Alcohol Use, Cholesterol Tied to Liver Injury With Pulse Steroid Therapy
Notably, a history of alcohol abuse and hyperlipidemia — higher-than-normal blood levels of fatty molecules such as cholesterol — were each associated with an increased risk of liver injury after the treatment.
These findings support the importance of closely monitoring liver health after a short course of high-dose methylprednisolone, particularly among patients with risk factors, the researchers noted.
The study, “Evaluation of liver injury in multiple sclerosis patients receiving pulsed steroid therapy,” was published in the journal Multiple Sclerosis and Related Disorders.
Relapsing forms of MS are characterized by periods of disease exacerbations, including the appearance of new or worsening disease symptoms that last for at least 24 hours. These flares are due to active inflammation in the central nervous system (brain and spinal cord).
Glucocorticoids such as methylprednisolone (sold as Solu-Medrol, among other brands) are often used as a first-line treatment to help suppress inflammation and ease symptoms during a relapse. Short periods of these medications at high dose, called pulsed therapy, work to quickly resolve severe relapses.
But such treatment can be associated with significant side effects, including high blood-sugar levels, a fast heart rate, gastrointestinal problems, and immune cell changes. The use of high-dose methylprednisolone also has been linked to liver injury, but studies into this connection when treating an MS relapse show conflicting results.
Researchers in Iran investigated the frequency and severity of liver injury after pulsed methylprednisolone therapy in MS patients, as well as potential risk factors for the development of this side effect.
In total, 314 adults — 209 women and 105 men, with a mean age of 32.4 — with MS were analyzed; all received pulsed methylprednisolone treatment for their relapses at the Sina Hospital, in Tehran, between May 2020 and May 2021.
The therapy was administered directly into the bloodstream (intravenous administration) at a maximum daily dose of 1,000 mg for five days, after which oral prednisolone, another glucocorticoid, was given and slowly tapered over the next 10 to 15 days.
Liver injury was determined if patients showed blood levels of alanine aminotransferase (ALT) — a liver enzyme and biomarker of liver inflammation — above 45 international units per liter (IU/L) after treatment. Levels of other compounds indicative of liver function, including bilirubin and the liver enzymes aspartate aminotransferase and alkaline phosphatase, were also measured.
All these liver function tests were performed before treatment, shortly after treatment, then one week and one month after the end of the treatment. In the presence of liver damage signs, tests were repeated every two weeks until values were normalized.
Results showed that patients’ scores on the expanded disability status scale (EDSS, a measure of disability) significantly lowered after pulse methylprednisolone therapy, indicating that the treatment successfully eased MS-associated disability.
Nine (2.86%) patients, seven women and two men with a mean age was 36.1, showed signs of liver injury after methylprednisolone therapy, none of which were severe.
Their average ALT values were normal (36.6 IU/L) before treatment and rose to 233.2 IU/L immediately after the pulse therapy. Higher-than-normal values subsided a week after treatment (average of 54 IU/L), and returned to a normal range after one month (average of 35.3 IU/L).
Similar patterns were seen for the other liver enzymes, while bilirubin levels were normal both before and after treatment.
The cause of liver injury, or the likelihood that it was caused by methylprednisolone treatment, was assessed with two different measures: the Naranjo scale and the World Health Organization (WHO)-Uppsala Monitoring Centre (UMC) system. According to the Naranjo scale, causality between liver damage and pulse methylprednisolone therapy was classified as probable in all nine cases; based on the WHO-UMC, causality was certain in eight cases and possible in one.
While most clinical and demographic features did not differ significantly between patients with or without liver injury, a significantly greater incidence of hyperlipidemia, alcohol abuse (consumption on a daily basis), and non-alcoholic fatty liver disease (NAFLD) was found among those with liver damage signs.
NAFLD comprises a range of liver conditions characterized by too much fat in liver cells that is not caused by alcohol use.
When adjusted for potential influencing factors, alcohol abuse and hyperlipidemia were significant risk factors for liver injury after pulse methylprednisolone therapy. Specifically, a history of alcohol abuse was linked to a 36 times higher risk of liver injury post-treatment, and hyperlipidemia was associated with a six-fold increased risk.
Overall, the findings highlight “the importance of a close follow-up of the liver function tests in MS patients following pulsed methylprednisolone therapy, particularly in patients with NAFLD, hyperlipidemia, and history of alcohol-abusing,” the researchers wrote.
Since the study was not long term, later signs of liver injury cannot be ruled out, marking one of the study’s limitations. Another limitation was that tapering of subsequent oral prednisolone may have influenced the results, the team noted.
According to the team, larger multicenter studies, with a longer follow-up, are needed to confirm these findings.