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RNSSON ET AL.
BJO
2041
2042
RNSSON ET AL.
BJO
Results
General Characteristics of the Patients. A total of
261 well-characterized AIH cases were identied with
the available clinical, laboratory, and histological data
required for diagnosis according to the new simplied
criteria. Overall, 560 cases were excluded because of
an earlier diagnosis of AIH outside the Mayo Clinic,
and many of these patients were on treatment when
rst seen at the Mayo Clinic. Decompensated liver disease at presentation was found in 125 patients, and 70
had undergone transplantation for AIH, 57 had not
undergone a liver biopsy, 39 did not have available
data on autoantibodies or gamma globulins, three had
only family history of AIH, and 256 did not have
AIH as their nal diagnosis. Other cases excluded were
for suspicion of overlap syndromes with primary biliary cirrhosis and primary sclerosing cholangitis (n
97) and pediatric cases (n 68).
RNSSON ET AL.
BJO
2043
Table 1. Comparison of the Demographics, Seropositivity, AIH Score, Histology, Treatment, and Liver Tests at Presentation in
Patients with Autoimmune Hepatitis (AIH) and Those with Drug-Induced Liver Injury (DIAIH)
AIH Patients (n 5 237)
Age
Sex, females (%)
ANA positive (%)
SMA positive (%)
Both ANA and SMA (%)
Seronegative (%)
Simplied AIH score:
Probable or denite (%)
Immunosuppressive therapy (%)
Steroids and azathioprine (%)
Steroids alone (%)
Trial of discontinuation successful (%)
AST (<48 U/L)
ALT (<55 U/L)
ALP (115 U/L)
TB (<1.0 mg/dL)
Albumin (>3.5 g/dL)
INR (<1.2)
IgG (<1500 g/dL)
Gamma globulins (<1.7 g/dL)
Jaundice at presentation
DIAIH (n 5 24)
52
184
165/237
106/237
69/237
29/237
(37-62)
(78%)
(70%)
(45%)
(29%)
(12%)
53
20
20
12/24
9/24
1/24
(24-61)
(92%)
(83%)
(50%)
(38%)
(4%)
181/237
222/237
191/222
31/222
18/52
392
480
241
2.0
3.4
1.1
2020
2.5
110/237
(76%)
(94%)
(86%)
(14%)
(35%)
(154-1031)
(185-1141)
(138-350)
(1.0-8.0)
(2.95-3.7)
(1.0-1.3)
(1618-2702)
(2.0-3.2)
(46%)
19/21
21/24
12/21
9
14/14
679
728
376
4.0
3.1
1.1
1905
2.55
12/24
(90.5%)
(88%)
(57%)
(43%)
(100%)
(291-956)
(255-1141)
(229-514)
(1.0-12.0)
(2.6-3.6)
(1.0-1.3)
(1600-2455)
(2.2-3.1)
(50%)
P Value
NS
NS
NS
NS
NS
NS
NS
NS
0.0024
0.0024
<0.0001
NS
NS
0.0166
NS
NS
NS
NS
NS
NS
Table 2. Comparison of the Demographics, Seropositivity, AIH Score, Histology, Treatment and Liver Tests at Presentation in
Patients with Nitrofurantoin-Induced and Minocycline-Induced AIH
Nitrofurantoin AIH (n 5 11)
Age
Sex, females (%)
Duration of therapy (months)
ANA positive (%)
SMA positive (%)
Both ANA and SMA (%)
Seronegative (%)
Simplied AIH score:
Probable or denite (%)
Compatible histology (%)
Typical histology (%)
Immunosuppressive therapy (%)
Steroids and azathioprine (%)
Steroids alone (%)
Trial of discontinuation successful (%)
AST (<48 U/L)
ALT (<55 U/L)
ALP (115 U/L)
TB (<1.0 mg/dL)
Albumin (>3.5 g/dL)
INR (<1.2)
IgG (<1500 g/dL)
Gamma globulins (<1.7 g/dL)
Jaundice at presentation
61
11
24
8/11
6/11
4/11
1/11
7/9
6/11
5/11
11/11
3/11
8/11
9/9
827
778
426
7
2.9
1.2
1835
2.5
8/11
P value
(54-66)
(100%)
(8-36)
(73%)
(55%)
(36%)
(9%)
24
10
12
10/11
5/11
4/11
0/11
(18-38)
(91%)
(9-36)
(91%)
(45%)
(36%)
(0%)
0.0019
NS
NS
NS
NS
NS
NS
(78%)
(55%)
(45%)
(100%)
(27%)
(73%)
(100%)
(516-1401)
(448-1159)
(314-503)
(2.7-21.0)
(2.6-3.4)
(1.0-1.4)
(1275-2455)
(1.9-2.6)
(73%)
10/10
2/11
9/11
9/11
8/9
1/11
5/5
329
380
188
1.5
3.4
1.1
1905
2.8
3/11
(100%)
(18%)
(82%)
(82%)
(89%)
(11%)
(100%)
(168-726)
(213-871)
(110-1081)
(0.8-7.5)
(2.8-3.5)
(0.9-1.3)
(1790-2580)
(2.3-3.8)
(27%)
NS
NS
NS
NS
0.0098
0.0098
NS
0.0235
NS
NS
NS
NS
NS
NS
NS
NS
In two nitrofurantoin cases and one minocycline case, gamma globulin levels were not available, which made it possible to calculate the AIH score in 19
patients.
2044
RNSSON ET AL.
BJO
DIAIH
AIH
P Value
3 (2-3)
2 (2-3)
3 (2-3)
2 (2-3)
NS
NS
19/23
2.5
2.0
15/23
7/23
7/22
0
8/24
16/24
(83%)
(1.5-3.0)
(1.0-3.0)
(65%)
(30.4%)
(31.8%)
(0-2)
(33%)
(66%)
0
22/23
2.0
2.0
12/22
2/22
5/22
1
8/24
15/24
1/24
(96%)
(1.0-3.0)
(1.0-3.0)
(55%)
(9%)
(22.7%)
(0-3)
(33%)
(63%)
(4%)
NS
NS
NS
NS
NS
NS
0.06
NS
Results are expressed as medians and interquartile range. Grade, portal inammation, interface, and lobular hepatitis as well as stage are scored as none, mild,
moderate, and severe. Lymphoplasmacytic occurrence, zone 3 necrosis, conuent
necrosis, and rosette formation are classied as present or absent.
3 (3-3.8)
3 (2-3)
10/10 (100%)
3.0 (3.0-3.0)
3.0 (2.0-4.0)
9/10 (90%)
6/10 (30.4%)
6/9 (66%)
0 (0-2)
6/11 (55%)
5/11 (45%)
0
Minocycline
P Value
2 (2-3)
2 (2-3)
0.0082
0.08
9/11 (82%)
2.0 (1.0-2.8)
1.0 (1.0-2.0)
6/11 (55.5%)
1/11 (9%)
1/11 (9%)
0 (0-1.8)
2/11 (18%)
9/11 (82%)
0
NS
0.0053
0.0072
NS
0.024
0.0166
NS
NS
RNSSON ET AL.
BJO
2045
Discussion
2046
RNSSON ET AL.
BJO
F55
F55
F53
F64
F55
F75
F52
F67
F67
F66
F64
(27)
(36)
(6)
(7)
(4)
(60)
(36)
(36)
(12)
(36)
(24)
ANA
SMA
IgG
Gamma-globulins
Score
AST
ALT
ALP
TB
Therapy
Response to Therapy
neg
neg
1:320
neg
5.6
5.3
>12
1.8
>12
1:80
6.3
1:40
1:20
1:160
1:80
neg
1:20
1:1280
1:20
neg
1:80
1:40
2850
1440
1750
2230
2.9
1.8
2.2
2.5
1.8
3.6
1.3
1.8
2.6
7
6
6
7
7
6
6
6
7
282
2069
827
436
918
1725
814
1538
993
300
757
336
1479
1059
188
1165
1141
778
1652
729
450
448
327
426
341
470
1195
499
229
276
514
2.7
37.1
1.8
1.1
7.8
20.6
4.5
30.9
10.6
0.9
3.5
Steroids
Steroids
Steroids
Steroids
Steroids
Steroids
Steroids
SterAza
SterAza
SterAza
SterAza
Fair*
Good
Good
Good
Good
Good
Good
Good
Good
Good
Good
F, female; M, male.
*Information not available on discontinuation of immunosuppression.
Discontinuation of immunosuppression successful.
Discontinuation of immunosuppression not tried.
Table 6. Clinical Characteristic of the Individual Patients with Minocycline Induced AIH
Subject, Duration of Therapy (months)
ANA
SMA
IgG
Gamma-globulins
Score
AST
ALT
ALP
TB
Therapy
Response to Therapy
F24 (36)
F39 (-)
F60 (8)
F25 (42)
F17 (-)
F55 (2)
F33 (4)
F25 (-)
F17 (12)
F18 (36)
M18 (12)
1:40
2.9
neg
1:320
1:80
1:80
>12
1.5
>12
>12
3.6
neg
neg
1:160
1:160
1:40
1:40
1:640
1:20
neg
neg
neg
1820
1670
1990
3170
1760
1620
2.4
2.0
2.8
2.88
4.6
1.2
3.5
1.7
2.2
6
7
7
7
7
6
7
6
7
7
449
785
178
329
328
769
1412
267
600
165
78
728
1035
283
213
478
871
2079
389
245
127
595
1243
188
1963
151
122
106
0.8
11.1
0.5
1.5
0.9
13.3
3.5
0.9
0.7
0.9
0.5
SterAza
SterAza
Steroids
SterAza
SterAza
None
SterAza
SterAza
SterAza
SterAza
None
Good*
Good
Good
Good
Good
Good
Good*
Good*
Good*
-
F, female; M, male.
*Discontinuation of immunosuppression not tried.
Discontinuation of immunosuppression successful.
RNSSON ET AL.
BJO
2047
opment of AIH in several patients associated with several different drugs. In these patients, immunosuppression could also be discontinued without a relapse,32
which is in line with the results of the current series.
Our results suggest that in patients with DIAIH a trial
of discontinuation of immunosuppression should be
undertaken in all patients.
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