AIH: Which Alternative for Difficult-to-Treat Patients?

Abstract

Background: Oftentimes we are expected to make difficult decision when patients with autoimmune hepatitis (AIH) present themselves before us. Among these cases, advanced liver cirrhosis, fulminant AIH with hepatic failure or pregnancy with highly active AIH will pose challenges on their own. In patients where standard treatment has failed, the risk of disease progression including liver transplantation has to be weighed against the risk of drug-related side effects, including infectious complications. Key Messages: Standard treatment of AIH includes the use of drugs like corticosteroids and usually azathioprine. However, up to 15% of patients will require second-line treatment. There are no prospective studies evaluating second- or third-line treatment regimens in AIH. In our opinion, it is essential to differentiate between those patients who are intolerant and those who do not respond sufficiently to standard treatment. For patients intolerant to prednisolone due to steroid-induced side effects, budesonide may be a feasible alternative, unless liver cirrhosis forbids its use. Our experience indicates that 6-mercaptopurine may be given as an alternative to azathioprine, especially in cases of gastrointestinal side effects, with good tolerance and response rates of up to 70%. As a more expensive alternative, mycophenolat mofetil (MMF) has been shown to effectively suppress disease activity in a majority of patients intolerant to azathioprine. Of note, MMF is contraindicated in pregnancy. In patients with insufficient response to azathioprine, the dose should be increased up to 2.5 mg/kg of body weight, and measurement of azathioprine metabolites (6TGN and MMP) may aid the optimal dosage. Several other immunosuppressive treatment strategies have been tested and published in small case series. These include the calcineurin inhibitors cyclosporine A and tacrolimus, mTOR inhibitors, anti-tumor necrosis factor α treatment with infliximab, rituximab as well as cyclophosphamide. Conclusions: It is difficult to tell whether 1 strategy is superior to another in the case of difficult-to-treat AIH patients. Intolerance should be differentiated from insufficient response to standard treatment. The choice of second- and third-line treatment will depend on the comorbidities, patient's choice after informed consent and also local expertise.

Enfermedades hepáticas y embarazo

“…El mofetilo micofenolato debería suspenderse antes del embarazo y no ser utilizado durante la gestación, ya que se ha asociado con aumento de la teratogenicidad (30,39,40). Los inhibidores de calcineurina pueden utilizarse de manera segura durante la gestación, de acuerdo con los datos obtenidos de gestantes trasplantadas (30,40).…”

“…El mofetilo micofenolato debería suspenderse antes del embarazo y no ser utilizado durante la gestación, ya que se ha asociado con aumento de la teratogenicidad (30,39,40). Los inhibidores de calcineurina pueden utilizarse de manera segura durante la gestación, de acuerdo con los datos obtenidos de gestantes trasplantadas (30,40). Con el fin de disminuir los riesgos de complicaciones, estas pacientes idealmente deben planear su embarazo y tener control de la actividad inflamatoria por lo menos 1 año antes de embarazarse, recibir tratamiento durante toda la gestación, recibir atención del parto en centros de alta complejidad y realizar controles estrechos durante el embarazo y el posparto, tanto por obstetricia como por hepatología (2,30,32,33,(38)(39)(40).…”

“…La terapia inmunosupresora con esteroides y agentes, como la azatioprina, son el pilar fundamental del tratamiento de la hepatitis autoinmune (30,36,40). Sin embargo, en el embarazo, el manejo óptimo no está bien establecido, lo que sí está claro es que estas pacientes requieren inmunosupresión estable durante todo el embarazo, con mayor vigilancia en el período posparto (30,32,33,38,40,41).…”

CQMUH‐011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes

“…Drug-related side effects, including increased risk of infections and tumors (Yang et al, 2015), cause the majority of patients to often experience a recurrence in AIH after ceasing corticosteroid treatment (Maruoka et al, 2013;Vergani & Mieli-Vergani, 2011). Moreover, special groups, such as pregnant women, elderly patients, or those with poor reactions to drugs, require a substitute from the traditional treatment (Sebode & Schramm, 2015). Therefore, new effective alternative treatment options need to be explored to overcome the therapeutic insufficiency.…”

Overexpression of KLF14 protects against immune-mediated hepatic injury in mice

“…For those patients not responsive to steroids or azathioprine, second-line therapies can prevent progression of the disease. Mycophenolate mofetil, rapamycin, and infliximab have been shown to achieve biochemical improvements and to be promising treatment alternatives for hepatitis [2].…”