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Phenobarbital can aggravate a cholestatic bile acid pattern in infants with obstructive cholangiopathy
A Nemeth1, S A Wikström, B Strandvik
1Department of Pediatrics, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Insights
Phenobarbital treatment worsened bile acid excretion in infants with intrahepatic cholestasis, contrary to expectations. This study suggests phenobarbital is not recommended for routine use in pediatric cholestatic liver disease.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Pharmacology
Background:
- Intrahepatic cholestasis in infants presents with significantly elevated urinary bile acids.
- Primary bile acids and specific hydroxylated/ketonic forms are predominant in affected infants.
Observation:
- Phenobarbital administration (10 mg/kg) was studied in four boys with intrahepatic cholestasis.
- One child was assessed with and without cirrhosis, over treatment periods ranging from 3 weeks to 3 years.
Findings:
- Phenobarbital treatment led to a further increase in urinary bile acid excretion across most types, excluding secondary bile acids.
- Absolute sulfated bile acid amounts did not rise, and their relative percentage decreased significantly.
- Liver function tests showed minimal improvement, with only a decrease in serum bilirubin, suggesting a worsening cholestatic state.
Implications:
- Phenobarbital may exacerbate the cholestatic condition in infants and children.
- Routine use of phenobarbital in pediatric intrahepatic cholestasis is not advised based on current evidence.
- Further research is needed to understand phenobarbital's complex effects on bile acid metabolism in cholestasis.
Abstract:
The effect of phenobarbital on urinary bile acid excretion in intrahepatic cholestasis was studied in four boys 4-43 months of age who received 10 mg/kg of body weight of phenobarbital for a period of 3 weeks-3 years. One child was observed at two different periods: with and without histologically proven cirrhosis. Before the treatment period, the infants excreted 10-fold higher amounts of bile acids in urine than healthy children. The primary bile acids predominated, and there were also increased amounts of polyhydroxylated bile acids, 3 beta-hydroxy-5-cholenoic acid, and ketonic bile acids but small amounts of secondary bile acids. After the phenobarbital treatment, the patients further increased their urinary bile acid excretion, including all kinds of bile acids except the secondary ones. The sulfated fraction did not increase in absolute amounts, and its relative percentage decreased from a mean of 60-33%. Liver function test results generally did not improve, although serum concentration of bilirubin decreased. Most of these changes suggested a worsening of the cholestatic state after phenobarbital treatment. The results indicate that at our present state of knowledge, phenobarbital should not be given routinely to infants or children with intrahepatic cholestasis.