Autoimmune hepatitis: Current and future therapeutic options

Abstract

Autoimmune hepatitis (AIH) is a rare immune‐mediated liver disease with few major advances in treatment options over the last several decades. Available options are effective in most patients albeit are imprecise in their mechanisms. Novel and more tolerable induction regimens and alternative options for management of patients intolerant or with suboptimal response to traditional therapies including in the post‐transplant setting remain an important unmet need. This review aims to summarize recent data on pharmacological options and investigational drugs in development for patients with AIH. Standard therapy using prednisone with or without azathioprine remains the mainstay of therapy and is effective in most patients. Budesonide may be considered for induction in early disease and in those with mild fibrosis, but has not been approved for maintenance therapy. Mycophenolate mofetil (MMF) in combination with steroids might be an alternative first‐line therapy, but results from a randomized trial are awaited. MMF as a second‐line maintenance agent has moderate efficacy though more frequent adverse events in patients with cirrhosis may be seen. Tacrolimus may be an equally effective second‐line option particularly in non‐responders, but data remain limited. Management of recurrent AIH post‐liver transplantation remains controversial with insufficient data to support long‐term steroid use. Moving forward, expanding the scope of therapeutic options to include biologics including B‐cell depleting agents may be a promising step. Recent insights in understanding the pathogenesis of AIH could serve as a basis for future therapies, including the elucidation of different immunoregulatory pathways and the potential role of the intestinal microbiome.

Regulatory T Cells in Autoimmune Hepatitis: Unveiling Their Roles in Mouse Models and Patients

“…However, not all patients respond well to this treatment, and most will develop disease relapse after drug withdrawal (39). Immunoregulatory therapy has also been explored as a potential therapy for AIH; however, it has not yet been clinically applied (6,40,41). Much research effort has been given in recent decades to comprehensively understand the pathogenesis of AIH and to find potential therapeutic targets (42,43).…”

“…AIH is a complex multifactorial polygenic disorder that is thought to be caused by the interaction between triggers and environmental factors in genetically susceptible individuals, leading to the loss of tolerance against one's own liver antigens (4,5). Standard immunosuppressive treatment approaches have remained static for decades; these treatments are effective in most patients, although their mechanisms are unclear (6). Many patients with AIH must receive long-term immunosuppressive treatment to prevent disease relapse (7).…”

Microarray‐based transcriptional profiling of a mouse model of autoimmune hepatitis

“…AIH, a type of immune-mediated injury targeting liver parenchyma, has a high prevalence in Europe and the United States [22]. However, an efficient cure for AIH is presently lacking.…”

Clinical Features of Chronic Inflammatory Demyelinating Polyneuropathy With Autoimmune Hepatitis

“…After treatment, the patient's 20-year survival rate reached 80%, and the life expectancy is not significantly different from that of normal healthy people matched by gender and age. Absolute indications for treatment include serum aspartate transaminase (AST) ≥ 10 times the upper limit of normal, or serum AST ≥ 5 times the upper limit of normal, and γ-globulin ≥ 2 times the upper limit of normal; histological examination showed bridging necrosis or multi-lobular necro-sis [6,21,22]. The patient's liver function was normal and no histological examination was performed.…”