Treatment Withdrawal in Autoimmune Hepatitis

Abstract

Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disorder of unknown aetiology, which when left untreated can lead to liver cirrhosis and hepatic failure. Current treatment strategies include long-term treatment with corticosteroids and/or azathioprine. Most patients respond well to immunosuppressive therapy and treatment usually results in an asymptomatic course of AIH in remission. Nevertheless, both drugs are associated with serious side effects that can sometimes be severe and may necessitate drug withdrawal. Whether or not treatment in patients who are in longstanding remission can be discontinued is unknown. Key Messages: Available data rely on retrospective data sets and are not conclusive. Some studies indicate that a sustained remission after treatment withdrawal is feasible, whereas other studies have found relapse rates in up to 90% of patients, even in patients with established histological remission. Patients who relapse after drug withdrawal have a high probability for a re-relapse to occur. Life-long maintenance therapy should be strongly considered in these patients, since patients who have multiple relapses are more likely to progress to cirrhosis, liver transplantation and death from liver failure. Conclusion: For a majority of patients, AIH is a lifelong disease requiring permanent treatment. Patients in longstanding clinical remission on monotherapy, with complete normalisation of aminotransferases and IgG could be offered one attempt of drug withdrawal. The risk of disease progression after a single relapse appears low, while a patient's realization that infinite maintenance therapy is mandatory may improve drug adherence.

Adverse events related to low dose corticosteroids in autoimmune hepatitis

“…Currently, treatment regimens for autoimmune hepatitis are based on these trials and 44%‐75% of patients require a glucocorticosteroid‐based maintenance therapy, with or without azathioprine . Up to 30% of these patients may suffer from corticosteroid‐related side effects, including diabetes, osteoporotic fractures, cataract, hypertension, cushingoid appearance and weight gain . Corticosteroid‐specific side effects are thought to arise in autoimmune hepatitis patients on doses exceeding 7.5‐10 mg/d predniso(lo)ne when administered over several months and it is advocated to reduce the dose below this threshold to prevent adverse events .…”

“…3,4 Up to 30% of these patients may suffer from corticosteroid-related side effects, including diabetes, osteoporotic fractures, cataract, hypertension, cushingoid appearance and weight gain. 5 Corticosteroidspecific side effects are thought to arise in autoimmune hepatitis patients on doses exceeding 7.5-10 mg/d predniso(lo)ne when administered over several months and it is advocated to reduce the dose below this threshold to prevent adverse events. 6 However, studies on dose-related side effects of corticosteroids supporting this assumption have predominantly been performed in rheumatic diseases, and data on the prevalence of side effects in patients with autoimmune hepatitis on long-term corticosteroids are scarce.…”

Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation

“…Therapeutic strategies to interrupt these cycles might suppress the development and progression of chronic pathological processes. Immunosuppressive therapies with steroids and/or azathioprine slow disease progression, but have serious side effects . Thus, alternative therapies are urgently needed.…”

“…Immunosuppressive therapies with steroids and/or azathioprine slow disease progression, but have serious side effects. (3,4) Thus, alternative therapies are urgently needed.…”

Estudo randomizado e duplo cego com uso de difosfato de cloroquina para a manuntenção de remissão da hepatite autoimune apos a suspensão da imunossupressão

“…As opções terapêuticas para a manutenção sustentada da remissão da doença são escassas, incluindo monoterapia com azatioprina 2 mg/kg/dia (com retirada gradual e lenta da prednisona) (8,74,154,155) , corticosteroides em monoterapia na menor dose possível com manutenção de remissão bioquímica ou combinação de azatioprina e doses baixas de corticoides (8,74,154,155) . 10-20% (156) . Cerca de 6% daqueles que utilizam azatioprina 2 mg/kg/dia por tempo prolongado evoluem com supressão medular (e o risco é maior em pacientes cirróticos com hiperesplenismo), e 32% necessitam ajuste da dose por efeitos colaterais (1) .…”