Researchers have identified biomarkers that could help predict the outcome of liver transplantation in children with end-stage diseases such as Alagille syndrome (ALGS).
They said their findings could also be important in predicting the efficacy of immunosuppressive therapy following liver transplantation in children and “might pave the way to improved therapeutic options.”
The team aimed to characterize the role of soluble and cellular immune mediators during the first year after pediatric liver transplantation and to identify the immunological biomarkers of major end-stage diseases including ALGS before and after pediatric liver transplantation. They also wanted to establish the best immunosuppressive regimen at various stages after transplantation.
The researchers measured 50 cytokines, chemokines, growth factors, and adhesion factors in the plasma of the transplant recipients before and up to 1 year after the operation. They also quantified the absolute cell counts and relative proportions of major immune populations in the blood.
Read more about the treatment of Alagille syndrome
They found the highest count of lymphoid and myeloid immune cells like CD3+ T cells, CD19+ B cells, CD56+ natural killer (NK) cells, granulocytes, and monocytes in patients with ALGS. The plasma concentrations of C-X-C motif chemokine ligand (CXCL) 10, C-C motif chemokine ligand (CCL) 4, platelet-derived growth factor (PDGF)-b, fibroblast growth factor (FGF), and interleukin (IL)-9/13 were also higher in these patients.
The main changes in the plasma secretome occurred by day 21 following transplant in all patients. For example, proinflammatory CXCL8/9/10/12, CCL7, and IL-17 mediators were absent, and the levels of liver enzymes such as alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase were reduced, as were rejection rates. Therefore, these could be predictive of a better outcome following transplantation, according to the researchers.
The results also showed that the absolute counts and proportions of myeloid cells peaked at day 7 after transplant and then gradually decreased.
On the contrary, the number of CD3+ T cells and CD56+ NK cells were reduced by day 7 but recovered by day 21, and they continued to increase for 12 months.
The researchers also reported that “some cellular immune patterns were linked to reduced inflammation and improved liver parameters.”
“Cellular and soluble blood secretome signatures might act as biomarkers for potential outcome” after pediatric liver transplantation, they concluded.
In terms of immunosuppression after transplantation, the most efficient downregulation of proinflammatory immune mediators and lower rejection rates were achieved with a combination of tacrolimus and mycophenolate or tacrolimus and steroids. Tacrolimus plus mycophenolate was better at reducing liver enzymes, especially in boys, while tacrolimus plus steroids was better at improving bilirubin levels. Using all 3 medications together did not lead to any improvement and instead reduced the beneficial effects of the 2 combinations.
These findings were presented at the 54th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).
There are some medications that can help control the symptoms of ALGS. However, in some cases, these are not effective enough, and around 21% to 31% of patients end up requiring liver transplantation.
Chichelnitskiy E, Ruhl L, Goldschmidt I, et al. Characterization of the longitudinal dynamics of soluble and cellular immune mediators in pediatric liver transplantation (pLTx) identified cytokine/chemokine signatures potentially linked to beneficial immunosuppressive regimes (IS) and recovery. Abstract presented at: 54th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); June 22-25, 2022; Copenhagen, Denmark.