What is the risk of liver injury with Total Parenteral Nutrition (TPN)?

Risk of Liver Injury with Total Parenteral Nutrition (TPN)

TPN therapy can cause significant liver injury in up to 50% of patients receiving long-term treatment, with risk increasing with duration of therapy and potentially progressing to severe liver disease including fibrosis and cirrhosis in some patients. 1

Types and Prevalence of TPN-Related Liver Injury

• Mild increases in alkaline phosphatase indicating cholestasis occur in approximately 50% of patients on home parenteral nutrition (HPN), often accompanied by modest increases in transaminase levels and small increases in conjugated bilirubin 1
• Liver abnormalities in TPN patients may progress to severe histological changes with portal fibrosis and/or cirrhosis, which can result in liver failure and death in the long term (months to years) 1
• In adults, steatosis (fatty liver) is the most common initial manifestation, while infants and neonates are more susceptible to hepatocellular injury or cholestasis 1
• The incidence of advanced intestinal failure-associated liver disease (IFALD)/parenteral nutrition-associated liver disease (PNALD) in adults ranges from 0% to 50%, with mortality ranging from 0% to 22% 1

Risk Factors for TPN-Related Liver Injury

Patient-Related Factors:

• Short bowel syndrome with less than 150 cm of remnant bowel is positively related to the development of chronic cholestasis during HPN 1
• Infants and neonates are at higher risk, with PNAC occurring in up to 60% of infants and up to 85% of neonates who require long-term PN for intestinal failure 1
• Patients with extensive small bowel resection are at increased risk of liver complications 1

TPN Formulation-Related Factors:

• Intravenous lipid (particularly 20% soya emulsions rich in n-6 PUFA) chronically given at more than 1 g/kg per day is strongly associated with both chronic cholestasis and severe liver disease in patients on HPN 1
• The risk of severe liver disease after 2 years of HPN was 50% in patients receiving more than 1 g/kg per day of soya lipids daily compared to only 20% in those receiving less than 1 g/kg per day 1
• Overfeeding, particularly with glucose and lipids, increases the risk of liver injury 1
• Continuous (versus cyclic) HPN administration is considered a risk factor 1

Administration-Related Factors:

• Duration of TPN is a significant risk factor - longer duration correlates with increased risk and severity of liver injury 1
• Line sepsis and infections increase the risk of liver complications 1

Prevention Strategies

Optimize TPN Composition:

• The fat/glucose energy ratio should not exceed 40:60 and lipids should comprise no more than 1 g/kg per day 1
• Avoid all forms of overfeeding 1
• Limit glucose administration to less than 7 mg/kg per minute 1
• In adults with suspected PNALD, consider using lipid emulsions with a reduced n6/n3 ratio 1
• In infants and children with PNAC, lipid emulsions enriched with omega-3-fatty acids can be used 1

Administration Strategies:

• Use cyclic rather than continuous TPN when possible 1
• Implement enteral stimulation whenever possible, even minimal amounts may help prevent metabolic complications 1
• Promptly control infections, particularly line sepsis, to help prevent deterioration of liver abnormalities 1

Monitoring:

• Monitor liver function tests regularly in patients receiving TPN 1
• Monitor plasma or whole blood concentrations of manganese and copper in long-term TPN patients, as impaired liver excretory function may lead to accumulation of these elements 1
• Consider liver imaging to confirm intrahepatic cholestasis when liver enzyme abnormalities develop 1

Management of TPN-Related Liver Injury

• PN should be used in cirrhotic patients only when oral and/or enteral nutrition (EN) are ineffective or not feasible 1
• In patients with liver disease, care should be taken to avoid infections of the intravenous lines as these patients are more prone to infection and sepsis 1
• In patients with compensated liver cirrhosis, standard amino acid solutions can be used 1
• For patients with overt hepatic encephalopathy, specific "hepatic formula" amino acid solutions high in branched-chain amino acids (BCAA, 35-45%) but low in tryptophan, aromatic and sulfur-containing amino acids may be considered 1
• Supplementation with taurine in parenteral nutrition has been reported to ameliorate PN-associated cholestasis, though reliable studies are limited 1

Clinical Implications

• TPN-related liver injury can range from mild, reversible abnormalities to progressive liver disease leading to liver failure 1
• Clinical markers of liver injury (e.g., elevated liver enzymes) do not always predict the degree of hepatocellular injury or fibrosis 1
• In severe cases, TPN-related liver disease can become an indication for liver transplantation, particularly in pediatric patients 1
• The pathogenesis of TPN-related liver disease is multifactorial, making it difficult to differentiate between the role of the underlying condition (e.g., extensive small bowel resection, sepsis) and that of PN itself in adults 1