Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs

Selvarajah, Viknesh; Montano‐Loza, Aldo J.; Czaja, Albert J.

doi:10.1111/apt.12042

Cited by 60 publications

(75 citation statements)

References 145 publications

(178 reference statements)

Supporting

Mentioning

Contrasting

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%

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%

Autoimmune hepatitis

Sahebjam

Vierling

2015

Front. Med.

View full text Add to dashboard Cite

show abstract

“…In one study evaluating mycophenolate mofetil in treatment-naïve patients with AIH, 88% of the subjects had biochemical remission in three months. Partial response, corticosteroid withdrawal were observed, respectively, in 12% and 58% of the patients (54) .Drug-related side effects, particularly nauseas, diarrhea and abdominal pain, were noted in 3% to 33% of the patients (4,48,(50)(51)(52)54) . Despite its safety profile and efficacy, it can not be recommend as first-line therapy due to the paucity of data regarding its use and its higher cost in comparison to azathioprine.…”

Section: Management and Treatment Of Aihmentioning

confidence: 98%

“…In these patients, other treatment regimens have been evaluated, including calcineurin inhibitors, either cyclosporin or tacrolimus, mycophenolate mofetil, ursodeoxicholic acid (UDCA), anti-tumor necrosis factor (TNF) alpha agents as well as rituximabe. Some of those agents were also employed in the 10%-15% of subjects, who turn to be intolerant to either azathioprine or corticosteroids, due to the development of side effects (11,13,(48)(49)(50)(51)(52) . There is no evidence-based rational for the use of the aforementioned drugs, currently employed after LT, to treat AIH.…”

Section: Management and Treatment Of Aihmentioning

confidence: 99%

“…Improvement of liver enzymers was observed in 93% of the cases. Only 7% of those treated subjects were refractory or intolerant to cyclosporin (11,13,(48)(49)(50)(51)(52) . One study reported significant improvement in AST and/or ALT with good drug tolerance in 19 (nine treatment naïve) adult patients with AIH followed by 26 weeks.…”

Section: Management and Treatment Of Aihmentioning

confidence: 99%

“…Tacrolimus, on the other hand, have been employed for treatment of AIH since 1995 with improvement in liver enzymes reported in most of the treated patients (13,(48)(49)(50)(51)(52) . Both drugs share similar adverse events, but while diabetes, neurotoxicity, nefrotoxicity, diarrhea, pruritus and alopecia are more frequent with tacrolimus, arterial hypertension, dyslipidemia, hyrsutism and gengival hypertrophy are more commonly seen in cyclosporin-treated patients (48) . In adittion, cyclosporin is generally preferred over tacrolimus due to availability of more data favoring its use in AIH.…”

Section: Management and Treatment Of Aihmentioning

confidence: 99%

See 2 more Smart Citations

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

Bittencourt

Cançado

Couto

et al. 2015

Arq. Gastroenterol.

View full text Add to dashboard Cite

-In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

show abstract

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

et al. 2020

View full text Add to dashboard Cite

US children, 9%-12% (14-16) UK children, 38% (13) Age at presentation Peripubertal and adults Usually under 14 years (153) Mode of presentation Chronic symptoms common Acute onset (~40%) Ascites or GI bleeding rare Acute liver failure possible (555,556) Asymptomatic in 25%-34% Relapse frequent (108) Acute in 25%-75% Acute severe in 2%-6% Laboratory features Hypergammaglobulinemia IgA levels may be reduced (153) Autoantibodies ANA Anti-LKM1 SMA, anti-actin [Anti-LC1, Anti-LKM3] SLA Concurrent immune diseases Autoimmune thyroiditis Autoimmune thyroiditis Rheumatic diseases Diabetes mellitus IBD Vitiligo Autoimmune overlap with PSC (ASC in children) Common in children Rare Atypical pANCA-positive Atypical pANCA-negative Overlap with PBC Seen in adults (not children) Not reported Cirrhosis at presentation Adults, 28%-33% (especially elderly) Rare Children, ≤33% Remission after drug withdrawal Possible Rare, usually need long-term immunosuppression Abbreviations: GI, gastrointestinal; IgA, serum immunoglobulin A. *Removed from marketplace. Abbreviation: anti-PD-L1, antibody to programmed death protein ligand 1. taBle 6. Features of Drug-Induced aIH-like Injury and aIH Clinical Features Drug Induced AIH-Like Injury AIH Gender Mainly women (187) Female predominance, but men also affected (2,384,467) Acute onset Majority (>60%) (231) <20% (2,136) Hypersensitivity (fever, rash, eosinophilia) Up to 30% (231,232,613) Unusual (2,384,467) Temporal relationship with drug Positive (231-234) Negative (2,56,188) HLA DRB1*03:01 or DRB1*04:01 association None (236) Common (29) Concurrent autoimmune diseases Unusual (187) Present in 14%-44% (129,149-152) Cirrhosis at presentation Rare (187) 28%-33% (9,104-107) Management Stop offending drug ± glucocorticoids (187,231,232) Glucocorticoids with AZA (2,384,467) Relapse after drug withdrawal Rare (187) 60%-87% (243,244) Progression to cirrhosis Rare (187) 7%-40% (105) Survival without transplantation 90%-100% (187,232) 10-year survival, 89%-91% (105,451

show abstract

Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs

Cited by 60 publications

References 145 publications

Autoimmune hepatitis

Autoimmune hepatitis

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

Contact Info

Product

Resources

About