Dataset Information

Presence and type of decompensation affects outcomes in autoimmune hepatitis upon treatment with corticosteroids.

ABSTRACT:

Background and aims

Decompensated cirrhosis in autoimmune hepatitis has poor prognosis. Besides liver transplant, treatment for this entity is undefined. We explored the outcomes of autoimmune hepatitis (AIH)-related decompensated cirrhosis with active disease on treatment with steroids.

Methods

In this retrospective analysis, clinical data, laboratory parameters, and prognostic scores, such as baseline model for end-stage liver disease (MELD) scores, were compared among patients of AIH with decompensated cirrhosis with mild/no ascites (n = 38), gross ascites (n = 24), and compensated cirrhosis (n = 32) when administered steroids. The primary outcome was transplant-free survival at 12?months. Biochemical remission rates and other adverse events were also assessed and compared between these groups.

Results

Steroids were initiated at lower doses (25?mg/day-mild/no ascites, 20?mg/day-gross ascites) in patients with decompensated cirrhosis and at 40?mg/day in those with compensated cirrhosis. Transplant-free survival was 25.4%, 74.6%, and 96.9% (P = 0.001), and biochemical remission occurred in 5.1%, 49.0%, and 64.1% (P = 0.001) at 12?months in patients with gross ascites, mild/no ascites, and compensated cirrhosis, respectively. Infections were seen more frequently in decompensated cirrhosis, while other adverse events were comparable. Among decompensated cirrhosis, those with mild/no ascites had better prognostic scores, fewer posttreatment infections, and more frequent biochemical remission than those with gross ascites, achieving rates comparable to compensated cirrhosis. On multivariate analysis, the MELD score (subdistributional hazards ratio [sHR]; 95% confidence interval: 1.153 [1.07-1.24]; P = 0.001) and ascites (sHR: 2.556 [1.565-5.65]; P = 0.020) predicted survival.

Conclusion

Type and severity of decompensation affect outcomes in patients with AIH-related cirrhosis. Those with mild/no ascites have comparable outcomes to those with compensated cirrhosis upon treatment with low-dose steroids.

SUBMITTER: Sharma S

PROVIDER: S-EPMC7812520 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Presence and type of decompensation affects outcomes in autoimmune hepatitis upon treatment with corticosteroids.

Sharma Sanchit S Agarwal Samagra S Kaushal Kanav K Anand Abhinav A Gunjan Deepak D Yadav Rajni R Saraya Anoop A

JGH open : an open access journal of gastroenterology and hepatology 20201113 1

<h4>Background and aims</h4>Decompensated cirrhosis in autoimmune hepatitis has poor prognosis. Besides liver transplant, treatment for this entity is undefined. We explored the outcomes of autoimmune hepatitis (AIH)-related decompensated cirrhosis with active disease on treatment with steroids.<h4>Methods</h4>In this retrospective analysis, clinical data, laboratory parameters, and prognostic scores, such as baseline model for end-stage liver disease (MELD) scores, were compared among patients ...[more]

PMID: 33490617

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Project description:Background & aimsIn autoimmune hepatitis (AIH), the imbalance between regulatory T cells (Tregs) and T-helper type 17 (Th17) cells has been linked to low levels of CD39, an ectoenzyme that hydrolyses ATP, ultimately generating immunosuppressive adenosine. Upregulation of CD39 results from activation of aryl hydrocarbon receptor (AHR), which mediates toxin responses to modulate T-cell immunity. In this study, we investigated whether altered AHR signalling underlies defective CD39 expression and function in AIH Tregs and Th17 cells, therefore contributing to regulatory/effector cell imbalance.MethodsTregs and Th17 cells, obtained from the peripheral blood of 49 patients with AIH and 21 healthy individuals (HI), were tested for response to endogenous and exogenous AHR ligands.ResultsWhen compared to those of HI, AIH-derived Tregs and Th17 cells displayed impaired responses to AHR activation, reflected by impaired upregulation of CD39, delayed increase in ectoenzymatic activity, and defective Treg suppressive function. These impairments resulted, at least in part, from heightened levels of AHRR and Erα in Tregs and high HIF-1α in Th17 cells, and were reverted upon molecular blockade. Importantly, in AIH-derived Tregs, the binding affinity of AHR was higher for Erα than ARNT.ConclusionsIn AIH, high levels of AHRR and HIF-1α inhibit AHR signalling in Tregs and Th17 cells. AHR non-canonical binding to Erα further amplifies the lack of effective CD39 upregulation. Blockade of these inhibitory and/or non-canonical activation pathways represents a potential therapeutic approach to restore CD39 and immunohomeostasis in AIH.Lay summaryIn patients with autoimmune hepatitis, the imbalance between regulatory T cells and T helper type-17 cells is linked to dysfunction of the aryl hydrocarbon receptor pathway, resulting from aberrant inhibition or non-canonical activation. These alterations impair Treg- and Th17 cell-induced upregulation of CD39, an ectoenzyme key to immunoregulation. Blockade of excessive inhibition or non-canonical activation of the aryl hydrocarbon receptor pathway might represent a novel therapeutic strategy to control inflammation while restoring immune balance in autoimmune hepatitis.

Dataset Information

Presence and type of decompensation affects outcomes in autoimmune hepatitis upon treatment with corticosteroids.

Background and aims

Methods

Results

Conclusion

Publications

Presence and type of decompensation affects outcomes in autoimmune hepatitis upon treatment with corticosteroids.

Similar Datasets

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