Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review

Table 3 Clinical, imaging, and pathological findings of cases of programmed cell death-1 inhibitor-related sclerosing cholangitis

Case	T-Bil/AST/ALT/ALP/GGT/IgG4	Biliary stenosis /dilation	Hypertrophy of biliary tract	Pathological findings	Treatment (Dosage)	Steroid response
1	Grade 4/NA/Grade 3; Grade 3/Grade 4/NA	NA	NA	Liver: CD8+ T cells infiltration in bile duct	mPSL (1 mg/kg), + UDCA (15 mg/kg)	Moderate
2	0.7/142/144; 1769/902/normal	-/+	Diffuse	Liver: CD8+ and CD4+ T cells infiltration in Glisson’s capsule	PSL (0.5 mg/kg)	Poor
3	3.8/89/101; 1947/804/normal	-/+	Diffuse	NA	PSL (0.5 mg/kg), Biliary drainage	Moderate
4	0.8/108/70; 2996/813/normal	-/+	Diffuse	Liver: CD8+ and CD4+ T cells infiltration in Glisson’s capsule	Biliary drainage	-
5	NA/88/92; 1543/NA/NA	Distal bile duct/+	Diffuse	Bile duct: Interstitial fibrosis, neutrophils infiltration in mucosa	PSL (2 mg/kg) Biliary drainage	Moderate
6	NA/961/1536; 237/2094/NA	NA/-	NA	Liver: Severe steatohepatitis, absence of bile ducts	1st PSL (1 mg/kg), 2nd PSL + UDCA (NA) + MMF (2 g)	Poor
7	NA/NA/>300; >1000/NA/NA	NA	NA	Liver: Degenerative bile duct atypia and periductal fibrosis	1st PSL (1 mg/kg), 2nd PSL + UDCA (NA)	Poor
8	NA/NA/>500; >700/NA/NA	NA	NA	Liver: Attenuated bile duct, cellular and canalicular cholestasis in parenchyma	mPSL (2 mg/kg) + cholestyramine (NA) + MMF (1 g) + UDCA (NA)	Poor
9	0.6/Grade 1/Grade 1; Grade 2/Grade 2/NA	-/+	Diffuse	NA	mPSL (1 mg/kg)	Moderate
10	Normal/129/135; 558/984/NA	Multiple/-	None	Liver: CD8+ T cell infiltration in the periportal zone and cholangitis	mPSL (0.5 mg/kg), + UDCA (10 mg/kg)	Good
11	NA/NA/NA; NA/NA/NA	-/+	Diffuse	Bile duct: Inflammatory cells and lymphocytes infiltration in epithelium	1st PSL (60 mg), 2nd mPSL (500 mg)	Poor
12	NA/58/77; 1111/461/NA	Multiple/+	Diffuse	Bile duct: Destruction of epithelium, fibrosis with CD8+ T cell infiltration in submucosa	Discontinuation of Pembrolizumab	-
13	15.9/454/NA; 5066/NA/20.2	Intrahepatic bile duct/-	Gall bladder	NA	Biliary drainage	-
14	NA/NA/NA; 1065/304/normal	-/+	Diffuse	NA	UDCA (300 mg)	-
15	0.8/69/68; 2427/252/41.0	-/+	NA	Liver: Eosinophil, CD8+, and CD4+ T cell infiltration in the portal tract. Eosinophil infiltration in the epithelial linings of the bile duct	PSL (0.5 mg/kg), + UDCA (NA)	Good
16	Normal/272/516; 615/442/NA	NA	Diffuse	NA	Corticosteroid (NA)	Good
17	3.7/49/31; 598/151/90	-/-	NA	Liver: CD8+ T cells and macrophage infiltration in bile duct	1st PSL (1 mg/kg), 2nd m PSL (1 g), 3rd PSL + MMF (2 g)	Poor
18	1.1/313/296; 2241/868/normal	Intrahepatic bile duct/+	Diffuse	Liver: CD8+ T cell and eosinophil infiltration in the periportal zones, Bile duct: CD8+ T cell infiltration and fibrosis in submucosa	1st UDCA (900 mg) + bezafibrate (400 mg), 2nd m PSL (0.5 g) followed by PSL (1 mg/kg), Biliary drainage	Poor
19	Normal/>100/>100; >900/>500/NA	-/+	NA	Gall bladder: Inflammatory cell infiltration	PSL (0.5 mg/kg) + UDCA (NA), Cholecystectomy	Moderate
20	NA/>100/>300; >800/>1700/normal	-/+	NA	Gall bladder: CD8+ T cell infiltration	PSL (120 mg) + UDCA (NA), Cholecystectomy	Moderate
21	Normal/NA/>100; >400/>1400/NA	NA	NA	NA	PSL (1 mg/kg)	Moderate
22	Normal/52/126; 545/1007/NA	Multiple/+	NA	Liver: CD3+ and CD8 T cell infiltration in the bile duct	PSL (1 mg/kg)	Moderate
23	NA/>300/NA; 793/NA/NA	Multiple/+	Diffuse	Liver: Fibrosis and inflammation in the portal tract, lobular inflammation, mild macrovesicular steatosis	mPSL (NA) following PSL (50 mg), MMF (NA), Tacrolimu (NA)s	Poor
24	0.5/67/68; 2107/279/59	NA/-	Diffuse	Liver: Cholangiopathologic change, CD8/CD4 ratio 12:7, Bile duct: Lymphocyte, eosinophil and plasma cell infiltration	PSL (50 mg)	Moderate
25	1.2/198/233; 1540/332/78	NA/-	Diffuse	Liver: Lobular hepatitis with cholangiopathic change, CD8/CD4 ratio 17:2	PSL (40 mg)	Moderate
26	0.3/91/65; 1683/159/80.4	-/+	Diffuse	Bile duct: Inflammatory cell infiltration	PSL (1 mg/kg) + UDCA (600 mg)	Moderate
27	0.4/245/124; 1245/114/352	-/+	Diffuse	Bile duct: Neutrophil and lymphocyte infiltration	UDCA (600 mg)	-
28	0.6/184/254; 1783/452/128	-/+	Diffuse	Bile duct: Inflammatory cell infiltration	PSL (1 mg/kg) + UDCA (600 mg)	Moderate
29	0.3/64/245; 1328/448/67.3	Intrahepatic bile duct/+	Diffuse	NA	mPSL (2 mg/kg) + MMF (2 g)	Moderate
30	1.3/284/248; 3029/1070/NA	-/+	Diffuse	NA	mPSL (2 mg/kg) + MMF (2 g), Biliary drainage	Moderate
31	0.7/294/85; 4635/829/NA	-/+	Diffuse	Liver: Lymphocyte infiltration in Glisson’s capsule, hydropic degeneration of hepatocytes	mPSL (1.6 mg/kg)	Moderate

T-Bil: Total bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transpeptidase; IgG4: Immunoglobulin G4; mPSL: Methylprednisolone; PSL: Prednisolone; UDCA: Ursodeoxycholic acid; MMF: Mycophenolate mofetil; AZA: Azathioprine; NA: Not available.