Advancements in autoimmune hepatitis management: Perspectives for future guidelines

Abstract

The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine (AZA). Budesonide has shown promise in inducing a complete biochemical response (CBR) with fewer adverse effects and is considered an optional first-line treatment, particularly for patients without cirrhosis; however, it is worth noting that the design of that study favored budesonide. A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered. Current guidelines recommend mycophenolate mofetil (MMF) for patients who are intolerant to AZA. It is important to mention that the evidence supporting this recommendation is weak, primarily consisting of case series. Nevertheless, MMF has demonstrated superiority to AZA in the context of renal transplant. Recent comparative studies have shown higher CBR rates, lower therapeutic failure rates, and reduced intolerance in the MMF group. These findings may influence future guidelines, potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis. Until recently, the only alternative to corticosteroids was lifelong maintenance treatment with AZA, which comes with notable risks, such as skin cancer and lymphoma. Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies, whether relying on histological criteria, strict biochemical criteria, or a combination of both. Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo. However, these interesting findings have yet to be replicated by other research groups. Additionally, second-line drugs, such as tacrolimus, rituximab, and infliximab, should be subjected to controlled trials for further evaluation.

Keywords: Autoimmune hepatitis, Treatment, Immunosuppression, Relapse, Remission induction

Core Tip: Autoimmune hepatitis guidelines consider corticosteroids as first-line treatment, including budesonide as an option in patients without cirrhosis. Azathioprine is recommended to reduce corticosteroid doses and side effects. Nevertheless, there are concerns regarding its long-term malignancy risks. Recent publications suggest that these guidelines may be outdated. The efficacy of budesonide can be limited to patients with lower aminotransferases levels. The potential superiority of mycophenolate mofetil to azathioprine is under scrutiny. Additionally, there are controversies regarding treatment suspension, with a potential role for chloroquine for long-term maintenance treatment. Other therapeutic agents are still in the initial stages of research.