Author: Medical Team
Medical Blog
download ArticleBackground
Cholestasis is a liver disease, defined as the restricted or inhibited bile flow from the liver. Bile is essential for digestion, helps to break down fats, absorb fat-soluble vitamins, and eliminate toxins. Cholestasis is seen in all the age groups, However the pediatric and adolescent age groups are more prone due to the immaturity of liver.
Although the precise prevalence of cholestasis in pediatric patients is unknown, there is estimated prevalence of 1 per 50,000 to 1 per 100,000 births. Children with cholestasis commonly have jaundice, pruritus, hepatosplenomegaly, and abnormal liver function. If discovered and treated early, most children with cholestasis often have a fair prognosis. On the other hand, if it is not identified and treated in a timely manner, it will negatively impact children's growth and development, result in severe and irreparable brain damage, and even cause liver cirrhosis and death.
Ursodeoxycholic acid (UDCA)
Ursodeoxycholic acid (UDCA), commonly known as ursodiol, is a naturally occurring secondary bile acid in humans. It is widely used as hepatoprotective medication and considered as the primary treatment for cholestasis for many years. UDCA works by multiple mechanisms of action, each targeting at one or more of the pathogenetic processes of cholestatic liver disorders. These mechanisms include:
(1) Protection of wounded cholangiocytes against toxic effects of bile acids.
(2) Stimulation of defective biliary production.
(3) Activation of hydrophobic bile acid detoxification.
(4) Suppression of hepatocyte apoptosis.
It is frequently used to treat adult patients with cholestatic liver illnesses, such as primary biliary cirrhosis, and cholesterol related gallstones. The majority of research have demonstrated that UDCA is safe while also being successful in reducing adult patients cholestasis symptoms.
Supporting scientific literature
Limited literature is available which showed the significance of UDCA in pediatrics with cholestasis. Out of these, 31 were carried out in China and 1 in Italy. They involved 2153 patients, of whom 1086 (50.44%) received UDCA and 1067 (49.56%) received a placebo or a blank control. These studies assessed the effects of UDCA on infantile cholestasis (cause unknown) (n = 10), Infantile Hepatitis Syndrome (IHS) (n = 8), Parenteral Nutrition Associated Cholestasis (PNAC) (n = 8), and viral hepatitis (n = 6).
Primary studies
Primary outcome |
Meta-analysis results |
Effective rate |
The efficacy rate of UDCA in children was reported in 23 trials in all. According to the findings of the meta-analysis, UDCA was superior to the placebo/control group in treating cholestasis in pediatric patients. |
Liver function Total bilirubin (TBIL)
Direct bilirubin (DBIL) |
A total of 29 studies examined the impact of UDCA on TBIL, and the findings of the meta-analysis suggested that UDCA may lower TBIL blood levels in cholestasis-affected children.
A meta-analysis of 23 studies that examined the impact of UDCA on DBIL revealed that it could lower the serum level of DBIL in cholestasis-affected kids. |
Total bile acid (TBA) |
The effect of UDCA on TBA was the subject of 18 investigations, and the findings of the meta-analysis revealed that UDCA might lower the serum level of TBA in infants with cholestasis. |
Alanine Aminotransferase (ALT) |
There were 27 studies in all that examined the impact of UDCA on ALT, and the findings of the meta-analysis suggested that UDCA may help children with cholestasis by lowering their serum ALT levels. |
Aspartate Aminotransferase (AST) |
In children with cholestasis, UDCA could lower the serum level of AST, according to the findings of a meta-analysis that included data from 11 trials that examined its effects on AST. |
Sub group analysis
Primary outcome |
Meta-analysis results |
Effective rate |
We performed subgroup analyses of the efficacy rate of UDCA by various circumstances and UDCA doses in children with cholestasis. The findings demonstrated that UDCA was superior to placebo/blank control in treating IHS, CMV hepatitis, and PNAC, while there was no discernible difference in efficacy for cholestasis brought on by various diseases. |
Liver functions Total bilirubin (TBIL)
|
In children with IHS, CMV hepatitis, and PNAC, subgroup analysis for TBIL revealed that UDCA could lower the increased blood TBIL level, and its efficacy on decreasing TBIL was superior to that of the placebo/blank control. |
Direct bilirubin (DBIL) |
In children with IHS, CMV hepatitis, and PNAC, subgroup analysis for DBIL revealed that UDCA may lower the growing serum DBIL levels, and its efficacy was superior to that of the placebo/blank control. |
Total bile acid (TBA) |
The findings of the TBA subgroup analysis revealed that UDCA had a better effect than the placebo/blank control in lowering the rising serum TBA in children with IHS, CMV hepatitis, and PNAC. |
Alanine Aminotransferase (ALT) |
The UDCA's effects were superior to those of the placebo/blank control in children with IHS, CMV hepatitis, and PNAC, according to the results of the subgroup analysis for ALT. |
Aspartate Aminotransferase (AST) |
According to the AST subgroup analysis, UDCA was able to lower the high serum AST levels in kids with PNAC, and its efficacy in reducing AST levels was superior to that of the placebo/blank control. |
Conclusion
Scientific studies suggested that UDCA was both safe and effective for children with cholestasis, but doctors should proceed with caution and only administer 10 mg/kg/d initially.
UDCA effectively treats pediatric cholestasis and is well tolerated by children. However, other studies thought that UDCA was inefficient and dangerous in newborns and babies with cholestasis and might be linked to serious consequences (cirrhosis, hepatocyte failure, etc.), the progression of the disease, and death, especially when taking higher doses (20-40 mg/kg)/d).
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