Long-Term Prednisone Use Increases Hepatocellular Carcinoma Risk in Autoimmune Hepatitis Cirrhosis: A Retrospective Cohort Study

TL;DR

Long-term prednisone use in autoimmune hepatitis cirrhosis patients increases the risk of developing liver cancer.

Contribution

This study identifies prednisone as an independent risk factor for hepatocellular carcinoma in AIH-cirrhosis patients.

Findings

25.4% of prednisone-exposed patients developed HCC compared to 9.7% of controls.

Prednisone was confirmed as an independent risk factor with an adjusted hazard ratio of 3.36.

The risk is linked to prednisone's immunosuppressive and metabolic effects.

Abstract

Autoimmune hepatitis (AIH) is an immune-mediated liver condition marked by progressive inflammation, piecemeal necrosis, and eventual cirrhosis. Prednisone has long served as the foundational AIH therapy. However, its prolonged use warrants closer evaluation regarding long-term outcomes. Among cirrhotic patients, the combination of chronic inflammatory and tumor-promoting changes may synergize to compromise immunity increasing susceptibility to hepatocellular carcinoma (HCC). In this context, adding immunosuppressive burden of corticosteroids may influence cancer risk in ways not well investigated. We investigated the effect of dose-dependent prednisone exposure on HCC risk in AIH-cirrhosis patients.

We conducted a retrospective analysis of 121 adults with AIH-cirrhosis evaluated at Cedars-Sinai. Patients were categorized based on prednisone exposure: (≥7.5 mg/day for ≥6 months following cirrhosis diagnosis) exposure vs subthreshold exposure (with or without alternative therapies). The primary outcome was the HCC incidence rate and hazard ratio derived from Cox proportional hazards models. Secondary outcomes included HCC incidence using multivariable models adjusted per demographics and disease severity.

In unadjusted time-to-event analysis, prednisone use shortened HCC-free survival, the results indicated HCC developed in 25.4% of the prednisone group vs 9.7% of controls (P = .030). Multivariable analysis adjusted per age, gender, ethnicity, Child-Turcotte-Pugh, and alpha-fetoprotein confirmed prednisone as an independent risk factor (adjusted hazard ratio: 3.36; P = .040).

The study findings suggested that prolonged prednisone exposure in patients with AIH-cirrhosis independently contributes to HCC development. This association appears to be supported by mechanistic pathways, driven by prednisone’s dose-dependent immunosuppressive and metabolic effects, disrupting immune surveillance, promoting hepatic fibrosis, and oncogenic pathways.

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