Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology

doi:10.4254/wjh.v16.i12.1407

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Hepatol. Dec 27, 2024; 16(12): 1407-1416
Published online Dec 27, 2024. doi: 10.4254/wjh.v16.i12.1407

Table 1 Comprehensive diagnosis score system for autoimmune hepatitis (1999)

Parameters/clinical characteristics	Scoring	Parameters/clinical characteristics	Scoring
Women	+2	Drug history
Ratio of ALP (normal upper limit multiple) to AST (or ALT) (normal upper limit multiple)		Positive	-4
< 1.5	+2	Negative	+1
1.5-3.0	0	Average alcohol intake (g/d)
> 3.0	-1	< 25	+2
Serum γ-Ratio of globulin or IgG to normal value		> 60	-2
> 2.0	+3	Histological examination of the liver
1.5-2.0	+2	Interfacial hepatitis	+3
1.0-1.5	+1	Mainly lymphocyte-plasma cells	+1
< 1.0	0	Hepatocytes showed rosette-like changes	+1
ANA, ASMA or LKM-1 titer		No such manifestations	-5
> 1:80	+3	Bile duct alterations	-3
1:80	+2	Other changes	-3
1:40	+1	Other immune diseases	+2
< 1:40	0	Other available parameters
AMA positive	-4	Other specific autoantibodies (SLA/LP, LC-1, ASGPR, pANCA) are positive	+2
Hepatitis virus markers		HLA-DR3 or DR4	+1
Positive	-3	Response to treatment
Negative	+3	Completely; recurrence	+2; +3
Interpretation of total points
Before treatment		Before treatment
Clear AIH	≥ 16	Clear AIH	≥ 18
Possible AIH	10-15	Possible AIH	12-17

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; ANA: Antinuclear antibody; AMA: Anti-mitochondrial antibody; ASMA: Anti-smooth muscle antibody; LKM-1: Anti-liver-kidney microsome type 1; AIH: Autoimmune hepatitis.

Table 2 Simplified diagnosis of autoimmune hepatitis by the international autoimmune hepatitis group

Variables	Criteria	Score	Remarks
ANA or SMA	≥ 1:40	1	It is equivalent to the lowest titer of ANA 1:100 commonly used in China
ANA or SMA	≥ 1:80	2	Maximum 2 points when multiple items appear at the same time
LKM-1	≥ 1:40	2
SLA	Positive	2
IgG	> upper limit of normal value. > 1.1 times the upper limit of normal value	1; 2
Liver histology	AIH compliant. Typical AIH manifestations	1; 2	Interfacial hepatitis, lymphocyte-plasma cells infiltration in the confluent zone and lobules, rosettes of hepatocytes, and penetration are considered to be characteristic hepatic histologic changes, with three of the four being typical
Excluding viral hepatitis	Yes	2
= 6 points: Suspected AIH ≥ 7 points: Confirmed AIH

ANA: Antinuclear antibody; SMA: Smooth muscle antibodies; LKM-1: Anti-liver-kidney microsome type 1; SLA: Anti-soluble liver antigen; AIH: Autoimmune hepatitis.

Table 3 Comparison of biochemical indexes among the three groups

	NAFL (n = 36)	NASH (n = 51)	Cirrhosis (n = 17)	F/H	P value
FBG	5.65 (5.20, 6.17)	6.07 (5.49, 6.64)	5.04 (4.86, 6.87)	4.413	0.110
CHO	5.50 (4.72, 6.36)	5.71 (5.06, 6.88)	5.14 (4.24, 6.11)	3.614	0.164
TG	1.44 (0.97, 1.69)^b	1.93 (1.46, 2.46)	1.25 (0.97, 1.46)^c	21.567	0.000
HDL	1.47 (1.26, 1.79)	1.37 (1.24, 1.53)	1.42 (1.15, 1.56)	3.219	0.200
LDL	3.59 (2.08, 4.42)	3.82 (3.03, 4.57)	3.23 (2.54, 3.92)	4.738	0.094
ALT	31.55 (21.80, 63.45)^d	83.50 (50.00, 156.60)	33.30 (16.95, 73.95)^e	20.514	0.000
AST	24.00 (18.33, 35.10)	46.00 (34.10, 76.00)^f	42.70 (24.35, 53.50)^g	26.408	0.000
ALP	79.50 (68.00, 100.23)	77.80 (66.30, 87.30)	82.60 (70.20, 107.35)	0.866	0.648
GGT	89.95 (39.53, 129.03)	69.00 (45.50, 100.90)	58.80 (30.95, 93.45)	1.718	0.424
TBIL	15.10 (12.23, 25.15)	13.90 (12.20, 16.60)	17.81 (12.10, 22.75)	5.088	0.079
DBIL	1.70 (1.40, 3.85)	1.90 (1.40, 2.40)	2.20 (1.20, 2.95)	0.446	0.800
IgG	12.16 (10.64, 13.52)	10.95 (10.04, 13.09)	11.77 (9.83, 15.33)	2.586	0.275
IgM	0.89 (0.72, 1.21)	0.85 (0.60, 1.09)	1.07 (0.85, 1.36)	3.501	0.174
IgA	2.46 ± 0.89^a	2.72 ± 0.88	3.21 ± 1.13	3.839	0.025

^aP = 0.02 vs cirrhosis group.

^bP < 0.001 vs cirrhosis group.

^cP = 0.001 vs NASH group.

^dP < 0.001 vs NASH group.

^eP = 0.004 vs NASH group.

^fP < 0.001 vs NAFL group.

^gP = 0.037 vs NAFL group.

FBG: Fasting blood glucose; CHO: Cholesterol; TG: Triglyceride; HDL: High density lipoprotein; LDL: Low density lipoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Glutamyl transferase TBIL: Total bilirubin; DBIL: Direct bilirubin.

Table 4 Comparison of autoantibody detection rates in three groups, n (%)

	NAFLD (n = 104)	NAFL (n = 36)	NASH (n = 51)	Cirrhosis (n = 17)	H	P value
Antibody¹	53 (51.0)	20 (55.6)	22 (43.1)	11 (64.7)	0.702	0.242
ANA	50 (48.1)	18 (50)	21 (41.2)	11 (64.7)	2.909	0.233
Cytoplasmic speckled	10 (9.6)	3 (8.3)	4 (7.8)	3 (17.6)	1.514	0.521
Nuclear speckled	25 (24.0)	11 (30.6)	10 (19.6)	4 (23.5)	1.388	0.500
Nuclear homogeneous	9 (8.6)	3 (8.3)	5 (9.8)	1 (5.9)	0.255	0.880
Nuclear discrete nuclear nots	2 (1.9)	1 (2.8)	0	1 (5.9)	2.552	0.279
Nuclear nucleolar	8 (7.7)	2 (5.6)	3 (5.0)	3 (17.6)	2.839	0.242
Cytoplasmic fibrillar	1 (1.0)	0	1 (2.0)	0	1.049	0.592
AMA (M2)	3 (2.9)	1 (2.8)	2 (3.9)	0	1.435	1
ASMA	7 (6.7)	4 (11.1)	2 (3.9)	1 (5.9)	1.780	0.450
Anti-sp100	4 (3.9)	3 (8.3)	1 (2.0)	0	2.286	0.374
Anti-gp210	2 (1.9)	1 (2.8)	1 (2.0)	0	0.703	1
Anti-SSA-RO52	4 (3.9)	2 (5.6)	1 (2.0)	1 (5.9)	1.476	0.493
Anti-SSA-RO60	6 (5.8)	2 (5.6)	2 (3.9)	2 (11.8)	1.707	0.448
SSB-La	3 (2.9)	2 (5.6)	0	1 (5.9)	3.437	0.167
Others²	10 (9.6)	3 (8.3)	4 (7.8)	3 (17.6)	1.643	0.494

¹Autoantibody was positive for any autoantibody.

²Anti-Jo-1, ACA, Anti-ribosomal p protein antibody, (anti nucleosome antibody, ANuA), Anti-U1-snRNP antibody, Anti-SM-D antibody.

NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; ANA: Antinuclear antibody; AMA: Anti-mitochondrial antibody; ASMA: Anti-smooth muscle antibody.

Table 5 Comparison of pathologic microscopic features in three groups, n (%)

	NAFLD (n = 104)	NAFL (n = 36)	NASH (n = 51)	Cirrhosis (n = 17)	P value
Portal enlargement	87 (83.7)	27 (75.0)	46 (90.2)	14 (82.4)	0.188
Portal lymphoplasmacytic infiltration	10 (9.6)	1 (2.8)^a	3 (5.9)^a	6 (35.3)	0.0022
Small bile duct changes
Hyperplasia	17 (16.3)	3 (8.3)^b	5 (9.8)¹^,^b	9 (52.9)²	< 0.001
Paucity	3 (2.9)	0	1 (2.0)	2 (11.8)	0.069
Interface hepatitis	19 (18.3)	1 (2.8)^b	8 (15.7)^a	10 (58.8)	< 0.001
Hepatocellular rosettes	2 (1.9)	0	0	2 (11.8)	0.025

¹1 patient with both bile duct paucity and hyperplasia.

²2 patients had both bile duct paucity and hyperplasia.

^aP < 0.05 vs cirrhosis group.

^bP < 0.001 vs cirrhosis group.

NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.

Citation: Zhu YJ, Zhang Y, Rao Y, Jiang Y, Liu YG, Li JZ, Yuan JQ, Zhao Y, Zheng WW, Ma L, Wang CY, Li J. Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology. World J Hepatol 2024; 16(12): 1407-1416
URL: https://www.wjgnet.com/1948-5182/full/v16/i12/1407.htm
DOI: https://dx.doi.org/10.4254/wjh.v16.i12.1407