Background
Methods
Study population and study design
Sub-grouping of AIH patients according to HLA-DR4
Histological examination
Criteria of acute or chronic AIH
Distribution of HLA-DR antigens in AIH
Treatment of AIH patients
Statistical analysis
Results
Frequency of HLA-DR phenotypes in AIH patients
HLA–DR phenotype | Autoimmune hepatitis (n = 132) | Control subjects (n = 31973) | P–value | Odds ratio (95 % Cl) |
---|---|---|---|---|
1 | 16 (11.9 %) | 3645 (11.4 %) | 0.795 | 1.07 (0.63–1.81) |
4
|
80 (59.7 %)
|
13365 (41.8 %)
|
<0.001
|
2.14 (1.51–3.04)
|
7 | 1 (0.7 %) | 239 (0.75 %) | 0.622 | 1.01 (0.14–7.28) |
8 | 38 (28.4 %) | 7513 (23.5 %) | 0.153 | 1.32 (0.90–1.92) |
9 | 27 (20.1 %) | 8505 (26.6 %) | 0.111 | 0.71 (0.46–1.08) |
11 | 2 (1.5 %) | 1644 (5.143 %) | 0.092 | 0.28 (0.07–1.15) |
12 | 8 (6.0 %) | 3485 (10.9 %) | 0.100 | 0.53 (0.26–1.08) |
13 | 14 (10.4 %) | 4029 (12.6 %) | 0.577 | 0.82 (0.44–1.43) |
14 | 25 (18.7 %) | 4348 (13.6 %) | 0.074 | 1.48 (0.96–2.30) |
15 | 34 (25.4 %) | 10647 (33.3 %) | 0.066 | 0.69 (0.47–1.03) |
16 | 3 (2.2 %) | 575 (1.8 %) | 0.935 | 1.27 (0.40–4.00) |
17 | 1 (0.7 %) | 88 (0.28 %) | 0.824 | 2.77 (0.38–20.0) |
6 *1 | 3 (2.2 %) | – |
Comparison of clinical features between HLA-DR4–positive and HLA-DR4–negative AIH
HLA–DR4–positive AIH (n = 78) | HLA-DR4-negative AIH (n = 54) | P–value | |
Discrete traits | N (%) | N (%) | |
Sex | 0.524 | ||
Male | 8 (10.3) | 3 (5.6) | |
Female | 70 (89.7) | 51 (94.4) | |
Pattern of disease onset Acute onset | 27 (34.6) | 20 (37.0) | 0.854 |
Other autoimmune diseases | 16 (20.5) | 7 (13.0) | 0.352 |
Death from liver disease–related causes | 3 (3.8) | 5 (9.3) | 0.271 |
ANA positivity | 71 (91.0) | 44 (81.5) | 0.121 |
ANA (<40/40/80/>80) | 7/9/18/44 | 10/8/10/26 | 0.435 |
AMA positivity | 9 (11.5) | 4 (7.4) | 0.558 |
Splenomegaly | 21 (27.6) | 23 (44.2) | 0.090 |
Fibrosis stage (F0–F2/F3–F4) | 38/31 | 31/16 | 0.255 |
Continuous traits | Median (Min–Max) | Median (Min–Max) | P–value |
Age (years) |
56 (15–86)
|
65 (9–88)
|
0.034
|
Total bilirubin (mg/dl) | 1.1 (0.4–20.4) | 1.1 (0.5–33.2) | 0.957 |
Aspartate aminotransferase (U/L) | 203.5 (21–2738) | 254.5 (20–1536) | 0.930 |
Alanine aminotransferase (U/L) | 270 (15–2325) | 284 (16–2016) | 0.779 |
Alkaline phosphatase (U/L) | 448.5 (213–1145) | 459 (131–1463) | 0.860 |
Gamma–glutamyl transpeptidase (IU/L) | 145.5(26–1404) | 147.5 (20–679) | 0.842 |
Prothrombin time (%) | 86 (29–130) | 82 (3–130) | 0.251 |
Albumin (g/dL) | 3.7 (1.9–4.7) | 3.8 (2.2–4.7) | 0.239 |
Platelets (x 104/nL) | 17.7 (8.9–39.6) | 17.55 (6.8–31.5) | 0.185 |
Immunoglobulin G (mg/dL) |
2582.5 (938–6750)
|
2074.5 (945–4961)
|
<0.001
|
Immunoglobulin M (mg/dL) |
181 (62–1720)
|
115 (47–888)
|
0.007
|
AIH score (except for histology score) | 14 (6–18) | 13 (7–17) | 0.117 |
AIH score (including histology score) | 18 (9–22) | 17 (8–22) | 0.450 |
Differences in the effect of HLA-DR4 between young-to-middle-aged and elderly AIH patients
HLA-DR4-positive AlH (n = 22) | HLA-DR4-negative AIH (n = 27) | P-value | |
Discrete traits | N (%) | N (%) | |
Sex | 0.084 | ||
Male | 3 (13.6) | 0 (0) | |
Female | 19 (86.4) | 27 (100) | |
Pattern of disease onset Acute onset | 4 (18.2) | 11 (40.7) | 0.123 |
Other autoimmune diseases | 4 (18.2) | 2 (7.4) | 0.388 |
Death from liver disease-related causes | 2 (9.10 | 3 (11.1) | 1.000 |
ANA positivity | 22 (100) | 24 (88.9) | 0.242 |
ANA (<40/40/80/<80) | 0/1/6/15 | 3/5/6/13 | 0.065 |
AMA positivity | 5 (22.7) | 2 (7.4) | 0.219 |
Splenomegaly | 9 (40.9) | 8 (30.8) | 0.548 |
Fibrosis stage (F0-F2/F3-F4) | 6/11 | 16/7 | 0.053 |
Continuous traits | Median (Min-Max) | Median (Min-Max) | P-value |
Age (years) | 72 (65–86) | 73 (66–88) | 0.657 |
Total bilirubin (mg/dL) | 1.1 (0.5–19.0) | 1.1 (0.5–33.2) | 0.976 |
Aspartate aminotransferase (U/L) | 188 (58–1177) | 290 (20–641) | 0.376 |
Alanine aminotransferase (U/L) | 191 (62–1208) | 284 (16–714) | 0.330 |
Alkaline phosphatase (U/L) | 441.5 (239–1145) | 443 (170–793) | 0.802 |
Gamma-glutamyl transpeptidase (IU/L) | 130.5 (47–466) | 203 (20–587) | 0.287 |
Prothrombin time (%) | 80.5 (30–104.8) | 82 (49–114.4) | 0.481 |
Albumin (g/dL) | 3.5 (2.2–4.5) | 3.8 (2.2–4.6) | 0.190 |
Platelets (x 104/pL) | 14.85 (9.6–27.7) | 15.7 (8.0–28.8) | 0.920 |
Immunoglobulin G (mg/dL) |
2724.5 (1758–5495)
|
2030 (1243–3157)
|
<0.0001
|
Immunoglobulin M (mg/dL) |
215 (62–1330)
|
98 (47–396)
|
0.003
|
AIH score (except for histology score) | 14 (7–17) | 13 (7–16) | 0.053 |
AIH score (including histology score) |
19 (12–22)
|
17 (8–21)
|
0.037
|
HLA-DR4-positive AIH (n = 34) | HLA-DR4-negative AIH (n = 15) | P-value | |
Discrete traits | N (%) | N (%) | |
Sex | 1.000 | ||
Male | 5 (14.7) | 2 (13.3) | |
Female | 29 (85.3) | 13 (86.7) | |
Pattern of disease onset Acute onset | 17 (50.0) | 7 (46.7) | 1.000 |
Other autoimmune diseases | 7 (20.6) | 4 (26.7) | 0.717 |
Death from liver disease-related causes | 1 (2.9) | 0 (0) | 1.000 |
ANA positivity | 28 (82.4) | 10 (66.7) | 0.275 |
ANA (<40/40/80/>80) | 7/5/9/13 | 5/2/2/6 | 0.642 |
AMA positivity | 4 (11.8) | 1 (6.7) | 1.000 |
Splenomegaly |
6 (18.8)
|
10 (71.4)
|
0.002
|
Fibrosis stage (F0-F2/F3-F4) | 23/8 | 8/5 | 0.478 |
Continuous traits | Median (Min-Max) | Median (Min-Max) | P-value |
Age (years) | 46.5 (15–54) | 36 (9–54) | 0.178 |
Total bilirubin (mg/dL) | 1.1 (0.4–30.4) | 1.1 (0.6–18.6) | 0.965 |
Aspartate aminotransferase (U/L) | 313.5 (21–2314) | 213 (42–1536) | 0.957 |
Alanine aminotransferase (U/L) | 499.5 (15–2207) | 252 (39–2016) | 0.983 |
Alkaline phosphatase (U/L) | 477 (245–732) | 491 (184–1463) | 0.357 |
Gamma-glutamyl transpeptidase (IU/L) | 181 (26–1404) | 166 (23–679) | 0.558 |
Prothrombin time (%) | 94 (29–130) | 85 (47–130) | 0.389 |
Albumin (g/dL) | 4.0 (2.2–4.7) | 4.1 (2.9–4.7) | 0.267 |
Platelets (x 104/pL) | 21.65 (9.7–39.6) | 18.0 (8.5–31.5) | 0.175 |
Immunoglobulin G (mg/dL) | 2116.5 (938–6750) | 2305 (945–4961) | 0.374 |
Immunoglobulin M (mg/dL) | 179.5 (65–890) | 231 (59–888) | 0.428 |
AIH score (except for histology score) | 12 (6–16) | 13 (8–17) | 0.197 |
AIH score (including histology score) | 16 (9–21) | 17 (9–22) | 0.112 |
Treatment outcome and HLA-DR antigens
Non-refractory group (n = 106) | Refractory group (n = 15) | P-value | |
Discrete traits | N (%) | N (%) | |
Sex | 0.356 | ||
Male | 11 (10.4) | 0 (0) | |
Female | 95 (89.6) | 15 (100) | |
Pattern of disease onset |
45 (42.5)
|
2 (13.3)
|
0.045
|
Acute onset | |||
Other autoimmune diseases | 19 (17.9) | 3 (20.0) | 0.735 |
Death from liver disease-related causes |
0 (0)
|
8 (53.3)
|
<0.001
|
ANA positivity | 92 (86.8) | 13 (86.7) | 1.000 |
ANA (<40/40/80/>80) | 14/15/18/59 | 2/2/6/5 | 0.274 |
AMA positivity | 13 (12.3) | 0 (0) | 0.366 |
Splenomegaly |
32 (30.8)
|
9 (60.0)
|
0.038
|
Fibrosis stage (F0-F2/F3-F4) | 55/42 | 5/4 | 1.000 |
Continuous traits | Median (Min-Max) | Median (Min-Max) | P-value |
Age (years) | 57 (9–87) | 64 (46–85) | 0.167 |
Total bilirubin (mg/dL) |
1.1 (0.4–30.4)
|
5.1 (0.8–33.2)
|
0.001
|
Aspartate aminotransferase (U/L) | 248 (21–2738) | 133 (46–1130) | 0.229 |
Alanine aminotransferase (U/L) | 310 (15–2325) | 284 (30–741) | 0.429 |
Alkaline phosphatase (U/L) |
456 (131–1463)
|
564 (420–830)
|
0.007
|
Gamma-glutamyl transpeptidase (IU/L) | 161 (26–679) | 192 (48–1404) | 0.532 |
Prothrombin time (%) |
86 (29–130)
|
73 (43–109.1)
|
0.002
|
Albumin (g/dL) |
3.8 (1.9–4.7)
|
3.2 (2.7–4.0)
|
0.004
|
Platelets (x 10
4
/μL) |
18.0 (8.9–39.6)
|
11.1 (6.8–36.8)
|
0.016
|
Immunoglobulin G (mg/dL) | 2536 (938–6750) | 2163(1654–5495) | 0.514 |
Immunoglobulin M (mg/dL) | 135.5 (47–1720) | 172.5 (52–321) | 0.618 |
AIH score (except for histology score) | 14 (6–18) | 13 (9–16) | 0.748 |
AIH score (including histology score) | 18 (8–22) | 17 (9–21) | 0.284 |