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45

9. 図

図の説明

図１. 本研究の概略図

図の赤い丸が潰瘍性大腸炎、黄色い丸が原発性硬化性胆管炎である。両者が重なっ

た部分が両疾患合併群である。検討 1 は潰瘍性大腸炎単独群と両者を合併した群の

比較、検討 2 は原発性硬化性胆管炎と両者合併群の比較である。

図２. 検討 1 の対象入院の抽出図

図のような条件、流れで解析対象集団を抽出し、2 群に分類した。

図３. 検討 2 の対象入院の抽出図

図のような条件、流れで解析対象手段を抽出し、2 群に分類した。

46

47

48

49

10. 表

表１ DPC データを用いた UC 単独群と UC-PSC 群の患者背景の比較

傾向スコアマッチング前

傾向スコアマッチング後

79099

UC

78838

別 (男

/ 女

492

UC-PSC

p値

261

UC

UC-PSC

246

246

p値

標準

44564 / 34252

188 / 73

<0.0001

177 / 69

177 / 69

44.4±20.5

32.7±17.5

<0.0001

37.1±19.2

31.8±16.6

0.0013

0.3

0-64 歳

62749

239

224

224

65 歳以上

16067

22

22

22

21.0±5.88

20.0±3.27

20.3±3.60

19.9±3.28

0.27

0.12

肥満 (≧25 kg/m²)

10457

22

86

86

標準体型 (18.5-24.9 kg/m²)

46033

147

139

139

やせ型 (<18.5 kg/m²)

20083

90

21

21

15211 (19.3)

20 (7.7)

<0.0001

20(8.1)

20(8.1)

(%)

20815 (26.4)

128 (49.0)

<0.0001

119(48)

119(48)

期間中央値 (四分位)

16 日 (6-29)

17 日 (8-30)

0.4

平均年齢 (平均±標準偏差)

年齢層

BMI (平均±標準偏差), kg/m²

0.0068

BMI 層別

喫煙者(%)

Charlson Comobidity index

点数

<0.0001

0点

59512

133

1 点

13818

76

2点

4047

24

3 点以上

1476

13

心筋梗塞(%)

415 (0.53)

0 (0)

0.24

うっ血

心不全 (%)

660 (0.84)

3 (1.2)

0.58

末梢血

疾患(%)

308 (0.39)

1 (0.38)

0.98

脳血 障害(%)

1115 (1.4)

0 (0)

0.05

認知 (%)

367 (0.47)

0 (0)

0.27

慢 肺疾患(%)

1847 (2.3)

2 (0.77)

0.09

747 (0.95)

3 (1.2)

0.74

(%)

7841 (9.9)

33 (12.6)

0.15

軽度肝障害(%)

1875 (2.4)

54 (20.7)

<0.0001

Charlson Comobidity index

(%)

50

糖尿 (%)

4503 (5.7)

26 (10.0)

0.003

のあ 糖尿 (%)

459 (0.58)

1 (0.38)

0.67

片麻痺(%)

48 (0.06)

0 (0)

0.69

慢 腎不全(%)

483 (0.61)

2 (0.77)

0.75

悪 腫

(%)

2343 (3.0)

14 (5.3)

0.02

転移 癌(%)

121 (0.15)

0 (0)

0.53

重 肝障害(%)

37 (0.05)

6 (2.3)

<0.0001

AIDS(%)

39 (0.05)

0 (0)

0.72

DPC, diagnosis procedure combination; UC, ulcerative colitis; PSC, primary sclerosing cholangitis;

BMI, body mass index; AIDS, acquired immunodeficiency syndrome

51

表２. DPC を用いた UC 単独群と UC-PSC 群の治療内容や合併症の比較

傾向スコアマッチング前

傾向スコアマッチング後

79099

UC

78838

ステロイド強力静注

法(%)

UC-PSC

492

p値

UC

261

UC-PSC

246

246

p値

21928 (28)

55 (21)

0.012

76 (31)

52 (21)

0.001

16781 (21)

39 (15)

0.01

56 (22.8)

37 (15.0)

0.02

インフリキシマブ(%)

13003 (16)

25 (9.6)

0.003

46 (18.7)

24 (9.8)

0.004

アダリムマブ(%)

3023 (3.8)

12 (4.6)

0.41

9 (3.7)

11 (4.5)

0.64

ゴリムマブ(%)

726 (0.92)

3 (1.2)

0.7

1 (0.4)

3 (1.2)

0.3

ベドリズマブ(%)

185 (0.23)

0 (0)

0.43

1 (0.41)

0 (0)

0.24

トファチニブ(%)

208 (0.26)

0 (0)

0.41

1 (0.41)

0 (0)

0.24

12649 (16)

46 (18)

0.49

45 (18.3)

44 (17.9)

0.9

2504 (3.2)

10 (3.8)

0.34

13 (5.3)

9 (3.7)

0.38

癌(%)

1437 (1.82)

9 (3.45)

0.08

7 (2.85)

9 (3.66)

0.61

癌(%)

12 (0.02)

6 (2.3)

<0.0001

0 (0)

5 (2.0)

0.008

418 (0.53)

2 (0.77)

0.6

1 (0.41)

2 (0.81)

0.56

生物学的製剤(%)

白血球系細胞除去

外科手術(%)

内死亡数(%)

法(%)

DPC, diagnosis procedure combination; UC, ulcerative colitis; PSC, primary sclerosing cholangitis

52

表３. DPC データを用いた UC 症例の治療に関する多変量解析

臨床因子

79099

年齢層

BMI

ステロイド強力静注

: 44752

オッズ比

95％信頼区間

インフリキシマブ

p値

reference

オッズ比

95％信頼区間

0.83

0-64 歳: 62988

reference

0.80-0.86

0.66

0.63-0.69

肥満: 10479

0.81

0.77-0.86

通常体型: 46180

reference

やせ型: 20173

1.18

1.13-1.22

Yes: 15231

0.97

0.93-1.01

0.88

0.84-0.92

<0.0001

喫煙者

Yes: 15231

1.06

0.58

0.54-0.61

1.22

1.15-1.29

ステロイ

0.86

0.82-0.90

1.23

1.17-1.28

<0.0001

reference

1.02-1.11

1.02

reference

1.29-1.61

0.91

0.79-1.06

0.23

1.30

1.18-1.44

<0.0001

3.52

3.21-3.86

<0.0001

<0.0001

reference

0.97‐1.07

1.43

reference

Yes: 21983

0.98

No: 57116

reference

<0.0001

reference

0.94-1.03

2.38

2.17-2.60

0.56

<0.0001

reference

インフリ

Yes: 21983

0.69

キシマブ

No: 57116

reference

PSC 合

1.29-1.60

0.52

ド強力静

<0.0001

<0.0001

1.44

reference

0.003

No: 54816

0.70-0.85

reference

reference

<0.0001

p値

<0.0001

0.77

<0.0001

0.1

reference

95％信頼区間

reference

reference

65 歳以上: 16111

オッズ比

<0.0001

<0.0001

No: 58156

p値

reference

<0.0001

女 : 34325

手術

0.61-0.79

<0.0001

Yes: 261

0.66

0.49-0.90

0.48

0.008

No: 78838

reference

0.32‒0.74

0.93

0.0008

reference

UC, ulcerative colitis; PSC, primary sclerosing cholangitis; BMI, body mass index

53

0.45-1.90

0.84

reference

表 4. DPC を用いた PSC 単独群と PSC-UC 群の患者背景の比較

傾向スコアマッチング前

傾向スコアマッチング後

6226

PSC

5302

別 (男

/ 女

平均年齢 (平均±標準偏差)

1344

PSC-UC

p値

924

2939 / 2447

572 / 265

<0.0001

59.9 ±19.9

38.4±16.8

<0.0001

年齢層

PSC

PSC-UC

p値

672

672

470/202

445/227

0.14

39±0.69

<0.0001

44±0.69

<0.0001

標準

0.08

0.74

0-64 歳

2630

752

594

590

0.02

65 歳以上

2759

85

82

82

21.4±3.5

20.9±3.6

BMI (平均±標準偏差), kg/m²

0.0008

BMI 層別

21.0±0.14

20.7±0.14

0.0002

0.19

0.78

肥満 (≧25 kg/m²)

725

101

72

68

0.02

標準体型 (18.5-24.9 kg/m²)

3558

512

421

416

0.02

やせ型 (<18.5 kg/m²)

1010

214

169

181

0.04

心筋梗塞(%)

16(0.3)

2(0.2)

0.77

0(0)

2(0.3)

0.1

うっ血

心不全 (%)

126(2.3)

5(0.60)

0.0002

4(0.6)

5(0.67)

0.74

末梢血

疾患(%)

27(0.50)

1(0.12)

0.07

0(0)

0(0.1)

0.24

脳血 障害(%)

81(1.50)

2(0.43)

0.0004

0(0)

2(0.3)

0.1

認知 (%)

75(1.39)

3(0.36)

0.004

2(0.3)

3(0.45)

0.65

慢 肺疾患(%)

149(2.76)

14(1.67)

0.05

9(1.3)

13(1.9)

0.39

64(1.19)

5(0.60)

0.1

8(1.2)

5(0.74)

0.4

(%)

363(6.74)

52(6.21)

0.57

51(7.6)

46(6.6)

0.46

軽度肝障害(%)

1191(22.1)

238(28.4)

<.0001

176(26)

196(29)

0.22

Charlson Comobidity index

(%)

糖尿 (%)

593(11)

44(5.3)

<.0001

43(6.4)

34(5.1)

0.29

のあ 糖尿 (%)

73(1.35)

2(0.24)

0.001

4(0.6)

2(0.3)

0.41

片麻痺(%)

2(0.04)

0(0)

0.44

1(0.15)

0(0)

0.24

慢 腎不全(%)

67(1.24)

5(0.60)

0.08

11(1.6)

4(0.3)

0.06

悪 腫 (%)

439(8.15)

38(4.54)

0.0001

25(3.7)

32(4.8)

0.34

転移 癌(%)

21(0.4)

0(0)

0.014

2(0.3)

0(0)

0.25

293(5.44)

49(5.85)

0.63

46(6.9)

44(6.6)

0.83

0(0)

0(0)

重 肝障害(%)

AIDS(%)

Charlson Comobidity index

0.27

0.60

0点

3147

40

376

365

1 点

1740

19

195

196

54

2点

608

37

49

3 点以上

656

12

64

62

1039 (19)

109(13)

<0.0001

104(15)

100(15)

0.76

(%)

2228(41)

489(59)

<0.0001

431(64)

416(62)

0.40

0.05

期間中央値 (四分位)

9(5-17)

8(5-14)

0.0017

8(5-17)

8(5-15)

0.02

喫煙者(%)

DPC, diagnosis procedure combination; UC, ulcerative colitis; PSC, primary sclerosing cholangitis;

BMI, body mass index; AIDS, acquired immunodeficiency syndrome

55

表５. DPC を用いた PSC 単独群と PSC-UC 群の治療内容や合併症の比較

傾向スコアマッチング前

傾向スコアマッチング後

6226

PSC

5302

ドレナージ術(％)

PSC-UC

1344

p値

924

PSC

672

PSC-UC

p値

672

2225(41.3)

331(2556)

0.34

227(33.8)

256(38.1)

0.10

120(2.2)

16(1.9)

0.55

36(5.4)

15(2.2)

0.002

癌(%)

237(4.4)

19(2.3)

0.0019

17(2.5)

14(2.1)

0.59

癌(%)

40(0.7)

9(1.1)

0.33

4(0.6)

8(1.2)

0.24

7(0.13)

1(0.12)

0.94

1(0.15)

1(0.15)

2(0.04)

0(0)

0.45

0(0)

0(0)

5(0.09)

0(0)

0.23

0(0)

0(0)

210(3.9)

14(1.7)

0.0004

19(2.8)

13(1.9)

肝移植術(%)

肝切除術(%)

膵頭十二指

肝門部悪

切除術 (%)

内死亡(%)

切除術(%)

UC, ulcerative colitis; PSC, primary sclerosing cholangitis

56

0.28

表６. DPC を用いた PSC 症例の臨床イベントに関する多変量解析

ドレナージ

臨床因子

6226

年齢層

BMI

: 3511

オッズ

95％信頼区

p値

reference

オッズ比

95％信頼

区間

: 2712

0-64 歳: 3382

0.80

0.71-0.88

0.72-1.25

1.33-1.66

肥満: 826

1.05

0.90-1.22

標準体型: 4070

reference

やせ型: 1224

0.91

0.80-1.03

Yes: 2717

1.09

0.98-1.22

0.55

UC 合

reference

Yes: 1148

0.96

2.45

1.82-3.28

0.53

0.33-0.85

0.67-1.29

1.08

0.82-1.72

reference

Yes: 837

1.05

reference

0.64

0.89-1.69

0.58

0.28-1.16

0.12

2.03

1.40-2.97

0.0003

15.2

7.10-32.8

<0.0001

1.37

0.84-2.25

0.22

reference

0.90-1.23

0.01-0.13

reference

0.75

0.21

reference

0.46-1.23

0.56

No: 5389

0.0088

<0.0001

0.04

0.59

0.58

No: 5078

0.89

0.71-1.48

reference

0.93

1.22

p値

reference

reference

0.98-1.21

区間

<0.0001

reference

0.15

1.03

reference

1.48

95％信頼

reference

<0.0001

65 歳以上: 2844

オッズ

0.72

0.95

reference

No: 3509

p値

reference

<0.0001

0.11

喫煙者

肝移植術

0.40

0.26

reference

0.0007

reference

UC, ulcerative colitis; PSC, primary sclerosing cholangitis; BMI, body mass index;

57

0.23-0.68

表 7. 当院の UC 症例と UC-PSC 症例の患者背景の比較

UC

別(男 / 女

高齢者(％)

診断

高齢

年齢(平均±標準偏差)

(％)

生物学的製剤販売市販後診断(％)

UC-PSC

p値

966

27

541/425

20/7

0.045

195(20)

2(7.4)

0.07

32.4±14.8

25.7±9.34

0.0051

23(2.38)

0(0)

0.26

237(24)

9(33)

0.31

罹患範囲

<0.0001

139(14)

0(0)

左側

225(23)

0(0)

350(36)

13(48)

右側

5(0.52)

7(26)

その他

23(2.4)

0(0)

166(17)

１(3.7)

0.03

340(35)

4(15)

0.02

手術歴(％)

174(18)

3(11)

0.33

5ASA(％)

702(73)

22(81)

0.29

128(13)

2(7.4)

0.34

ステロイド(％)

332(34)

8(30)

0.6

抗 TNFα 抗体製剤(％)

198(21)

4(14)

0.21

インフリキシマブ(％)

154(16)

4(14)

0.87

アダリムマブ(％)

66(6.8)

0(0)

0.05

ゴリムマブ(％)

28(2.9)

0(0)

0.21

ウステキヌマブ(％)

33(3.4)

2(7.4)

0.32

ベドリズマブ(％)

59(6.1)

0(0)

0.06

トファチニブ(％)

36(3.7)

0(0)

0.16

生物学的製剤(％)

227(23.5)

5(18)

0.53

266(28)

5(18)

0.28

喫煙歴(％)

ステロイド強力静注

白血球系細胞除去

法(％)

法(％)

チオプリン製剤(％)

UC, ulcerative colitis; PSC, primary sclerosing cholangitis;

TNF, tumor necrosis factor

58

表 8. 当院 UC 症例の治療内容に関する多変量解析

ステロイド強力静注

環境要因

男 :

561

女 :

432

Yes: 197

オッズ比

95％信頼区間

市販後診断

強力静注

オッズ比

95％信頼区間

0.60

0.71-1.22

1.69

1.22-2.34

reference

Yes: 246

1.21

No: 747

reference

Yes: 167

0.91

0.0015

0.88-1.67

p値

0.63-1.33

1.15-2.38

0.21

0.11-0.40

＜0.0001

reference

Yes: 344

0.88-1.96

0.18

reference

1.31

0.6

reference

0,007

1.66

1.31

0.24

喫煙者

ステロイド

手術

reference

0.93

No: 796

No: 826

p値

reference

高齢者

生物学的製剤

インフリキシマブ

993

性別

0.43-4.00

0.63

reference

3.04

2.23-4.36

＜0.0001

No: 649

reference

Yes: 232

生物学的製剤

No: 761

Yes: 27

PSC 合

No: 966

0.33

0.11-0.96

reference

1.31

0.04

0.44-4.00

0.63

reference

UC, ulcerative colitis; PSC, primary sclerosing cholangitis

59

オッズ

95％信頼区間

referenc

0.04

0.68

0.47-0.98

2.46

referenc

0.88

referenc

0.61

referenc

1.62-3.71

6.25

4.31-9.05

referenc

1.49

referenc

0.87

referenc

p値

＜0.0001

0.55-1.39

0.57

0.36-1.05

0.08

＜0.0001

0.98-2.27

0.06

0.23-3.24

0.87

表 9. 当院の PSC 症例と PSC-UC 症例の背景比較

PSC

別(男

診断

PSC-UC

p値

17

31

9/8

21/10

0.31

42.6±19.3

29.7±12.1

0.008

40 歳未満

9(53)

24(77)

40 歳以上 60 歳未満

4(24)

7(23)

60 歳以上

4(24)

0(0)

5-ASA

ステロイド

0(0)

0(0)

0(0)

20(65)

19(61)

13(41)

<0.0001

<0.0001

0.0002

生物学的製剤

0(0)

5(10.4)

0.03

手術歴

0(0)

2(6.4)

0.18

/ 女 )

年齢(平均±標準偏差)

年齢

0.0095

UC と

の加

あり

UC の表現型

<0.0001

右側

0(0)

左側

0(0)

8(26)

0(0)

13(41)

0(0)

2(6.5)

7(41)

10(32)

0.54

ドレナージ術

4(24)

4(13)

0.35

UCDA 内服

16(94)

27(87)

0.42

全結

不明

移植後 or 待

状態

8(26)

死亡確認

6(35)

8(26)

0.49

1(5.9)

5(16.1)

0.28

1(5.9)

2(6.5)

0.94

0(0)

1(3.2)

0.35

嚢癌

0(0)

1(3.2)

0.35

0(0)

1(3.2)

0.35

肝内

UC, ulcerative colitis; PSC, primary sclerosing cholangitis; UCDA, ursodeoxycholic acid

60

表 10. 当院 PSC 症例の臨床イベントに関する多変量解析

環境要因

オッズ比

48

reference

: 18

0.74

0.14-4.04

3.44

0.26-45.1

40 歳以上 60 歳未満：11

60 歳以上：4

UCDA 内服

ドレナージ

術の有無

UC 合

95％信頼区間

: 30

40 歳未満：33

年齢

ドレナージ術

p値

0.73

オッズ比

reference

0.35

reference

2.37

0.28－20.2

0.28

0.024ー3.17

0.10-90.4

Yes: 43

0.45

0.03-6.25

No: 5

reference

0.52

1.75

0.07－44.2

0.55

No: 40

reference

reference

0.30

0.99

0.73

reference

16.3

No: 17

0.43

0.08-4.06

0.57

29373474

reference

UC, ulcerative colitis; PSC, primary sclerosing cholangitis; UCDA, ursodeoxycholic acid

61

オッズ比

95％信頼区間

reference

p値

0.77

0.80

0.07-3.36

2.31

0.40-13.2

0.35

4.3669e-8

0.99

0.61

0.07－5.42

reference

10271544

Yes: 8

0.56

p値

reference

3.05

Yes: 31

95％信頼区間

肝移植術

0.66

reference

1.58-168

0.02

4.30

0.69－27.1

0.12

reference

0.99

0.38

reference

0.09－1.65

0.19

...