A new study published in the journal ofGastro Hep Advancesfound that long-term prednisone therapy in patients with autoimmune hepatitis cirrhosis (AIH) to increase the risk of developing hepatocellular carcinoma (HCC). Autoimmune hepatitis is characterized by progressive inflammation, piecemeal necrosis, and eventual cirrhosis if left untreated. Prednisone, a corticosteroid, has long been the cornerstone of AIH management due to its ability to suppress the immune system and control inflammation. However, the chronic use of corticosteroids carries well-recognized risks, and its impact on long-term cancer outcomes in patients with AIH-related cirrhosis has remained poorly understood. This study retrospectively analyzed medical records of 121 adults with AIH-cirrhosis treated at Cedars-Sinai. The patients were divided into 2 groups based on their prednisone exposure as high-exposure group taking Prednisone ≥7.5 mg/day for at least 6 months and subthreshold group, where the patients receiving lower or shorter courses of prednisone, with or without alternative therapies. The primary outcome assessed was the incidence of HCC, while secondary analyses adjusted for demographic and disease-specific variables, including age, gender, ethnicity, Child-Turcotte-Pugh (CTP) score, and alpha-fetoprotein (AFP) levels. Among those with prolonged prednisone exposure, 25.4% developed HCC compared to just 9.7% in the subthreshold group. This difference in HCC-free survival reached statistical significance (p=0.030). After accounting for confounding factors, multivariable Cox regression confirmed that prednisone use remained an independent predictor of HCC development. The adjusted hazard ratio (HR) was 3.36 (p=0.040), meaning patients on long-term, higher-dose prednisone had more than triple the risk of liver cancer when compared to their counterparts. The raw incidence percentages (25.4% vs. 9.7%), and the survival analysis demonstrated how HCC-free survival declined more rapidly in the prednisone group. Adjusted models further emphasized prednisone’s role, independent of disease severity or demographic differences. The study suggests that prednisone’s immunosuppressive and metabolic effects may disrupt immune surveillance, accelerate fibrosis, and activate oncogenic pathways, which could explain the elevated HCC risk. While corticosteroids remain necessary for many AIH patients, these findings indicate that clinicians should carefully weigh long-term prednisone exposure in cirrhotic patients and consider alternative or adjunctive immunosuppressants. Overall, this research highlighted the urgent need for closer monitoring of AIH-cirrhosis patients receiving chronic prednisone therapy. Liu, J., Hemadeh, R., Attia, A. M., Danpanichkul, P., Adetyan, H., Kim, N., Yalda, T., Yang, J. D., Alsudaney, M., & Ayoub, W. (2025). Long-term prednisone use increases hepatocellular carcinoma risk in autoimmune hepatitis cirrhosis: A retrospective cohort study. Gastro Hep Advances, 100784,.https://doi.org/10.1016/j.gastha.2025.100784