Effectiveness and Safety of Everolimus in the Treatment of Autoimmune Hepatitis Related to Anti-Hepatitis C Virus Therapy After Liver Transplant: Three Case Reports

Casanovas, Teresa; Argudo, A. Montero; Peña-Cala, Maria Carmen

doi:10.1016/j.transproceed.2011.05.028

Cited by 17 publications

(9 citation statements)

References 28 publications

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“…Since low dose calcineurin inhibition is sufficient for the treatment of AIH and does not compromise renal function, little need exists for sirolimus or everolimus. Sirolimus and everolimus have been used successfully in the treatment of recurrent AIH or interferon-induced AIH after OLT (see below) [196,197].…”

Section: Sirolimusmentioning

confidence: 99%

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Autoimmune hepatitis

Sahebjam

Vierling

2015

Front. Med.

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Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte-specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.

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Section: Sirolimusmentioning

confidence: 99%

“…Minimal adverse events were noted. Everolimus was successfully used to treat 3 patients with de novo AIH generated by pegylated interferon treatment of recurrent HCV after OLT [197]. One patient had a sustained viral response; the other 2 were nonresponders.…”

Section: Recurrent Autoimmune Hepatitis After Transplantationmentioning

confidence: 99%

Autoimmune hepatitis

Sahebjam

Vierling

2015

Front. Med.

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“…19,64,67 Adding everolimus may also be an option. 68 Whether this AIH-like hepatitis is a variant of ACR or is de novo AIH is a matter of debate. 67 …”

Section: Rejection and Autoimmune Complicationsmentioning

confidence: 99%

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Bunchorntavakul¹,

Reddy²

2014

JCTH

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Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/ progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.

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“…Several initiatives recently enacted by the Australian government, as well as cheaper generic availability of pharmaceuticals after patent expiry, have introduced cost-savings measures and these introduce uncertainty about future pricing structures and PBS expenditures. However, by considering the increasing number of kidney transplant operations, functioning kidney transplants in the community and potential for widening of the subsidized indications, particularly for mycophenolate [47][48][49], tacrolimus [50] and everolimus [51][52][53], immunosuppressant expenditure will continue to rise into the future. It is not likely that generic formulations …”

Section: Discussionmentioning

confidence: 99%