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Corticosteroids, Immunomodulators Help Prevent Liver Transplant in Pediatric Autoimmune Hepatitis

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A new review and analysis suggests a combination treatment regimen for children in acute liver failure due to autoimmune hepatitis may help them maintain native liver survival.

Corticosteroids, Immunomodulators Help Prevent Liver Transplant in Pediatric Autoimmune Hepatitis

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A new systematic review and meta-analysis supports the use of immunosuppressive therapy to achieve native liver survival in children presenting with autoimmune hepatitis in acute liver failure cases.

The new data, presented at the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) 2023 Annual Meeting in San Diego this week, showed a combination treatment of corticosteroids and immunomodulators are associated with improved rates of native liver survival among pediatric patients in acute liver failure due to autoimmune hepatitis. The findings may provide clinicians a clearer guide to interventional strategies that ultimately prevent the need for liver transplant in younger patients.

Investigators led by Harry Sutton, MD, of the division of gastroenterology, hepatology and nutrition at the Toronto Hospital for Sick Children, sought to better characterize and interpret the management strategies for and outcomes of pediatric patients with autoimmune hepatitis presenting in acute liver failure—a section of hepatic research that which currently lacks large cohort analysis data.

“Autoimmune hepatitis in children has diverse presentations, however when presenting in acute liver failure it can be fatal and often requires liver transplantation,” investigators wrote. “Liver transplant may be avoided with immunosuppressive therapy.”

Sutton and colleagues conducted their systematic review using data from clinical trials available on PubMed and Embase, published between 2000 - 2020. Eligible trials for their analysis included pediatric and adolescent patients aged <21 years old with diagnosed type 1 or 2 autoimmune hepatitis, defined by serum immunoglobulin levels, autoantibodies and liver histopathology.

The team excluded trials wherein patients had positive hepatitis A - E serology; an evidence of drug-induced liver injury; MDR3 deficiency or Wilson disease; history with corticosteroid or non-steroid immunomodulator therapy; or were treated in instances when liver transplant was not readily available at the reporting clinic.

Investigators sought individual patient-level data interpreting clinical and biochemical characteristics, prescribed therapies, and clinical outcomes of disease.

Their final analysis included 325 patients across 61 identified studies plus 5 patients with relevant clinical criteria from their own research institution. Median patient age was 10 years old (range, 6 - 14) and two-thirds (67%) were female. Patients with type 2 autoimmune hepatitis were significantly younger at presentation compared to their type 1 disease peers (6.9 vs 11.0 years; P =.044).

Regarding treatment outcomes, 3 in 5 (n = 197 [60%]) patients achieved native liver survival. Another 35% (n = 116) underwent liver transplant; 5% (n = 17) died during the assessment. Sutton and colleagues observed a 2.5-fold increased likelihood of pediatric patients with autoimmune hepatitis-associated acute liver failure achieving native liver survival when treated with corticosteroids plus a non-steroid immunomodulator (odds ratio [OR], 2.5; 95% CI, 1.3 - 5.1; P = .008).

Investigators additionally observed a 3.3-fold increased risk of either liver transplant or death among patients with type 2 autoimmune hepatitis versus those with type 1 (95% CI, 1.1 - 10.0; P =.03).

The team noted their findings are limited by the retrospective nature of the review and analysis. Nonetheless, they concluded that children presenting for the first time with autoimmune hepatitis in acute liver failure have a significantly improved likelihood of native liver survival when receiving combination corticosteroids and immunosuppressive treatment.

“These data offer hope for native liver survival in autoimmune hepatitis-acute liver failure and suggest a need to identify biomarkers that predict which children require combination immunosuppressants in order to avoid liver transplants,” they wrote.

References

Sutton H, Fawzy A, Vandriel S, Sonnenberg M, et al. Management and Outcomes in Children with Autoimmune Hepatitis Presenting in Acute Liver Failure: An Individual Patient Data Meta-Analysis. Paper presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2023 Annual Meeting; October 4 - 7; San Diego, CA. Accessed October 4, 2023.

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