Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes

Porta, Gilda; Carvalho, Elisa de; Santos, Jorge L.; Gama, Jorge; Borges, Cristian V.; Seixas, Renata B.P.M.; Ferreira, Alexandre R.; Miura, Irene K.; Silveira, Themis R.; Silva, Luciana R.; Fagundes, Eleonora D.T.; Bellomo-Brandao, Maria A.; Sawamura, Regina; Vieira, Sandra M.; Melere, Melina U.; Marques, Cibele D.F.; Pugliese, Renata P.; Danesi, Vera L.; Porta, Adriana; Marsillac, Marise E.; Valladares, Marcia A.; Menezes, Daniela G.; Kieling, Carlos; Paula, Mariana N. de; Vasconcelos, Juliana R.; Ferreira, Cristina T.; Perin, Nilza; Resende, Leonardo R.; Maia, Jussara; Tommaso, Adriana M.A. De; Hessel, Gabriel

doi:10.1016/j.jped.2018.04.007

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Original articles • J. Pediatr. (Rio J.) 95 (4) • Jul-Aug 2019 • https://doi.org/10.1016/j.jped.2018.04.007 copy

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes^☆ ☆ Please cite this article as: Porta G, Carvalho E, Santos JL, Gama J, Borges CV, Seixas RB, et al. Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes. J Pediatr (Rio J). 2019;95:419 -27.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis.

Methods:

The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments.

Results:

Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%).

Conclusions:

In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

KEYWORDS
Autoimmune hepatitis; Clinical; Laboratory; Treatments; Outcomes; Brazil

Parameters	AIH-1	AIH-2	OR AIH-1/AIH-2 (95% CI); logistic regression	p
Age at onset (months)
Median (min; max)	111.5 (6; 210)	53.5 (8; 165)		<0.001^a a Mann -Whitney test.
Age at diagnosis (months)
Median (min; max)	122.5 (6; 219)	68.0 (12; 200)		<0.001^a a Mann -Whitney test.
Gender
Male, n (%)	186 (25.1%)	13 (15.1%)	1.88 (1.02, 3.47)	0.044^b b Wald test.
Female, n (%)	556 (74.9%)	73 (84.9%)	1
Clinical presentation
Acute, n (%)	410 (56.1%)	50 (58.8%)	1.11 (0.71, 1.76)	0.630^b b Wald test.
Insidious, n (%)	321 (43.9%)	35 (41.2%)	1
Fulminant				0.005^b b Wald test.
Yes, n (%)	27 (3.6%)	9 (10.6%)	0.32 (0.14, 0.70)
No, n (%)	715 (96.4)	76 (89.4)	1
Hepatic failure
INR > 1.5, n (%)	226 (30.7)	31 (40.3)		0.060^b b Wald test.
Extrahepatic manifestations
Yes, n (%)	183 (24.8)	12 (14.1)	2.01 (1.07, 3.77)	0.031^b b Wald test.
No, n (%)	555 (75.2)	73 (85.9)	1
Family history of autoimmune disease
Yes, n (%)	161 (21.9%)	18 (21.2%)	1.42 (0.60, 1.80)	0.883^b b Wald test.
No, n (%)	575 (78.1%)	67 (78.7)	1
AIH score (1999)
Median (min; max)	17 (7; 28)	15.5 (3; 123)		0.001^a a Mann -Whitney test.
Score (2008)
Median (min; max)	7 (2; 10)	6 (3; 9)		0.001^a a Mann -Whitney test.

Parameters	AIH-1	AIH-2	OR AIH-1/AIH-2 (95% CI); Logistic regression	p
AST (× UNL)
Median (min; max)	18 (0; 169)	13 (0.7; 153)		0.315^a a Mann -Whitney test.
ALT (× UNL)
Median (min; max)	13 (0; 156)	12.5 (0.8; 88)		0.521^a a Mann -Whitney test.
GGTP (× UNL)
Median (min; max)	3 (0; 37)	3 (0; 17)		0.368^a a Mann -Whitney test.
ALP (× UNL)
Median (min; max)	1.3 (0; 47.7)	1.5 (0; 6.5)		0.365^a a Mann -Whitney test.
TB (mg/dL)
Median (min; max)	3.2 (0; 32.1)	3.9 (0.3; 66.2)		0.334^b b Wald test.
DB (mg/dL)
Median (min; max)	2.1 (0; 24)	1.8 (0.1; 37.4)		0.794^a a Mann -Whitney test.
Albumin (g/dL)
Median (min; max)	3.4 (0; 33)	3.6 (1.3; 5)		0.030^a a Mann -Whitney test.
Gammaglobulin (g/dL)
Median (min; max)	3.4 (0; 75)	2.2 (0.8; 6.2)		<0.001^a a Mann -Whitney test.
IgA - low, n (%)	12 (3.3)	13 (29.5)	0.10 (0.04; 0.24)	<0.001^b b Wald test.
IgM - high, n (%)	131 (37.4)	18 (40.9)	0.88 (0.46; 1.66)	0.685^b b Wald test.
IgG - high, n (%)	331 (83.6)	34 (63)	2.89 (1.55; 5.38)	0.001^b b Wald test.
C3 - low, n (%)	83 (29.0)	20 (46.5)	0.49 (0.251; 0.94)	0.032^b b Wald test.
C4 - low, n (%)	151 (53.9)	20 (46.5)	1.39 (0.73; 2.65)	0.317^b b Wald test.
Cholangiography (sclerosing cholangitis), n (%)	58 (19.9)	2 (11.8)	1.59 (0.34; 7.40)	0.551^b b Wald test.
Portal inflammation (moderate-severe)
Yes, n (%)	559 (93.9)	61 (88.4)	2.04 (0.91; 4.58)	0.085^b b Wald test.
No, n (%)	36 (6.1)	8 (11.6)	1
Interface hepatitis
Yes, n (%)	485 (83.3)	52 (77.6)	1.44 (0.78; 2.67)	0.243^b b Wald test.
No, n (%)	112 (17.3)	15 (22.4)	1
Rosettes
Yes, n (%)	310 (52.9)	24 (35.3)	2.06 (1.22; 3.47)	0.007^b b Wald test.
No, n (%)	276 (47.1)	44 (64.7)	1
Plasma cells
Yes, n (%)	315 (53.5)	21 (30.4)	2.63 (1.54; 4.50)	<0.001^b b Wald test.
No, n (%)	274 (46.5)	48 (69.6)	1
Fibrosis/cirrhosis
Fibrosis, n (%)	461 (77.9)	52 (77.6)	0.87 (0.49; 1.55)	0.636^b b Wald test.
Cirrhosis, n (%)	131 (22.1)	17 (24.6)	1
Bile duct injury
Yes, n (%)	56 (9.4)	5 (7.5)	1.29 (0.50; 3.34)	0.602^b b Wald test.
No, n (%)	539 (90.6)	62 (92.5)	1

Parameters	AIH-1 N (%)	AIH-2 N (%)	OR AIH-1/AIH-2 (95% CI); logistic regression	p
Remission
Yes, n (%)	543 (74.7)	76 (89.4)	0.35 (0.17; 0.71)	0.003^b b Wald test.
No, n (%)	184 (25.3)	9 (10.6)	1
Time to remission (months)
Median (min; max)	7 (0; 250)	4 (1; 149)		0.002^a a Mann -Whitney test.
Relapse numbers
Median (min; max)	3 (0; 13)	3 (0; 6)		0.433^a a Mann -Whitney test.
Treatment discontinuation
Yes, n (%)	49 (7.0)	8 (10.0)	0.68 (0.31; 1.48)	0.328^b b Wald test.
No, n (%)	653 (93.0)	72 (90.0)	1
LTx
Yes, n (%)	35 (4.7)	3 (3.5)	1.36 (0.41; 4.53)	0.613^b b Wald test.
No, n (%)	702 (95.3)	82 (96.5)	1
Death
Yes, n (%)	55 (7.5)	2 (2.4)	3.36 (0.80; 14.02)	0.047^b b Wald test.
No, n (%)	680 (92.5)	83 (97.6)	1

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[1] * Corresponding author. E-mail:gildaporta@gmail.com (G. Porta).