The liver damage associated with TPN may be reversible; however, in situations in which prolonged TPN is required, cirrhosis and eventually liver failure have occurred. In fact, end-stage liver disease has replaced catheter-related sepsis and malnutrition as the leading cause of death in TPN-dependent infants with short bowel syndrome.
Infants, particularly those born preterm, are most susceptible to hepatic injury from TPN.
The most common feature of this injury is TPN-associated cholestasis, which is generally accepted to be related to multiple factors. Premature infants will often rely solely on parenteral nutrition for long periods of time because of bowel immaturity. Necrotizing enterocolitis or congenital malformations of the gut with or without surgical resection often make prolonged use of TPN a necessity. Younger gestational age, lower birth weight, and a longer duration of TPN are associated with increased likelihood of TPN-associated cholestasis. Comorbid conditions
such as sepsis, hypoxia, or immature hepatic function are commonly encountered in the preterm infant, but TPN-related factors such as taurine or carnitine deficiency may also play important roles in the development of cholestasis and subsequent hepatic disease.
The onset of TPN-associated cholestasis (TPN-AC) is usually insidious. Hepatomegaly and conjugated hyperbilirubinemia raise the suspicion of likely TPN-associated cholestasis, but other etiologies of cholestasis must be considered . Because TPN-AC is often a diagnosis of exclusion, the evaluation includes ultrasonography and possibly hepatobiliary scintigraphy, which may identify an obstructive lesion. Other considerations are inborn errors of metabolism and congenital infection. A liver biopsy may help to exclude disorders such as storage diseases; however, the histopathology seen with TPN-associated cholestasis includes portal inflammation, cholestasis, and frequently fibrosis, which are suggestive but not diagnostic findings.
Because the specific cause of liver disease associated with TPN has not been determined, the treatment remains ill defined. Provision of at least some enteral nutrition has been shown to improve cholestasis and slow the development of liver injury. Agents such as phenobarbital and ursodeoxycholic acid are frequently used to improve bile flow. Other treatment modalities involve preventing photooxidation of the TPN solution, cycling the parenteral nutrition, and modifying its composition. In its early stages, TPN-associated liver disease may be reversible if enteral nutrition can be instituted.
In older children, adolescents, and adults, TPN-associated liver injury is more likely to present with steatosis (fatty liver) than cholestasis and inflammation. The pathophysiological process responsible for the steatosis is not completely understood, but possible mechanisms include an excessive calorie-to-nitrogen ratio, an excessive glucose infusion rate, and carnitine deficiency. As with cholestatic liver injury in infants, cessation of TPN usually results in a normalization of liver enzymes.
The most common feature of this injury is TPN-associated cholestasis, which is generally accepted to be related to multiple factors. Premature infants will often rely solely on parenteral nutrition for long periods of time because of bowel immaturity. Necrotizing enterocolitis or congenital malformations of the gut with or without surgical resection often make prolonged use of TPN a necessity. Younger gestational age, lower birth weight, and a longer duration of TPN are associated with increased likelihood of TPN-associated cholestasis. Comorbid conditions
such as sepsis, hypoxia, or immature hepatic function are commonly encountered in the preterm infant, but TPN-related factors such as taurine or carnitine deficiency may also play important roles in the development of cholestasis and subsequent hepatic disease.
The onset of TPN-associated cholestasis (TPN-AC) is usually insidious. Hepatomegaly and conjugated hyperbilirubinemia raise the suspicion of likely TPN-associated cholestasis, but other etiologies of cholestasis must be considered . Because TPN-AC is often a diagnosis of exclusion, the evaluation includes ultrasonography and possibly hepatobiliary scintigraphy, which may identify an obstructive lesion. Other considerations are inborn errors of metabolism and congenital infection. A liver biopsy may help to exclude disorders such as storage diseases; however, the histopathology seen with TPN-associated cholestasis includes portal inflammation, cholestasis, and frequently fibrosis, which are suggestive but not diagnostic findings.
Because the specific cause of liver disease associated with TPN has not been determined, the treatment remains ill defined. Provision of at least some enteral nutrition has been shown to improve cholestasis and slow the development of liver injury. Agents such as phenobarbital and ursodeoxycholic acid are frequently used to improve bile flow. Other treatment modalities involve preventing photooxidation of the TPN solution, cycling the parenteral nutrition, and modifying its composition. In its early stages, TPN-associated liver disease may be reversible if enteral nutrition can be instituted.
In older children, adolescents, and adults, TPN-associated liver injury is more likely to present with steatosis (fatty liver) than cholestasis and inflammation. The pathophysiological process responsible for the steatosis is not completely understood, but possible mechanisms include an excessive calorie-to-nitrogen ratio, an excessive glucose infusion rate, and carnitine deficiency. As with cholestatic liver injury in infants, cessation of TPN usually results in a normalization of liver enzymes.
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