Table 1.
Clinical characteristics of the patients with IMC of three types induced by ICIs
| Characteristics | All patients (n = 53) | Small-ducts type (n = 12) | Large-ducts type (n = 29) | Mixed type (n = 12) | P value |
|---|---|---|---|---|---|
| Sex, men (%) | 35 (66.0%) | 8 (66.7%) | 17 (58.6%) | 10 (83.3%) | 0.318 |
| Age, median (range, year) | 68 (43–89) | 64.5 (43–83) | 68.5 (50–89) | 67.5 (43–80) | 0.704 |
| Primary cancer type | 0.068 | ||||
| Lung caner | 37 | 5 | 23 | 9 | |
| Melanoma | 7 | 4 | 2 | 1 | |
| Gastric caner | 4 | 1 | 1 | 2 | |
| Bladder cancer | 2 | 0 | 2 | 0 | |
| Other cancers | 3 | 2 | 1 | 0 | |
| ICIs type | 0.577 | ||||
| Nivolumab | 28 | 4 | 17 | 7 | |
| Pembrolizumab | 19 | 6 | 9 | 4 | |
| Atezolizumab | 2 | 1 | 1 | 0 | |
| Avelumab | 1 | 0 | 1 | 0 | |
| Ipilimumab | 1 | 1 | 0 | 0 | |
| Nivolumab + Ipilimumab | 1 | 0 | 0 | 1 | |
| Durvalumab + tremelimumab | 1 | 0 | 1 | 0 | |
| ICIs cycles until onset, median (range) | 5 (1–27) | 2.5 (1–13) | 7 (1–25) | 5 (3–27) | 0.025†; 0.027‡ |
| Biochemical parameters | |||||
| ALP, median (range, IU/L) | 1328 (237–4635) | 678 (237–2837) | 1683 (550–4635) | 1652 (545–2427) | 0.025†; 0.021‡ |
| ALT, median (range, IU/L) | 156 (31–1536) | 217 (31–1536) | 101 (45–516) | 162 (68–331) | 0.105 |
| Pathological findings | |||||
| Small-ducts cholangitis | 24 | 12 | - | 12 | |
| Portal inflammation, n (%) | 21 (87.5%) | 10 (83.3%) | - | 11 (91.7%) | 1.000 |
| Bile duct injury, n (%) | 24 (100%) | 12 (100%) | - | 12 (100%) | - |
| Ductular reaction, n (%) | 13 (54.2%) | 5 (41.7%) | - | 8 (66.7%) | 0.401 |
| Bile duct loss, n (%) | 4 (16.7%) | 3 (25%) | - | 1 (8.3%) | 0.590 |
| Cholestasis, n (%) | 7 (29.2%) | 5 (41.7%) | - | 2 (16.7%) | 0.371 |
| Large-ducts cholangitis | 9 | - | 7 | 2 | |
| Inflammatory infiltration | 9 (100%) | - | 7 (100%) | 2 (100%) | - |
| Noncentricular diffuse fibrosis | 3 (33.3%) | - | 1 (14.3%) | 2 (100%) | 0.083 |
| Imaging of large bile ducts | 38 | 26 | 12 | ||
| Intrahepatic bile ducts | 5 (13.2%) | - | 1 (3.8%) | 4 (33.3%) | 0.027§ |
| Extrahepatic bile duct | 15 (39.5%) | - | 14 (53.8%) | 1 (8.3%) | 0.012§ |
| Intra- and extrahepatic bile duct | 18 (47.4%) | - | 11 (42.3%) | 7 (58.3%) | 0.489 |
| Treatment | |||||
| Without immunosuppression therapy | 5 | 0 | 5 | 0 | - |
| GC monotherapy | 32 | 6 | 18 | 8 | - |
| GC + MMF | 8 | 3 | 4 | 1 | - |
| GC + AZA | 2 | 0 | 1 | 1 | - |
| GC + MMF + TAC | 1 | 0 | 0 | 1 | - |
| GC + TCZ | 3 | 2 | 0 | 1 | - |
| GC + MMF + TAC + TCZ | 1 | 0 | 1 | 0 | - |
| GC + MMF + plasmapheresis | 1 | 1 | 0 | 0 | - |
| UDCA | 20 | 6 | 9 | 5 | - |
| Response to immunosuppressive therapy | |||||
| Biochemical response | 47 | 12 | 23 | 12 | |
| Complete response | 4 (8.5%) | 1 (8.3%) | 2 (8.7%) | 1 (8.3%) | 1.000 |
| Partial response | 33 (70.2%) | 8 (66.7%) | 18 (78.3%) | 7 (58.3%) | 0.505 |
| Poor response | 10 (21.3%) | 3 (25%) | 3 (13.0%) | 4 (33.3%) | 0.277 |
| Imaging response | 6 | - | 6 | NA | |
| Improve / worsen | 4/2 | - | 4/2 | NA | - |
| Histological response | 4 | 2 | 1 | 1 | |
| Reduced inflammation | 4 | 2 | 1 | 1 | - |
| Progressive bile duct injury | 2 | 2 | 0 | 0 | - |
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AZA, azathioprine; GC, glucocorticoid; ICIs, immune checkpoint inhibitors; IMC, immune-mediated cholangitis; MMF, mycophenolate mofetil; NA, unavailable; UDCA, ursodeoxycholic acid.
†P < 0.05 among the three types
‡P < 0.05 small-ducts type vs. large-ducts type
§P < 0.05 large-ducts type vs. mixed type.