Methylprednisolone reduces liver damage signs in cholestasis infants
Findings support role of inflammation in bile duct injury in cholestasis
Two weeks of oral methylprednisolone twice a day as an add-therapy significantly lowered signs of liver damage and inflammation among infants with cholestasis, a small clinical trial suggests.
Methylprednisolone is a lab-made steroid prescribed primarily for its anti-inflammatory and immunosuppressive effects. The findings support inflammation’s role in the bile duct injury that takes place in cholestasis.
“The results of this study demonstrate opportunities for the development of new medical interventions aimed at suppressing specific immune responses,” the researchers wrote.
The results were published in Heliyon, in the study “Effectiveness of oral methylprednisolone as adjuvant therapy for clinical improvement, biochemical markers, and inflammation in infants with cholestasis.”
Cholestasis refers to a disruption in the flow of bile, a digestive fluid produced by the liver that helps break down certain fatty molecules and proteins. Common cholestasis symptoms include dark-colored urine, pale stools, itchy skin, and a yellowing of the skin or whites of the eyes, called jaundice.
There are several causes of cholestasis, but the most common in infants is biliary atresia, wherein a blockage occurs in the bile ducts, which are tubes that carry bile from the liver to the intestines. When the flow of bile is slowed or stopped, it can build up and cause liver damage and fibrosis. The toxic accumulation of bile acids can also trigger an inflammatory response, which may further aggravate liver injury.
Testing methylprednisolone’s anti-inflammatory properties
Researchers in Indonesia conducted a placebo-controlled clinical trial (ISRCTN45080388) to evaluate methylprednisolone’s anti-inflammatory properties to study its effect as an add-on therapy in infants with cholestasis. A total of 38 infants, mean age 8-9 weeks, were randomly assigned to either a placebo or oral methylprednisolone at 2 mg/kg, divided into two doses taken in the morning and afternoon every day for two weeks. Both groups received ursodeoxycholic acid (UDCA), a standard treatment for cholestasis that’s sold as Urso and Actigall.
All the participants showed signs of an enlarged liver. Liver biopsies performed on 27 patients detected cholestasis outside the liver (extrahepatic) in six (42.9%) methylprednisolone-assigned patients and four (33.3%) placebo patients.
To assess efficacy, researchers measured blood levels of liver damage markers before and after treatment, including direct bilirubin, total bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transferase (GGT). Several markers for inflammation were also assessed.
After two weeks, direct bilirubin levels in both groups significantly dropped, indicating a reduction in liver damage, but the final levels were lower in the methylprednisolone than the placebo group, 3.45 vs. 5.96 mg/deciliter (mg/dL). Similar findings were observed for total bilirubin and AST. GGT worsened after treatment in both groups, but its final levels were lower with methylprednisolone over the placebo (208.5 vs. 248.5 U/L).
Lastly, in the methylprednisolone group, levels of inflammatory markers, particularly interleukin-10 and IFN-gamma, also significantly dropped, but didn’t in the placebo group.
This study was the first “to evaluate the effectiveness of methylprednisolone in improving jaundice, bilirubin levels, liver function tests, and inflammatory biomarkers in infants with cholestasis,” the researchers wrote. “Additional multicenter studies are required considering the small number of laboratory values, lack of clinical and histological [tissue] data, and the short follow-up time in this study.”
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