Advancing Biologic Therapy for Refractory Autoimmune Hepatitis

Czaja, Albert J.

doi:10.1007/s10620-021-07378-4

Cited by 7 publications

(10 citation statements)

References 385 publications

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“…The majority of patients achieve remission with established first-to- third-line treatments (azathioprine, mycophenolate mofetil and calcineurin inhibitors) [ 2 ]. In case of intolerance or insufficient response to established drugs, treatment options are limited and novel treatment approaches are urgently needed [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series

Kolev

Sarbu

Möller

et al. 2023

Journal of Translational Autoimmunity

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Section: Introductionmentioning

confidence: 99%

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series

Kolev

Sarbu

Möller

et al. 2023

Journal of Translational Autoimmunity

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“…Current studies mainly target TNF-α and IL-2. 238 Studies have shown that infliximab, an anti-TNF-α monoclonal antibody, can achieve laboratory remission in refractory AIH patients, but some patients develop severe infectious complications. 239 In addition, ~1 in 120 AIH patients treated with infliximab experienced hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

CD4+ T-cell subsets in autoimmune hepatitis: A review

Chen,

Han,

Fan

et al. 2023

Hepatology Communications

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Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that can lead to hepatocyte destruction, inflammation, liver fibrosis, cirrhosis, and liver failure. The diagnosis of AIH requires the identification of lymphoblast cell interface hepatitis and serum biochemical abnormalities, as well as the exclusion of related diseases. According to different specific autoantibodies, AIH can be divided into AIH-1 and AIH-2. The first-line treatment for AIH is a corticosteroid and azathioprine regimen, and patients with liver failure require liver transplantation. However, the long-term use of corticosteroids has obvious side effects, and patients are prone to relapse after drug withdrawal. Autoimmune diseases are characterized by an imbalance in immune tolerance of self-antigens, activation of autoreactive T cells, overactivity of B cells, and increased production of autoantibodies. CD4+ T cells are key players in adaptive immunity and can secrete cytokines, activate B cells to produce antibodies, and influence the cytotoxicity of CD8+ T cells. According to their characteristics, CD4+ T cells can be divided into different subsets. In this review, we discuss the changes in T helper (Th)1, Th2, Th17, Th9, Th22, regulatory T cell, T follicular helper, and T peripheral helper cells and their related factors in AIH and discuss the therapeutic potential of targeting CD4+ T-cell subsets in AIH.

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“… 57 Several targeted immunomodulatory treatments have gained approval for various autoimmune diseases, including plaque psoriasis, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. 38 Existing immunomodulatory treatments for these autoimmune diseases may provide a rationale for use in patients with AIH, 38 and they may already be used in patients with indicated autoimmune comorbidities. Among these treatments, rituximab, a monoclonal antibody that depletes B cells by targeting CD20, has been associated with improvements in patients with difficult-to-manage AIH.…”

Section: Potential For Targeted Treatment Of Aihmentioning

confidence: 99%

“…These include tacrolimus, mycophenolate mofetil (MMF), and biologics. 2 38 Patients with AIH can be treated with MMF as both first-line treatment option and second-line in patients who are unable to tolerate azathioprine. 2 39 Compared with azathioprine, MMF has been associated with better outcomes in patients with treatment-naïve AIH, 40 41 and a meta-analysis reported a pooled response rate of 58% for MMF.…”

Section: Introductionmentioning

confidence: 99%

“… 43 Further, potential salvage treatments for treatment-refractory AIH include cyclosporine, rituximab, and infliximab, an anti-TNF-α monoclonal antibody. 2 38 44 It should be noted that, although the event is rare, TNF-α inhibitors can potentially induce de novo AIH. 45 46 Drug-induced AIH can present with characteristics of AIH, including positive autoantibodies and interface hepatitis on liver biopsy.…”

Section: Introductionmentioning

confidence: 99%

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Autoimmune hepatitis: Current and future therapies

Reau,

Lammert,

Weinberg

2024

Hepatology Communications

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Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.

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Advancing Biologic Therapy for Refractory Autoimmune Hepatitis

Cited by 7 publications

References 385 publications

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series

CD4+ T-cell subsets in autoimmune hepatitis: A review

Autoimmune hepatitis: Current and future therapies

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