Article ; Online: Salvage therapies of autoimmune hepatitis limit proinflammatory immune cells while sparing regulatory T cells.
Hepatology communications
2023 Volume 7, Issue 4
Abstract: Background: Autoimmune hepatitis (AIH) can be clinically controlled by first-line immunosuppressive therapy in the majority of patients. However, a selective decrease in intrahepatic regulatory T cells (Treg) was observed with immunosuppressive therapy, ...
| Abstract | Background: Autoimmune hepatitis (AIH) can be clinically controlled by first-line immunosuppressive therapy in the majority of patients. However, a selective decrease in intrahepatic regulatory T cells (Treg) was observed with immunosuppressive therapy, which was even more pronounced in patients with incomplete responses than in patients who achieved biochemical remission. The effects of salvage therapies on the number of intrahepatic T and B cells, including Treg, are unclear. The hypothesis was that calcineurin inhibitors would further decrease intrahepatic Treg numbers, and the mammalian target of rapamycin inhibitors would increase intrahepatic Treg numbers. Methods: In this retrospective study at 2 centers, CD4+, CD8+ and CD4+FOXP3+ T cells, and CD79a+ B cells were quantified in surveillance biopsies under non-standard-of-care treatment [non-SOC: calcineurin inhibitor (n=10), second-line antimetabolites (n=9), mammalian target of rapamycin inhibitors (n=4)] compared with patients under the standard-of-care treatment (SOC). Results: Intrahepatic T-cell and B-cell counts were not significantly different between patients with biochemical remission under SOC and non-SOC. However, patients with incomplete response under non-SOC had significantly lower liver infiltration with T and B cells, whereas Treg were not reduced compared with SOC. This resulted in an even higher ratio of Treg to T and B cells in non-SOC compared with SOC when biochemical remission was not achieved. The different non-SOC regimens showed no significant difference in liver infiltration with T cells, including Treg and B cells. Conclusions: Non-SOC in AIH partially controls intrahepatic inflammation by limiting the hepatic infiltration of total T and B cells as the main drivers of inflammation without further decreasing intrahepatic Treg. A negative effect of calcineurin inhibitor and a positive effect of mammalian target of rapamycin inhibitors on the number of intrahepatic Treg was not observed. |
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| MeSH term(s) | Humans ; Hepatitis, Autoimmune ; T-Lymphocytes, Regulatory ; Retrospective Studies ; Salvage Therapy ; Calcineurin Inhibitors/pharmacology ; Calcineurin Inhibitors/therapeutic use ; Inflammation ; TOR Serine-Threonine Kinases/pharmacology |
| Chemical Substances | Calcineurin Inhibitors ; TOR Serine-Threonine Kinases (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2023-03-24 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2471-254X |
| ISSN (online) | 2471-254X |
| DOI | 10.1097/HC9.0000000000000088 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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