was felt unwise to attempt to re-anastomose his blood because the remaining blood supply was through tenuous collaterals and could not be improved by angioplasty or stenting. He was referred for consideration of a small-bowel and liver transplant.
Four months later, in light of his deteriorating liver function the feed was changed from 500 ml once weekly of ClinOleic 20% to SMOFlipid 20% (Fresenius Kabi Runcorn, UK), a mixture of soybean (30%), medium-chain triglycerides (30%), olive oil (25%) and fish oils (15%). At the same time he developed a stoma stenosis, which was revised allowing him to increase his oral fluids. Eight weeks later the patient returned to the clinic and was clinically less jaundiced with improvement in the liver function tests. There was a gradual normalisation of his serum bilirubin, transaminases and alkaline phosphatase levels (figure 2). His albumin rose from a nadir of 12 g/l to 37 g/l. A repeat upper gastrointestinal endoscopy showed resolution of the gastric varices. Over the course of his PN he had serial fibroscan assessments. These showed a progressive fall in liver stiffness after the introduction of SMOFlipid. Before changing to SMOFlipid the liver stiffness was 16.0 (IQR 3.1). Four months and 1 year after starting SMOFlipid the liver stiffness was 10.3 (IQR 2.6) and 8.8 (IQR 0.7), respectively.
(Enlarge Image)
Figure 2.
Change in liver blood tests after introduction of SMOFlipid. AST, aspartate aminotransferase.
After lengthy consideration, he underwent a multivisceral transplant of stomach, liver, duodenum and pancreas in Cambridge. He was discharged 12 weeks postoperatively and, to date, shows no sign of transplant rejection. His nutrition is currently managed by naso-jejunal feeding with a current regimen of 1 litre of Nepro (Abbott Nutrition, Maidenhead, USA) and 2500 ml clear fluid a day.
He continues to receive regular input from general surgery, gastroenterology and hepatology services but remains well with occasional short-term admissions to assess renal function (latest urea: 7.3 mmol/l, creatinine: 126 μmol/l) and nutritional status. His most recent BMI was recorded as 18.6, a significant improvement from a low of 14.9.
Case Report
A 43-year-old man presented as an emergency with acute, severe abdominal pain. He had a significant history of vascular disease, having had mesenteric and iliac artery stenting in the past. Laparotomy showed necrosis of the small bowel from the duodenojejunal flexure to the distal terminal ileum consistent with mesenteric infarction. A small-bowel resection was performed and he was left with a duodenostomy with most of his colon intact but not in continuity. He was discharged home from another hospital after 4 weeks with home PN, tolerating only small volumes of oral fluids. On discharge his weight was 56 kg and body mass index (BMI) 18.3. His PN regimen provided 11.55 g/day nitrogen, 800 kcal/day lipid and 800 kcal/day carbohydrate with appropriate electrolytes, vitamins (Cernevit, Baxter Healthcare, Newbury, UK) and trace elements (Decan, Baxter Healthcare UK). The lipid emulsion was ClinOleic 20% (Baxter Healthcare, UK), a mixture of refined olive oil (80%) and soybean oil (20%).
Six months later he became jaundiced with cholestatic liver blood tests and his weight had fallen to 43 kg (BMI 14.5). Serological tests for viral hepatitis and autoimmune liver disease were negative. Endoscopic retrograde pancreaticocholangiography to rule out biliary obstruction was normal. As other potential causes of liver dysfunction were excluded, a liver biopsy was performed. The parenchyma showed severe acute cholestasis (bile stasis) (figure 1) and minimal steatosis without steatohepatitis. The portal tracts showed marked bile ductular proliferation and inflammation. Copper-associated protein was present in periportal hepatocytes, indicating chronic cholestasis. There was moderate portal fibrosis, again indicating chronic disease. These features were all entirely consistent with PNALD.
(Enlarge Image)
Figure 1.
Liver biopsy specimen. Severe acute cholestasis (bile stasis) in the parenchyma. Plugs of brown bile are seen both in hepatocytes, in their canaliculi which are dilated, and in macrophages.
Despite a reduction in the lipid content of the PN and a trial of N-acetylcysteine supplementation there was no improvement in his liver function. He developed portal hypertension and bled from a gastric varix, requiring endoscopic haemostasis. It was felt unwise to attempt to re-anastomose his blood because the remaining blood supply was through tenuous collaterals and could not be improved by angioplasty or stenting. He was referred for consideration of a small-bowel and liver transplant.
Treatment
Four months later, in light of his deteriorating liver function the feed was changed from 500 ml once weekly of ClinOleic 20% to SMOFlipid 20% (Fresenius Kabi Runcorn, UK), a mixture of soybean (30%), medium-chain triglycerides (30%), olive oil (25%) and fish oils (15%). At the same time he developed a stoma stenosis, which was revised allowing him to increase his oral fluids. Eight weeks later the patient returned to the clinic and was clinically less jaundiced with improvement in the liver function tests. There was a gradual normalisation of his serum bilirubin, transaminases and alkaline phosphatase levels (figure 2). His albumin rose from a nadir of 12 g/l to 37 g/l. A repeat upper gastrointestinal endoscopy showed resolution of the gastric varices. Over the course of his PN he had serial fibroscan assessments. These showed a progressive fall in liver stiffness after the introduction of SMOFlipid. Before changing to SMOFlipid the liver stiffness was 16.0 (IQR 3.1). Four months and 1 year after starting SMOFlipid the liver stiffness was 10.3 (IQR 2.6) and 8.8 (IQR 0.7), respectively.
(Enlarge Image)
Figure 2.
Change in liver blood tests after introduction of SMOFlipid. AST, aspartate aminotransferase.
Outcome and Follow-up
After lengthy consideration, he underwent a multivisceral transplant of stomach, liver, duodenum and pancreas in Cambridge. He was discharged 12 weeks postoperatively and, to date, shows no sign of transplant rejection. His nutrition is currently managed by naso-jejunal feeding with a current regimen of 1 litre of Nepro (Abbott Nutrition, Maidenhead, USA) and 2500 ml clear fluid a day.
He continues to receive regular input from general surgery, gastroenterology and hepatology services but remains well with occasional short-term admissions to assess renal function (latest urea: 7.3 mmol/l, creatinine: 126 μmol/l) and nutritional status. His most recent BMI was recorded as 18.6, a significant improvement from a low of 14.9.
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