Review article: next‐generation transformative advances in the pathogenesis and management of autoimmune hepatitis

Czaja, Albert J.

doi:10.1111/apt.14324

Cited by 22 publications

(12 citation statements)

References 305 publications

(385 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The unmet clinical needs in AIH will drive studies that improve the outcomes of current management, enhance quality of life, prevent disease recurrence, improve management of atypical populations (especially overlap syndromes), and increase understanding of the epidemiology and pathophysiology of AIH through real-world international databases. (528) Pharmacological and biological agents that can restore homeostatic mechanisms that modulate immune responses, (224,(529)(530)(531) reduce oxidative and nitrosative stresses, (532) or inhibit hepatic fibrosis (533) will be evaluated to supplement or replace current treatments ( Table 14). The ability to correct deficient immune cell mediators by the transfer of autologous expanded populations (Tregs, mesenchymal stromal cells, or myeloid-derived suppressor cells) will be another promising investigational front.…”

Section: Future Directions and Unmet Needsmentioning

confidence: 99%

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

Section: Future Directions and Unmet Needsmentioning

confidence: 99%

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

show abstract

“…Autoimmune liver diseases comprise the three major distinct hepatic autoimmune conditions: autoimmune hepatitis (AIHs), sclerosing cholangitis (PSC), and primary biliary cholangitis (formally known as cirrhosis, PBC). To date, several HLA alleles linked to disease risk had been identified by pre‐ and GWAS studies as well as chip‐based genetic analysis …”

Section: The 81 Ah and Aidsmentioning

confidence: 99%

“…To date, several HLA alleles linked to disease risk had been identified by pre-and GWAS studies as well as chip-based genetic analysis. 27 AIHs are chronic self-perpetuating inflammatory diseases, characterized by the presence of specific autoantibody pattern on the basis of which two subtypes of disease are distinguished: type 1 and type 2. Type 1 is characterized by the presence of anti-nucleus antibodies (ANA) and/or antismooth muscle (SMA).…”

Section: Autoimmune Liver Diseases: Autoimmune Hepatitis Sclerosinmentioning

confidence: 99%

Autoimmune diseases and 8.1 ancestral haplotype: An update

Gambino

Aiello

Accardi

et al. 2018

HLA

View full text Add to dashboard Cite

The aim of the present review is to provide an update of the current research into the pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype. This is a common Caucasoid haplotype carried by most people who type for HLA-B8, DR3. Numerous genetic studies reported that individuals with certain HLA alleles have a higher risk of specific autoimmune disorders than those without these alleles. However, much remains to be learned about the heritability of autoimmune conditions. Recently, progress and advances in the field of genome-wide-association studies have revolutionized the capacity to perform large, economically feasible, and statistically robust analyses of HLA within 8.1 ancestral haplotype, and understand its contribute to autoimmune events. In this paper, the characteristic features of this haplotype that might give rise to diverse autoimmune phenotypes are reviewed, focusing on the contribution of the HLA-DRB1 gene, the most polymorphic sequence within the HLA II region.

show abstract

“…Autoimmune hepatitis (AIH) is an incompletely understood inflammatory liver disease that occurs due to loss of tolerance to self‐antigens . It is characterised by its female predominance, raised transaminases, and association with other autoimmune diseases .…”

Section: Introductionmentioning

confidence: 99%

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Nicoll

Roberts

Lim

et al. 2019

Aliment Pharmacol Ther

View full text Add to dashboard Cite

Summary Background Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre‐treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre‐treatment IgG levels.

show abstract

Review article: next‐generation transformative advances in the pathogenesis and management of autoimmune hepatitis

Abstract: Advances in genetics, epigenetics, pathophysiology, epidemiology, and site-directed molecular and cellular interventions constitute the next generation of transformative advances in autoimmune hepatitis.

Cited by 22 publications

References 305 publications

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

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

Autoimmune diseases and 8.1 ancestral haplotype: An update

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Contact Info

Product

Resources

About