Table 3 Summary of the postulated upstream pathogenetic processes in primary biliary cirrhosis and their characteristics.
| Category | Mechanism/process/factor | Observation confirmed in repeat studies | Mechanism observed in majority of PBC patients | Mechanism able to explain post‐transplant disease recurrence across HLA boundaries | Mechanism able to explain tissue tropism of PBC |
|---|---|---|---|---|---|
| Immunological | AMA | Yes | Yes | Yes (ADCC) | No |
| ANA | Yes | No | ? (BEC surface expression not reported) | No | |
| AMA transcytosis | Yes | ? | Yes | Yes | |
| CD4 T‐cell response to PDC | Yes | Yes | No | ? | |
| CD8 T‐cell response to PDC | Yes | Yes | No | ? | |
| T‐cell response to nuclear antigen | No data yet | ? | No | ? | |
| ? TGFβ‐driven EMT | No | ? | Yes | ? | |
| Non‐immunological | Retrovirus | No | ? | Yes | Yes |
| Environmental toxin effect | Yes | ? | Yes | Yes | |
| Acclelerated BEC senescence | No | ? | Yes | Yes | |
| Oxidative stress | Yes | ? | Yes | Yes |
ADCC, antibody‐directed cell cytotoxicity; AMA, antimitochondrial antibody; ANA, antinuclear antibody; BEC, biliary epithelial cell; EMT, epithelial to mesenchymal transition; HLA, human leukocyte antigen; PBC, primary biliary cirrhosis; PDC, pyruvate dehydrogenase complex; TGFβ, transforming growth factor beta.
? Denotes the fact that this aspect of the process has not been studied in large enough study cohorts and/or that the appropriate mechanistic studies have not been performed.