Table 8.
Emerging Molecular, Cellular and Pharmacological Interventions for Autoimmune Hepatitis
| Emerging interventions | Putative actions | Experience |
|---|---|---|
| Molecular interventions | ||
| CTLA-4Ig (abatacept) | Disrupts CD28 binding to B7 ligands52 | Approved for rheumatoid arthritis52 |
| Dampens T lymphocyte activation34,300 | Improved murine model of PBC303 | |
| Anti-CD20 (rituximab) | Inhibits B lymphocyte activation53,300 | Isolated patients with AIH281–284 |
| Effective in refractory AIH285 | ||
| Anti-TNF-α (infliximab) | Inhibits TNF-α and interferes with maturation of cytotoxic T cells34,52 | Effective in refractory AIH55 |
| Frequent side effects (27%)55 | ||
| Nonmitogenic anti-CD3 | Binds to antigen receptor of T cells300 | Effective in diabetic model307 |
| Promotes apoptosis of immune cells34,53 | Increases insulin in diabetic humans308 | |
| Anti-lysyl oxidase-like 2 (simtuzumab) | Inhibits lysyl oxidase and antifibrotic323 | Phase 2 studies to prevent fibrosis in NAFLD and PSC (https://clinicaltrials.gov) |
| Prevents cross-linkage of collagen322 | ||
| Cellular interventions | ||
| Adoptive transfer of regulatory T cells | Corrects deficiencies in cell population60 | Effective in models of AIH56,312 |
| Expands immune regulatory population60 | Effective in model of PBC313 | |
| Adoptive transfer of mesenchymal stromal cells | Affects innate and adaptive immunity60 | Effective in models of RA301 |
| Inhibits B and T lymphocytes60 | Promising in early human studies319–321 | |
| Modulation of natural killer T cells | Tailored glycolipid antigens skew dual immune actions favorably59,314,315 | Effective in animal models of diabetes, RA, SLE and AIH300,316,317 |
| Pharmacological prospects | ||
| Antioxidants (N-acetylcysteine, S-adenosyl-L methionine) | Reduce reactive oxygen species322,323 | Effective in NAFLD, chronic hepatitis C, and alcoholic cirrhosis324–327 |
| Decrease hepatocyte apoptosis322,323 | ||
| Inhibit stellate cell activation322,323 | ||
| Angiotensin inhibitors (losartan) | Reduce profibrotic transformation of hepatic stellate cells to myofibroblasts322 | Decreased fibrosis in chronic hepatitis C328 |
CTLA-4Ig, cytotoxic T lymphocyte antigen-4 fused with human immunoglobulin; PBC, primary biliary cholangitis; AIH, autoimmune hepatitis; TNF-α, tumor necrosis factor-alpha; NAFLD, nonalcoholic fatty liver disease; PSC, primary sclerosing cholangitis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.