Table 4.
Recurrence rate of CHILI.
| Recurrence n = 12 (23.5%) | No recurrence n = 39 (76.5%) | p value | |
|---|---|---|---|
| Baseline characteristics | |||
| Age (years), mean (SD) | 63.8 (14.2) | 60.3 (16.5) | 0.523 |
| Sex, n (%) | 0.089 | ||
| Female | 8 (17.4) | 13 (28.3) | |
| Male | 4 (8.7) | 21 (45.7) | |
| Pre-existing liver disease, n (%) | |||
| Liver metastasis | 0 | 5 (10.9) | 0.159 |
| Cirrhosis | 0 | 1 (2.2) | 0.548 |
| Cancer, n (%) | 0.574 |
||
| Lung | 4 (8.7) | 9 (19.6) | |
| Melanoma | 4 (8.7) | 17 (37) | |
| Renal and urothelial | 1 (2.2) | 5 (10.9) | |
| Other cancer |
2 (4.3) |
3 (6.5) |
|
| Previous CHILI characteristics | |||
| Checkpoint inhibitor, n (%) | 0.514 | ||
| Anti-PD-1/PDL-1 | 8 (17.4) | 19 (41.3) | |
| Combination therapy with anti-CTLA-4 | 4 (8.7) | 15 (32.6) | |
| Cycles of ICI infusion, mean (SD) | 3.9 (2.8) | 4.3 (5.7) | 0.827 |
| Time until onset (days), mean (SD) | 156.8 (179.3) | 129.4 (218.7) | 0.699 |
| Autoantibodies | |||
| ANA only | 3 (6.5) | 6 (13) | 0.581 |
| ASMA | 0 | 2 (4.3) | 0.390 |
| Pattern, n (%) | 0.651 | ||
| Cholestatic | 4 (8.7) | 11 (23.9) | |
| Mixed | 5 (10.9) | 10 (21.7) | |
| Hepatocellular | 3 (6.5) | 13 (28.3) | |
| Severity (CTCAE), n (%) | 0.830 | ||
| Grade 1 | 0 | 1 (2.2) | |
| Grade 2 | 2 (4.3) | 8 (17.4) | |
| Grade 3 | 9 (19.6) | 21 (45.7) | |
| Grade 4 | 1 (2.2) | 4 (8.7) | |
| Bile duct injury, n (%) | 2 (4.3) | 1 (2.2) | 0.098 |
| Liver biopsy, n (%) | 4 (8.7) | 9 (19.6) | 0.650 |
| Histology, n (%) | |||
| Biliary injury | 4 (30.8) | 2 (15.4) | 0.009 |
| Granuloma | 1 (7.7) | 4 (30.8) | 0.713 |
| Endothelitis | 1 (7.7) | 0 | 0.118 |
| Fibrin ring granuloma | 0 | 1 (7.7) | 0.488 |
| Treatment, n (%) | |||
| Corticoids only | 6 (13) | 20 (43.5) | 0.553 |
| UDCA only | 1 (2.2) | 3 (6.5) | 0.553 |
| Corticoids + UDCA | 2 (4.3) | 8 (17.4) | 0.553 |
| Corticoid-including regimen | 8 (17.4) | 28 (60.9) | 0.257 |
| No treatment | 3 (6.5) | 3 (6.5) | 0.153 |
| Other immunosuppressant | 0 | 5 (10.9) | 0.159 |
| Initial dose of corticoids (mg/day), mean (SD) |
666.7 (288.7) |
805.6 (242.9) |
0.429 |
| Characteristics at ICI rechallenge | |||
| Same checkpoint inhibitor, n (%) | 9 (19.6) | 18 (39.1) | 0.182 |
| Checkpoint inhibitor at rechallenge, n (%) | 0.258 | ||
| Anti-PD-1 | 10 (21.7) | 33 (71.8) | |
| Anti-PDL-1 | 0 | 1 (2.2) | |
| Anti-PD-1 + anti-CTLA-4 | 1 (2.2) | 1 (2.2) | |
| Simultaneous treatment, n (%) | 7 (17.5) | 28 (70) | 0.316 |
| Cancer status (RECIST 1.1), n (%) | 0.570 | ||
| Progressive disease | 2 (4.3) | 11 (23.9) | |
| Stable disease | 3 (6.5) | 3 (6.5) | |
| Partial response | 5 (10.9) | 12 (26.1) | |
| Complete response | 1 (2.2) | 5 (10.9) | |
| Other irAEs, n (%) | 1 (8.3) | 0 | 0.640 |
Data are expressed as mean (SD).
The Chi-square test was used for comparison between qualitative variables, and ANOVA and Student’s t test were used for quantitative variables.
Levels of significance: p <0.05. ANA, N <1/160; ASMA, N <1/40.
ANA, antinuclear antibodies; ASMA, antismooth muscle antibodies; CHILI, checkpoint inhibitor-induced liver injury; CTCAE, Common Terminology Criteria for Adverse Events; CTLA-4, cytotoxic T-lymphocyte-associated protein-4; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; PD-1, programmed cell death-1; PDL-1, programmed cell death ligand-1; RECIST 1.1, Response Evaluation Criteria in Solid Tumours 1.1; UDCA, ursodeoxycholic acid.