Management of patients with difficult autoimmune hepatitis

Parker, Richard; Oo, Ye Htun; Adams, David H.

doi:10.1177/1756283x12450251

Cited by 17 publications

(9 citation statements)

References 109 publications

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“…Second-line therapies have been used to manage treatment failure, incomplete response, and drug intolerance (402,403) (see definitions in Table 2). Treatment failure occurs in 7%-9% of adults and is associated with increased risk of progression to cirrhosis and liver failure, with mortality rates as high as 30%.…”

Section: Second-line Treatmentsmentioning

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

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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

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Section: Second-line Treatmentsmentioning

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

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“…Moreover, histological patterns typically associated with AIH have also been observed in patients with DILI, further complicating the differentiation between the two entities . The finding of cirrhosis at presentation and subsequent signs of chronicity favour the diagnosis of AIH.…”

Section: Introductionmentioning

confidence: 99%

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Weber¹,

Benesic²,

Rotter³

et al. 2019

Liver International

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Background Drug‐induced liver injury (DILI) and idiopathic autoimmune hepatitis (AIH) are competing diagnoses in patients with acute liver injury (ALI) and drug intake. In absence of unequivocal markers, scores like RUCAM and AIH are used to distinguish both entities. However, in some cases the diagnosis remains ambiguous. Our aim was to identify a simple parameter to discriminate DILI and AIH shortly after starting corticosteroid treatment. Methods For the current analysis, 44 patients with ALI who took at least one drug and who received corticosteroids were included and comprised 22 DILI and 22 AIH cases. Scores of AIH and RUCAM were calculated at initial presentation, the final diagnosis was made from analysing the course of disease. Changes in the serum alanine aminotransferase (ALT) concentrations after starting corticosteroid treatment were determined and compared between the DILI and AIH groups. Results Fifty‐nine per cent of patients (n = 26) were correctly classified at presentation by AIH score and RUCAM respectively. However, in one‐third (n = 13) of the 44 patients, results were inconclusive and five other patients were misclassified. The decrease in ALT levels 1 week after the initiation of steroid therapy was significantly more pronounced in patients with the final diagnosis of DILI than in AIH patients (accuracy 77%). This difference was also observed in the 18 initially misclassified or inconclusive cases (accuracy 83%). Conclusion Short‐term response of ALT to corticosteroid therapy helps to differentiate DILI and AIH. This finding may be helpful in treatment decision for patients with inconclusive diagnostic scores.

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“…Partial response in AIH is defined as the incomplete decline of transaminases and/or IgG/γ-globulines under treatment. In these patients, a step-up approach seems reasonable (reviewed in [2] ). First, alternative or additional diagnoses have to be taken into consideration.…”

Section: Insufficient Response To Standard Treatmentmentioning

confidence: 99%

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

Sebode¹,

Schramm²

2015

Dig Dis

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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.

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Management of patients with difficult autoimmune hepatitis

Cited by 17 publications

References 109 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

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

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

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