The Effect of Oral Silymarin on Remdesivir-Induced Hepatotoxicity and Clinical Course in Covid-19 Patients; A Double-Blind Randomized Controlled Trial

Remdesivir is a nucleoside inhibitor of RNA polymerase with the antiviral activity used in the treatment of COVID-19 pneumonia. One of the remdesivir side effects is hepatotoxicity. Given the growing body of data supporting silymarin's antiviral and hepatoprotective properties, the present research sought to explore the impact of silymarin on laboratory parameters, frequency of symptoms, and liver enzymes in COVID-19 patients.

In this double-blind randomized clinical trial 70 patients were divided into two groups of 35. Intervention group received remdesivir + 140 mg Silymarin, 3 times, daily for 1 week, and the control group received remdesivir + placebo. Patients' symptoms and laboratory findings were assessed at baseline and 5,7,10, and 14 days’ post enrollment.

Liver enzymes level (aspartate aminotransferase, and alkaline phosphatase), and lactate dehydrogenase were significantly decreased in the intervention group (p < 0.05). Among the clinical symptoms, cough (p=0.03), shortness of breath (p= 0.006), headache (p=0.01), and muscle pain (p=0.03) were significantly lower in the treatment group comparing to the control group. Moreover, the severity of disease in the intervention group was substantially lower than that among the control group.

Concomitant use of remdesivir with silymarin might reduce hepatotoxicity and ultimately improve the patients' condition. More clinical trials with different dosages and larger sample sizes are recommended.