Suspicious brush cytology is an indication for liver transplantation evaluation in primary sclerosing cholangitis

Table 1 Histological findings in 30 explanted livers of primary sclerosing cholangitis patients with biliary low-grade dysplasia or high-grade dysplasia/cholangiocarcinoma

	LGD	HGD + CCA2	P value
n	16	14
Early LT1, n	12	11	1.000
Histology intrahepatic
Liver weight, g (IQR)	1380 (1190-1717)	1408 (1262-1487)	0.910
Fibrosis stage 1-4 (IQR)	3.5 (3.0-4.0)	3.0 (2.0-4.0)	0.473
Stage 1-2, n	3	4	0.675
Stage 3-4, n	13	10	0.675
Histology extrahepatic, n
Purulent cholangitis	12	6	0.142
Ulceration	11	6	0.224
Intestinal metaplasia	2	1	0.822
Squamous metaplasia	1	0	0.790

¹In early LTs, suspicion of biliary neoplasia was an important decision criterion for LT;

²CCA four patients; HGD ten patients. Values are median values unless otherwise indicated (IQR). P values: Mann-Whitney U-test for continuous variables, Fisher's exact test for dichotomous variables. CCA: Cholangiocarcinoma; HGD: High-grade dysplasia; IQR: Interquartile range; LGD: Low-grade dysplasia; LT: Liver transplantation.

Table 2 Demographics, laboratory results and endoscopic retrograde cholangiography findings in patients with primary sclerosing cholangitis and low-grade dysplasia, high-grade dysplasia and cholangiocarcinoma

	LGD	HGD	CCA	P value	P value (LGD vs HGD)	P value (HGD vs CCA)	P value (LGD vs CCA)
n	16	10	19	.	.	.	.
Male/female	10/6	8/2	14/5	0.701	.	.	.
Age, yr	32 (26-48)	48 (35-59)	55 (37-60)	0.003	0.056	0.896	0.004
PSC duration, yr	4.1 (2.2-8.3)	4.4 (2.3-7.9)	4.0 (0.3-17.1)	0.948	.	.	.
Symptoms, n	12	8	16	0.890	.	.	.
Icterus, n	2	4	12	0.014	0.483	1.000	0.024
Pruritus, n	9	3	8	1.000	.	.	.
Cholangitis/fever, n	4	2	8	0.415	.	.	.
Fatigue, n	7	3	4	1.000	.	.	.
Pain, n	5	3	4	0.863	.	.	.
MELD score	7.6 (7.4-11.0)	7.6 (6.4-8.7)	7.7 (6.4-10.4)	0.883	.	.	.
IBD, n	10	5	15	0.307	.	.	.
ALP, U/L	175 (90-324)	89 (69-176)	237 (158-396)	0.214	.	.	.
AST, U/L	45 (32-118)	51 (34-64)	59 (38-94)	0.618	.	.	.
ALT, U/L	61 (31-113)	56 (30-102)	55 (46-112)	0.717	.	.	.
Bilirubin, μmol/L	23 (13-32)	11 (8-22)	25 (15-47)	0.354	.	.	.
CA19-9, KU/L	10 (3-22)	10 (5-16)	120 (14-415)	0.002	1.000	0.006	0.006
CEA, μg/L	1.3 (1.0-2.7)	2.4 (1.4-2.9)	2.1 (1.4-5.8)	0.081	.	.	.
mERC score
Intrahepatic (IQR)	6 (4-6)	6 (5-7)	6 (6-6)	0.440	.	.	.
Extrahepatic (IQR)	3 (2-6)	4 (2-6)	4 (2-5)	0.613	.	.	.
Total score (IQR)	9 (7-11)	11 (8-12)	9 (8-11)	0.523	.	.	.

Values are presented as median (IQR) unless otherwise indicated. Jonckeere-Terpstra test was used to analyse differences of continuous variables, and Fisher’s exact test was used for dichotomous variables. Significance values were adjusted using the Bonferroni correction for multiple tests. CCA: Cholangiocarcinoma; HGD: High-grade dysplasia; IQR: Interquartile rate; LGD: Low-grade dysplasia; mERC score: Modified Amsterdam ERC score; MELD score: Model for end-stage liver disease score; IBD: Inflammatory bowel disease; ALP: Alkaline phosphatase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PSC: Primary sclerosing cholangitis; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 3 Brush cytology and DNA flow cytometry in patients with low-grade dysplasia, high-grade dysplasia or cholangiocarcinoma

	LGD	HGD	CCA	P value
Patients, n	16	10	19
Liver transplanted, n	16	10	4
BCs, n (IQR)	4.0 (2.3-5.0)	4.5 (1.8-5.3)	2.5 (1.8-5.3)	0.219
BC suspicious/malignant	11	8	15	0.746
Flow cytometry, n (IQR)	3.0 (2.3-4.0)	3.0 (1.8-5.0)	2.0 (1.0-4.3)	0.195
DNA-index (highest, IQR)	1.0 (1.0-1.2)	1.2 (1.0-1.8)	1.0 (1.0-1.2)	0.745
Aneuploid	6	5	7	0.795

Numbers are median (IQR) or n. P values: Jonckeere-Terpstra test for continuous variables, and Fisher's exact test for dichotomous variables. BC: Brush cytology; CCA: Cholangiocarcinoma; HGD: High-grade dysplasia; IQR: Interquartile rate; LGD: Low-grade dysplasia.