Table 3.

Histological characteristics of 25 patients with liver-related irAEs

Histological parameters	Hepatitic (n=14)	Cholangio-hepatitic (n=6)	Cholangitic (n=4)
Lobular inflammation
0	2 (14%)	1 (17%)	0 (0%)
1	3 (21%)	5 (83%)	4 (100%)
2	7 (50%)	0 (0%)	0 (0%)
3	2 (14%)	0 (0%)	0 (0%)
Lobular necrosis
0	2 (14%)	2 (33%)	0 (0%)
1	6 (43%)	4 (67%)	4 (100%)
2	6 (43%)	0 (0%)	0 (0%)
3	0 (0%)	0 (0%)	0 (0%)
Centrilobular injury
0	6 (43%)	5 (83%)	4 (100%)
1	5 (36%)	1 (17%)	0 (0%)
2	2 (14%)	0 (0%)	0 (0%)
3	1 (7%)	0 (0%)	0 (0%)
Portal inflammation
0	0 (0%)	0 (0%)	0 (0%)
1	7 (50%)	1 (17%)	1 (25%)
2	4 (29%)	4 (66%)	2 (50%)
3	3 (21%)	1 (17%)	1 (25%)
Interface hepatitis
0	4 (29%)	2 (33%)	0 (0%)
1	6 (43%)	2 (33%)	4 (100%)
2	1 (7%)	2 (33%)	0 (0%)
3	3 (21%)	0 (0%)	0 (0%)
Specific cell subpopulations Plasma cells
0	5 (36%)	2 (33%)	1 (25%)
1	8 (57%)	4 (66%)	3 (75%)
2	1 (7%)	0 (0%)	0 (0%)
3	0 (0%)	0 (0%)	0 (0%)
Eosinophils
0	5 (36%)	1 (17%)	1 (25%)
1	4 (29%)	4 (66%)	2 (50%)
2	5 (36%)	1 (17%)	1 (25%)
Neutrophils
0	3 (21%)	0 (0%)	0 (0%)
1	9 (64%)	2 (33%)	1 (25%)
2	2 (14%)	4 (67%)	3 (75%)
Biliary abnormalities Bile duct injury
0	8 (57%)	0 (0%)	0 (0%)
1	6 (43%)	6 (100%)	4 (100%)
Ductular reaction
0	3 (21%)	0 (0%)	0 (0%)
1	8 (57%)	0 (0%)	0 (0%)
2	3 (21%)	5 (83%)	3 (75%)
3	0 (0%)	1 (17%)	1 (25%)
Biliary metaplasia
0	11 (79%)	1 (17%)	2 (50%)
1	3 (21%)	3 (50%)	0 (0%)
2	0 (0%)	1 (17%)	1 (25%)
3	0 (0%)	1 (17%)	1 (25%)
Granulomas
0	4 (29%)	6 (100%)	1 (25%)
1	7 (50%)	0 (0%)	3 (75%)
2	3 (21%)	0 (0%)	0 (0%)
Fibrosis
F0	4 (29%)	0 (0%)	0 (0%)
F1	9 (64%)	3 (50%)	3 (75%)
F2	1 (7%)	2 (33%)	0 (0%)
F2/F3	0 (0%)	1 (17%)	1 (25%)
CD4+/CD8+ ratio	12	6	4
≤1	10 (83%)	4 (66%)	2 (50%)
>1	2 (17%)	2 (33%)	2 (50%)

One patient had only macrovesicular steatosis at the biopsy and could not be included in either of the immune-related hepatitis, cholangitis or cholangiohepatitis classes. Classification is based on the description of histological features in online supplemental table 4.

irAEs, immune-related adverse events.