Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

Czaja, Albert J.

doi:10.2174/187152812803251006

Cited by 17 publications

(17 citation statements)

References 175 publications

(339 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Publications, comprised of anecdotal reports and small series of highly selected patients, have reported the safety and efficacy of 6-mercaptopurine (6-MP), cyclosporine (CSA), tacrolimus (TAC), sirolimus, mycophenolate mofetil (MMF) or mycophenolic acid (MA), ursodeoxycholic acid, methotrexate, cyclophosphamide, anti-TNFα agents, rituximab and abatacept as alternative therapies in AIH. The details of these alternative therapies have been the subject of recent reviews [6,120,131,133,147,[162][163][164][165][166][167][168][169][170][171][172][173][174][175][176]. To date, no randomized controlled trials of alternative therapies in AIH have been conducted.…”

Section: Alternative Immunosuppressive Therapiesmentioning

confidence: 99%

“…Serum creatinine levels did not increase. Overall, the empiric, uncontrolled experiences with CSA therapy for AIH patients, especially those failing to respond to conventional steroids and azathioprine, indicate that CSA is a safe and effective alternative therapy [171,[188][189][190][191][192]. A potential advantage of CSA is that it has a wider therapeutic range of effective serum concentrations than tacrolimus, which facilitates adjustment of doses to achieve maximum efficacy with optimal safety.…”

Section: Cyclosporinementioning

confidence: 99%

See 1 more Smart Citation

Autoimmune hepatitis

Sahebjam

Vierling

2015

Front. Med.

View full text Add to dashboard Cite

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.

show abstract

Section: Alternative Immunosuppressive Therapiesmentioning

confidence: 99%

Section: Cyclosporinementioning

confidence: 99%

Autoimmune hepatitis

Sahebjam

Vierling

2015

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Increased doses of the original drugs or the introduction of different immunosuppressive agents (mycophenolate mofetil or calcineurin inhibitors) are strategies that warrant formal evaluation. 264,265 Young adults with autoimmune hepatitis aged <40 years and those with HLA DRB1*0301 can be slow or poor responders to conventional therapy, 18,98,266 and they may require an enhanced treatment regimen (high dose therapy, calcineurin inhibitors, or mycophenolate mofetil) at the time of presentation. 267,268 Alternatively, elderly patients aged ≥60 years and individuals with HLA DRB1*0401 can respond rapidly to standard therapy, 18,266,269 and they may require less intense treatment (low dose therapy or budesonide).…”

Section: Management Perspectivesmentioning

confidence: 99%

Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis

Czaja

2014

Aliment Pharmacol Ther

View full text Add to dashboard Cite

SummaryBackgroundImmunosuppressive treatment of autoimmune hepatitis can prevent or reverse hepatic fibrosis, but these anti‐fibrotic effects are inconsistent secondary gains.AimTo describe the anti‐fibrotic effects of current therapies for autoimmune hepatitis, discuss the pathogenic mechanisms of hepatic fibrosis that might be targeted by anti‐fibrotic interventions, indicate the non‐invasive diagnostic tests of hepatic fibrosis that must be validated in autoimmune hepatitis and to suggest promising treatment opportunities.MethodsStudies cited in PubMed from 1972 to 2013 for autoimmune hepatitis, hepatic fibrosis, cirrhosis, anti‐fibrotic therapy and non‐invasive tests of hepatic fibrosis were selected.ResultsHepatic fibrosis improves in 53–57% of corticosteroid‐treated patients with autoimmune hepatitis; progressive fibrosis slows or is prevented in 79%; and cirrhosis may be reversed. Progressive hepatic fibrosis is associated with liver inflammation, and the inability to fully suppress inflammatory activity within 12 months is associated with progression to cirrhosis (54%) and death or need for liver transplantation (15%). Liver tissue examination remains the gold standard for assessing hepatic fibrosis, but laboratory and radiological tests may be useful non‐invasive methods to measure the fibrotic response. Severe liver inflammation can confound radiological assessments, and the preferred non‐invasive test in autoimmune hepatitis is uncertain. Individualised treatment adjustments and adjunctive anti‐fibrotic therapies are poised for study in this disease.ConclusionsThe prevention and reversal of hepatic fibrosis are achievable objectives in autoimmune hepatitis. Strategies that evaluate individualised therapies adjusted to the rapidity and completeness of the inflammatory response, and the use of adjunctive anti‐fibrotic interventions, must be evaluated.

show abstract

“…The availability of agents that promise immunosuppressive actions that are superior to prednisone and azathioprine and the successes of these agents in animal models and humans with other immune-mediated inflammatory diseases encourage their evaluation in autoimmune hepatitis. [80][81][82] The most promising medications that have emerged to treat or prevent the suboptimal response are ciclosporin, tacrolimus, mycophenolate mofetil (MMF) and budesonide. Rituximab and sirolimus have had more theoretical than actual bases for their consideration, [80][81][82] but they exemplify a period of investigation in autoimmune hepatitis that is responding to clinical need by applying new drugs in small but highly selected clinical situations, and invigorating a call for large formal clinical trials.…”

Section: Alternative Drug Therapies For Suboptimal Responsesmentioning

confidence: 99%

“…[80][81][82] The most promising medications that have emerged to treat or prevent the suboptimal response are ciclosporin, tacrolimus, mycophenolate mofetil (MMF) and budesonide. Rituximab and sirolimus have had more theoretical than actual bases for their consideration, [80][81][82] but they exemplify a period of investigation in autoimmune hepatitis that is responding to clinical need by applying new drugs in small but highly selected clinical situations, and invigorating a call for large formal clinical trials. The nonstandard medications are unlicensed for use in autoimmune hepatitis, and their consideration in this disease has been based on reported experiences in small, single-centre trials.…”

Section: Alternative Drug Therapies For Suboptimal Responsesmentioning

confidence: 99%