Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis

Table 1 Seven-feature, 15-point histological scoring system devised for the interpretation of liver biopsy materials in neonatal cholestasis¹

Parameter	Histological characterization	Histological grade
Portal ductal proliferation	None	0
	Mild	1
	Moderate	2
	Marked	3
Bile plug in portal ductules	Absent	0
	Present	2
Porto-portal bridging	None	0
	< 50% of portal tracts	1
	> 50% of portal tracts	2
Lymphocytic infiltrate in portal region	None	2
	Mild	1
	Moderate/severe	0
Multinucleated hepatocytes	None	2
	Only around central vein	1
	Diffuse	0
Neutrophils in the infiltrate	Absent or mild	1
	Moderate or marked	0
Hepatocellular swelling	None	2
	Mild/focal	1
	Periportal/diffuse	0

¹The higher the score, the more likely to be biliary atresia.

Table 2 Characteristics of 83 liver biopsy specimens obtained from 78 patients with neonatal cholestasis

	Biliary atresia (n = 33)	Intra-hepatic cholestasis (n = 50)	All (n = 83)
Age at biopsy (d)
Median (range)	65 (34-371)	62 (26-180)	63 (26-371)
Route of biopsy
Percutaneous	16	37	53
Operative	17	13	30
Number of portal tracts
< 5	4	20	24
≥ 5	29	30	59

Table 3 Diagnostic accuracy of hepatic histology in patients with neonatal cholestasis-author’s personal interpretation

	Author’s histological diagnoses
	Biliary atresia	Neonatal hepatitis	Paucity bile	Final clinical diagnosis ducts
Biliary atresia	33	30	3
Idiopathic neonatal hepatitis	35	2	33
Cytomegalovirus hepatitis	6	3	3
PFIC	4	1	3
Alagille syndrome	1			1
Parenteral nutrition-associated cholestasis	1		1
Congenital hypothyroidism	1	1
Caroli disease	1		1
Severe asphyxia	1		1
Total	83	37	45	1

PFIC: Progressive familial intrahepatic cholestasis; Sensitivity: TP/(TP + FN) = 30/(30 + 4) = 91%; Specificity = TN/(TN + FP) = 43/(43 + 7) = 86%; Diagnostic accuracy = (TP + TN)/(TP + TN + FN + FP) = (30 + 43)/83 = 88%.

Table 4 Clinical and histological characteristics of 3 patients with biliary atresia diagnosed histologically as neonatal hepatitis by the author

Patient	Bilirubin total/conj. (μmol/L)	γGT (IU/L)	RHBS	Liver biopsy			Reasons for exploratory laparotomy
				Days	Route	Major histological findings
NKC	154/120	179	Non-excretory	34	Percutaneous	Inadequate number of portal tracts. No portal bile duct and pale stools proliferation. Hepatocytic degeneration and swelling, occasional giant cells formation	Persistent jaundice
SQ	189/153	442	Non-excretory	45	Percutaneous	Biopsy material fragmented. Giant cells transformation and pale stools. Intra-hepatocytic cholestasis and bile plug formation	Persistent jaundice
LQY	124/109	144	Non-excretory	78	Operative	Mild ductular proliferation and lymphocytic infiltration of portal tracts

conj.: Conjugated; γGT: γ glutamyl transferase; RHBS: Radionuclide hepatobiliary scintigraphic study.

Table 5 Histological features of biliary atresia and other intrahepatic cholestasis (n)

Histological features	Biliary atresia	Intrahepatic cholestasis1
Ductular proliferation
None	1	31
Mild	2	11
Moderate	3	4
Severe	27	2
Bile plug in bile ductules
Absent	10	42
Present	21	7
Porto-portal bridging
None	1	33
< 50% of portal tracts	8	6
> 50% of portal tracts	22	6
Lymphocytic infiltration
Moderate to severe	7	23
Mild	16	24
Absent or mild	10	3
Neutrophilic infiltration
Moderate to severe	3	15
Absent to mild	30	35
Giant cell transformation of hepatocytes
Diffuse	1	16
Only around central vein	13	23
None	19	11
Hepatocytes swelling
Hepatocytes swelling	4	27
Mild/focal	13	22
None	16	1

¹Including cytomegalovirus hepatitis (n = 6), progressive familial intrahepatic cholestasis (n = 4), Alagille syndrome (n = 1), TPN-associated cholestasis (n = 1), hypothyroidism (n = 1), Caroli disease (n = 1), severe perinatal asphyxia (n = 1), idiopathic neonatal hepatitis (n = 35).

Table 6 Sensitivity, specificity, positive and negative predictive values of various histological features in differentiating biliary atresia from non-BA

Histological features	BA	Non-BA	Sensitivity for BA (%)	Specificity for BA (%)	Positive PV for BA & negative PV for non-BA (%)	Negative PV for BA & positive PV for non-BA (%)
Bile ductular proliferation
Moderate or severe	30	6	30/33 (91)	30/33 (91)	30/36 (83)	42/45 (93)
None or mild	3	42
Bile plug in bile ductules
Present	21	7	21/31 (68)	42/49 (86)	21/28 (75)	42/52 (81)
Absent	10	42
Porto-portal bridging
> 50% of portal tracts	22	6	22/31 (71)	39/45 (87)	22/28 (79)	39/48 (81)
None/< 50% of portal tracts	9	39

PV: Predictive value; BA: Biliary atresia.

Table 7 Sensitivity, specificity, positive and negative predictive values of various histological features in differentiating non-biliary atresia from biliary atresia

Histological features	Non-BA	BA	Sensitivity for BA (%)	Specificity for BA (%)	Positive PV for non-BA & negative PV for BA (%)	Negative PV for non-BA & positive PV for BA (%)
Lymphocytic infiltration
Moderate to severe	23	7	23/50 (46)	26/33 (79)	23/30 (77)	26/53 (49)
Absent or mild	27	26
Neutrophilic infiltration
Moderate to severe	15	3	15/50 (30)	30/33 (91)	15/18 (83)	30/65 (46)
Absent to mild	35	30
Giant cell transformation of hepatocytes
Diffuse	16	1	16/50 (32)	32/33 (97)	16/17 (94)	32/66 (48)
None or around central vein	34	32
Hepatocytes swelling
Periportal or diffuse	27	4	27/50 (54)	29/33 (88)	27/31 (87)	29/52 (56)
None or mild/focal	23	29

Table 8 Total histological score according to underlying diagnosis

Total score	Biliary atresia	Non-biliary atresia
0	0	3
1	0	6
2	1	6
3	0	11
4	2	10
5	0	8
6	1	0
7	0	3
8	4	0
9	3	1
10	4	1
11	3	0
12	4	0
13	7	1
14	4	0
< 6	4	44
≥ 6	29	7
< 7	4	47
≥ 7	29	3
< 8	8	47
≥ 8	25	3
Total	33	50

Table 9 A summary of the results and a comparison with the histological diagnosis made by reporting pathologists

Parameters	Sensitivity	Specificity	Diagnostic accuracy
Author’s own interpretation-without scoring system	91	86	88
Author’s own interpretation-with scoring system	88	94	92
Pathologists’ diagnosis	82	80	81