Autoimmune-Like Hepatitis Triggered by Methylprednisolone: A Case Report about the Paradox of Treating DILI with the Offending Drug.
Simas Diogo D, Gonçalves André Ruge AR, Gomes Plácido P, Russo Pedro P et al.
Acute liver failure with an autoimmune phenotype can result from various causes, including autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) with autoimmune features. Rarely, corticosteroids themselves may trigger autoimmune-like liver injury, further complicating the differentiation between AIH and DILI. We report a 57-year-old woman with multiple sclerosis who received high-dose intravenous methylprednisolone (1 g/day for 5 days) 6 weeks prior to presentation. She was admitted with severe fatigue, jaundice, asterixis, and laboratory findings consistent with acute liver failure (total bilirubin 12.6 mg/dL, direct bilirubin 5.88 mg/dL, INR 1.95, and elevated ammonia). Abdominal and brain computed tomography were unremarkable. IgG levels were 2,506 mg/dL (upper limit 1,600), with positive antinuclear antibodies (titer 1:320) and negative anti-smooth muscle and anti-mitochondrial antibodies. Extensive workup excluded viral hepatitis, metabolic disorders, and other common causes of liver injury. Transjugular liver biopsy demonstrated moderate periportal and severe lobular hepatitis with plasmacytic infiltration and centrilobular necrosis, without significant fibrosis, consistent with an autoimmune-like pattern. The patient received prednisolone (1 mg/kg/day) with rapid biochemical improvement. Azathioprine was introduced during hospitalization but later discontinued by the patient. Long-term follow-up showed normalization of liver tests and IgG levels without relapse, supporting a diagnosis of drug-induced autoimmune-like hepatitis (DI-ALH). The temporal association with methylprednisolone, exclusion of alternative etiologies, and the absence of relapse after discontinuation of immunosuppressive therapy suggest corticosteroid-DI-ALH rather than primary AIH. This paradoxical presentation is rare, as corticosteroids are generally used therapeutically in AIH or in severe DI-ALH rather than as a causative agent, highlighting the need for awareness of atypical drug-induced hepatotoxicity. This case underscores the diagnostic challenges in distinguishing DI-ALH from AIH, particularly when corticosteroids are implicated, and emphasizes the importance of long-term follow-up to confirm resolution and guide management.