Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 11, Number 4, August 2018, pages 309-316

Association Between Vitamin D Levels and Treatment Response to Direct-Acting Antivirals in Chronic Hepatitis C: A Real-World Study

**Table 1.** Demographic and Clinical Characteristics of Patients at Baseline With Treatment Regimen
Characteristics	All patients (N = 291)	Vitamin D status	P-value
Data presented as number/total number (percent). *Statistically significant P-values. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; MELD: model for end-stage liver disease; ALT: alanine transaminase; AST: aspartate aminotransferase; CAD: coronary artery disease; CKD: chronic kidney disease.
Age (years)	60.35 ± 10.407	59.52 ± 11.597	61.33 ± 8.947	60.22 ± 10.433	0.437
Gender					0.683
Male	179 (61.5%)	66 (58.4%)	67 (63.8%)	46 (63%)
Female	112 (38.5%)	47 (41.6%)	38 (36.2%)	27 (37%)
Race					0.051
White	43 (14.8%)	9 (8%)	24 (22.9%)	10 (13.7%)
Black	200 (68.7%)	84 (74.3%)	66 (62.9%)	50 (68.5%)
Asian	1 (0.3%)	1 (0.9%)	0	0
Hispanic	18 (6.2%)	5 (4.4%)	9 (8.6%)	4 (5.5%)
Other	29 (10%)	14 (12.4%)	6 (5.7%)	9 (12.3%)
BMI (kg/m²)	28. 202 ± 5.6422	28.951 ± 5.7738	27.203 ± 5.0969	28.478 ± 6.0353	0.065
HCV genotype					0.073
1a	172 (59.1%)	67 (59.3%)	67 (63.8%)	38 (52.1%)
1b	74 (25.4%)	21 (18.6%)	31 (29.5%)	22 (30.1%)
2	13 (4.5%)	7 (6.2%)	2 (1.9%)	4 (5.5%)
3	11 (3.8%)	5 (4.4%)	3 (2.9%)	3 (4.1%)
4	21 (7.2%)	13 (11.5%)	2 (1.9%)	6 (8.2%)
HCV RNA (IU/mL)					0.207
< 800,000	88 (30.2%)	30 (26.5%)	30 (28.6%)	28 (38.4%)
≥ 800,000	203 (69.8%)	83 (73.5%)	75 (71.4%)	45 (61.6%)
Prior treatment					0.538
Naive	231 (79.4%)	86 (76.1%)	86 (81.9%)	59 (80.8%)
Experienced	60 (20.6%)	27 (23.9%)	19 (18.1%)	14 (19.2%)
Treatment regimen					0.767
LDV/SOF	184 (63.2%)	68 (60.2%)	70 (66.7%)	46 (63%)
OBV/PTV/r + DSV	59 (20.3%)	25 (22.1%)	21 (20%)	13 (17.8%)
SOF/VEL	48 (16.5%)	20 (17.7%)	14 (13.3%)	14 (19.2%)
Comorbidities
Diabetes	94 (32.3%)	38 (33.6%)	33 (31.4%)	23 (31.5%)	0.928
Hypertension	146 (50.2%)	60 (53.1%)	49 (46.7%)	37 (50.7%)	0.634
CAD	26 (8.9%)	11 (9.7%)	8 (7.6%)	7 (9.6%)	0.839
CKD	25 (8.6%)	15 (13.3%)	7 (6.7%)	3 (4.1%)	0.063
Cirrhosis					< 0.001*
Absent	220 (75.6%)	83 (73.5%)	68 (64.8%)	69 (94.5%)
Present	71 (24.4%)	30 (26.5%)	37 (35.2%)	4 (5.5%)
MELD score					0.052
< 10	207 (71.1%)	75 (66.4%)	72 (68.6%)	60 (82.2%)
≥ 10	84 (28.9%)	38 (33.6%)	33 (31.4%)	13 (17.8%)
Laboratory tests
Hemoglobin (g/dL)	13.236 ± 1.5712	13.165 ± 1.5414	13.470 ± 1.6247	13.011 ± 1.5151	0.131
Platelets (×10³/mL)	194.19 ± 77.349	190.57 ± 73.014	191.09 ± 84.270	204.26 ± 73.552	0.439
Albumin (g/dL)	4.143 ± 5.4187	4.015 ± 3.9245	4.563 ± 8.0412	3.738 ± 0.6780	0.578
AST (IU/L)	63.02 ± 76.095	68.28 ± 91.076	67.38 ± 79.871	48.59 ± 30.368	0.173
ALT (IU/L)	65.14 ± 99.580	77.24 ± 150.455	61.74 ± 45.565	51.29 ± 35.885	0.202
Bilirubin (mg/dL)	0.903 ± 0.7806	0.905 ± 0.8913	1.047 ± 0.8281	0.693 ± 0.3913	0.012*

Table 1. Demographic and Clinical Characteristics of Patients at Baseline With Treatment Regimen

Characteristics

All patients (N = 291)

Vitamin D status

P-value

Deficiency (< 20 ng/mL) (N = 113)

Insufficiency (20 - 29.9 ng/mL) (N = 105)

Normal (≥ 30 ng/mL) (N = 73)

Data presented as number/total number (percent). *Statistically significant P-values. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; MELD: model for end-stage liver disease; ALT: alanine transaminase; AST: aspartate aminotransferase; CAD: coronary artery disease; CKD: chronic kidney disease.

Age (years)

60.35 ± 10.407

59.52 ± 11.597

61.33 ± 8.947

60.22 ± 10.433

0.437

Gender

0.683

Male

179 (61.5%)

66 (58.4%)

67 (63.8%)

46 (63%)

Female

112 (38.5%)

47 (41.6%)

38 (36.2%)

27 (37%)

Race

0.051

White

43 (14.8%)

9 (8%)

24 (22.9%)

10 (13.7%)

Black

200 (68.7%)

84 (74.3%)

66 (62.9%)

50 (68.5%)

Asian

1 (0.3%)

1 (0.9%)

Hispanic

18 (6.2%)

5 (4.4%)

9 (8.6%)

4 (5.5%)

Other

29 (10%)

14 (12.4%)

6 (5.7%)

9 (12.3%)

BMI (kg/m²)

28. 202 ± 5.6422

28.951 ± 5.7738

27.203 ± 5.0969

28.478 ± 6.0353

0.065

HCV genotype

0.073

172 (59.1%)

67 (59.3%)

67 (63.8%)

38 (52.1%)

74 (25.4%)

21 (18.6%)

31 (29.5%)

22 (30.1%)

13 (4.5%)

7 (6.2%)

2 (1.9%)

4 (5.5%)

11 (3.8%)

5 (4.4%)

3 (2.9%)

3 (4.1%)

21 (7.2%)

13 (11.5%)

2 (1.9%)

6 (8.2%)

HCV RNA (IU/mL)

0.207

< 800,000

88 (30.2%)

30 (26.5%)

30 (28.6%)

28 (38.4%)

≥ 800,000

203 (69.8%)

83 (73.5%)

75 (71.4%)

45 (61.6%)

Prior treatment

0.538

Naive

231 (79.4%)

86 (76.1%)

86 (81.9%)

59 (80.8%)

Experienced

60 (20.6%)

27 (23.9%)

19 (18.1%)

14 (19.2%)

Treatment regimen

0.767

LDV/SOF

184 (63.2%)

68 (60.2%)

70 (66.7%)

46 (63%)

OBV/PTV/r + DSV

59 (20.3%)

25 (22.1%)

21 (20%)

13 (17.8%)

SOF/VEL

48 (16.5%)

20 (17.7%)

14 (13.3%)

14 (19.2%)

Comorbidities

Diabetes

94 (32.3%)

38 (33.6%)

33 (31.4%)

23 (31.5%)

0.928

Hypertension

146 (50.2%)

60 (53.1%)

49 (46.7%)

37 (50.7%)

0.634

CAD

26 (8.9%)

11 (9.7%)

8 (7.6%)

7 (9.6%)

0.839

CKD

25 (8.6%)

15 (13.3%)

7 (6.7%)

3 (4.1%)

0.063

Cirrhosis

< 0.001*

Absent

220 (75.6%)

83 (73.5%)

68 (64.8%)

69 (94.5%)

Present

71 (24.4%)

30 (26.5%)

37 (35.2%)

4 (5.5%)

MELD score

0.052

< 10

207 (71.1%)

75 (66.4%)

72 (68.6%)

60 (82.2%)

≥ 10

84 (28.9%)

38 (33.6%)

33 (31.4%)

13 (17.8%)

Laboratory tests

Hemoglobin (g/dL)

13.236 ± 1.5712

13.165 ± 1.5414

13.470 ± 1.6247

13.011 ± 1.5151

0.131

Platelets (×10³/mL)

194.19 ± 77.349

190.57 ± 73.014

191.09 ± 84.270

204.26 ± 73.552

0.439

Albumin (g/dL)

4.143 ± 5.4187

4.015 ± 3.9245

4.563 ± 8.0412

3.738 ± 0.6780

0.578

AST (IU/L)

63.02 ± 76.095

68.28 ± 91.076

67.38 ± 79.871

48.59 ± 30.368

0.173

ALT (IU/L)

65.14 ± 99.580

77.24 ± 150.455

61.74 ± 45.565

51.29 ± 35.885

0.202

Bilirubin (mg/dL)

0.903 ± 0.7806

0.905 ± 0.8913

1.047 ± 0.8281

0.693 ± 0.3913

0.012*

**Table 2.** Demographic and Clinical Characteristics of Patients at Baseline by Treatment Response
Characteristics	All patient (N = 291)	Treatment response	P-value
Data presented as number/total number (percent). *Statistically significant P-values. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; MELD: model for end-stage liver disease; ALT: alanine transaminase; AST: aspartate aminotransferase; CAD: coronary artery disease; CKD: chronic kidney disease.
Age (years)	60.35 ± 10.407	61.47 ± 12.403	60.29 ± 10.310	0.723
Age group				0.680
< 65	189 (64.9%)	9 (60%)	180 (65.2%)
≥ 65	102 (35.1%)	6 (40%)	96 (34.8%)
Sex				0.334
Male	179 (61.5%)	11 (73.3%)	168 (60.9%)
Female	112 (38.5%)	4 (26.7%)	108 (39.1%)
BMI (kg/m²)	28. 202 ± 5.6422	26.147 ± 4.8868	28.313 ± 5.6667	0.148
BMI (kg/m²)				0.756
< 30	183 (62.9%)	10 (66.7%)	173 (62.7%)
≥ 30	108 (37.1%)	5 (33.3%)	103 (37.3%)
HCV genotype				0.285
1a	172 (59.1%)	12 (80%)	160 (58%)
1b	74 (25.4%)	1 (6.7%)	73 (26.4%)
2	13 (4.5%)	1 (6.7%)	12 (4.3%)
3	11 (3.8%)	1 (6.7%)	10 (3.6%)
4	21 (7.2%)	0	21 (7.6%)
HCV RNA (IU/mL)				0.565
< 800,000	88 (30.2%)	3 (20%)	85 (30.8%)
≥ 800,000	203 (69.8%)	12 (80%)	191 (69.2%)
Vitamin D status				0.214
Deficient (< 20 ng/mL)	113 (38.8%)	9 (60%)	104 (37.7%)
Insufficient (20 - 29.9 ng/mL)	105 (36.1%)	4 (26.7%)	101 (36.6%)
Normal (≥ 30 ng/mL)	73 (25.1%)	2 (13.3%)	71 (25.7%)
Treatment Regimen				0.802
LDV/SOF	184 (63.2%)	9 (60%)	175 (63.4%)
OBV/PTV/r + DSV	59 (20.3%)	4 (26.7%)	55 (19.9%)
SOF/VEL	48 (16.5%)	2 (13.3%)	46 (16.7%)
Prior treatment				0.521
Naive	231 (79.4%)	11 (73.3%)	220 (79.7%)
Experienced	60 (20.6%)	4 (26.7%)	56 (20.3%)
Comorbidities
Diabetes	94 (32.3%)	5 (33.3%)	89 (32.2%)	1.000
Hypertension	146 (50.2%)	7 (46.7%)	139 (50.4%)	0.780
CAD	26 (8.9%)	0	26 (9.4%)	0.377
CKD	25 (8.6%)	2 (13.3%)	23 (8.3%)	0.376
Cirrhosis				0.013*
Absent	220 (75.6%)	7 (46.7%)	213 (77.2%)
Present	71 (24.4%)	8 (53.3%)	63 (22.8%)
MELD score				0.381
< 10	207 (71.1%)	9 (60%)	198 (71.7%)
≥ 10	84 (28.9%)	6 (40%)	78 (28.3%)
Laboratory tests
Hemoglobin (g/dL)	13.236 ± 1.5712	13.627 ± 1.3828	13.215 ± 1.5803	0.324
Platelets (×1,000/mL)	194.19 ± 77.349	148.13 ± 98.694	196.69 ± 75.441	0.018*
AST (IU/L)	63.02 ± 76.095	74.40 ± 50.015	339.03 ± 4639.283	0.826
ALT (IU/L)	65.14 ± 99.580	70.93 ± 62.926	64.82 ± 101.260	0.817
Bilirubin (mg/dL)	0.903 ± 0.7806	1.333 ± 1.1896	0.880 ± 0.7482	0.165

Table 2. Demographic and Clinical Characteristics of Patients at Baseline by Treatment Response

Characteristics

All patient (N = 291)

Treatment response

P-value

No SVR 12 (N = 15)

SVR 12 (N = 276)

Age (years)

60.35 ± 10.407

61.47 ± 12.403

60.29 ± 10.310

0.723

Age group

0.680

< 65

189 (64.9%)

9 (60%)

180 (65.2%)

≥ 65

102 (35.1%)

6 (40%)

96 (34.8%)

Sex

0.334

Male

179 (61.5%)

11 (73.3%)

168 (60.9%)

Female

112 (38.5%)

4 (26.7%)

108 (39.1%)

BMI (kg/m²)

28. 202 ± 5.6422

26.147 ± 4.8868

28.313 ± 5.6667

0.148

BMI (kg/m²)

0.756

< 30

183 (62.9%)

10 (66.7%)

173 (62.7%)

≥ 30

108 (37.1%)

5 (33.3%)

103 (37.3%)

HCV genotype

0.285

172 (59.1%)

12 (80%)

160 (58%)

74 (25.4%)

1 (6.7%)

73 (26.4%)

13 (4.5%)

1 (6.7%)

12 (4.3%)

11 (3.8%)

1 (6.7%)

10 (3.6%)

21 (7.2%)

21 (7.6%)

HCV RNA (IU/mL)

0.565

< 800,000

88 (30.2%)

3 (20%)

85 (30.8%)

≥ 800,000

203 (69.8%)

12 (80%)

191 (69.2%)

Vitamin D status

0.214

Deficient (< 20 ng/mL)

113 (38.8%)

9 (60%)

104 (37.7%)

Insufficient (20 - 29.9 ng/mL)

105 (36.1%)

4 (26.7%)

101 (36.6%)

Normal (≥ 30 ng/mL)

73 (25.1%)

2 (13.3%)

71 (25.7%)

Treatment Regimen

0.802

LDV/SOF

184 (63.2%)

9 (60%)

175 (63.4%)

OBV/PTV/r + DSV

59 (20.3%)

4 (26.7%)

55 (19.9%)

SOF/VEL

48 (16.5%)

2 (13.3%)

46 (16.7%)

Prior treatment

0.521

Naive

231 (79.4%)

11 (73.3%)

220 (79.7%)

Experienced

60 (20.6%)

4 (26.7%)

56 (20.3%)

Comorbidities

Diabetes

94 (32.3%)

5 (33.3%)

89 (32.2%)

1.000

Hypertension

146 (50.2%)

7 (46.7%)

139 (50.4%)

0.780

CAD

26 (8.9%)

26 (9.4%)

0.377

CKD

25 (8.6%)

2 (13.3%)

23 (8.3%)

0.376

Cirrhosis

0.013*

Absent

220 (75.6%)

7 (46.7%)

213 (77.2%)

Present

71 (24.4%)

8 (53.3%)

63 (22.8%)

MELD score

0.381

< 10

207 (71.1%)

9 (60%)

198 (71.7%)

≥ 10

84 (28.9%)

6 (40%)

78 (28.3%)

Laboratory tests

Hemoglobin (g/dL)

13.236 ± 1.5712

13.627 ± 1.3828

13.215 ± 1.5803

0.324

Platelets (×1,000/mL)

194.19 ± 77.349

148.13 ± 98.694

196.69 ± 75.441

0.018*

AST (IU/L)

63.02 ± 76.095

74.40 ± 50.015

339.03 ± 4639.283

0.826

ALT (IU/L)

65.14 ± 99.580

70.93 ± 62.926

64.82 ± 101.260

0.817

Bilirubin (mg/dL)

0.903 ± 0.7806

1.333 ± 1.1896

0.880 ± 0.7482

0.165

**Table 3.** SVR 12 Rate in Patients Based on Vitamin D levels
Characteristics	Vitamin D level
Data presented as number/total number (percent). BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; MELD: model for end-stage liver disease; ALT: alanine transaminase; CAD: coronary artery disease; CKD: chronic kidney disease.
Overall	104/113 (92%)	N/A	101/105 (96.2%)	N/A	71/73 (97.3%)	N/A
Age		0.455		0.643		0.535
< 65	73/78 (93.6%)		62/64 (96.9%)		45/47 (95.7%)
≥ 65	31/35 (88.6%)		39/41 (95.1%)		26/26 (100%)
Sex		1.000		0.294		0.527
Male	61/66 (92.4%)		63/67 (94%)		44/46 (95.7%)
Female	43/47 (91.5%)		38/38 (100%)		27/27 (100%)
BMI (kg/m²)		0.301		0.580		1.000
< 30	59/66 (89.4%)		72/74 (97.3%)		42/43 (97.7%)
≥ 30	45/47 (95.7%)		29/31 (93.5%)		29/30 (96.7%)
HCV genotype		0.300		0.670		0.959
1a	60/67 (89.6%)		63/67 (94%)		37/38 (97.4%)
1b	21/21 (100%)		31/31 (100%)		21/22 (95.5%)
2	6/7 (85.7%)		2/2 (100%)		4/4 (100%)
3	4/5 (80%)		3/3 (100%)		3/3 (100%)
4	13/13 (100%)		2/2 (100%)		6/6 (100%)
HCV RNA (IU/mL)		0.441		1.000		1.000
< 800,000	29/30 (96.7%)		29/30 (96.7%)		27/28 (96.4%)
≥ 800,000	75/83 (90.4%)		72/75 (96%)		44/45 (97.8%)
Treatment		0.699		0.019		0.547
LDV/SOF	62/68 (91.2%)		69/70 (98.6%)		44/46 (95.7%)
OBV/PTV/r + DSV	24/25 (96%)		18/21 (85.7%)		13/13 (100%)
SOF/VEL	18/20 (90%)		14/14 (100%)		14/14 (100%)
Prior treatment		1.000		0.556		0.349
Naive	79/86 (91.9%)		83/86 (96.5%)		58/59 (98.3%)
Experienced	25/27 (92.6%)		18/19 (94.7%)		13/14 (92.9%)
Comorbidities
Diabetes	37/38 (97.4%)	0.268	30/33 (90.9%)	0.091	22/23 (95.7%)	0.534
Hypertension	57/60 (95%)	0.301	46/49 (93.9%)	0.337	36/37 (97.3%)	1.000
CAD	11/11 (100%)	0.596	8/8 (100%)	1.000	7/7 (100%)	1.000
CKD	14/15 (93.3%)	1.000	6/7 (85.7%)	0.244	3/3 (100%)	1.000
Cirrhosis		0.243		0.124		0.107
Absent	78/83 (94%)		67/68 (98.5%)		68/69 (98.6%)
Present	26/30 (86.7%)		34/37 (91.9%)		3/4 (75%)
ALT (IU/L)		0.736		0.295		1.000
< 40	43/46 (93.5%)		40/40 (100.0%)		34/35 (97.1%)
≥ 40	61/67 (91%)		61/65 (93.8%)		37/38 (97.4%)

Table 3. SVR 12 Rate in Patients Based on Vitamin D levels

Characteristics

Vitamin D level

Deficiency

Insufficiency

Normal

SVR 12

Univariate P-value

SVR 12

Univariate P-value

SVR 12

Univariate P-value

Data presented as number/total number (percent). BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; MELD: model for end-stage liver disease; ALT: alanine transaminase; CAD: coronary artery disease; CKD: chronic kidney disease.

Overall

104/113 (92%)

N/A

101/105 (96.2%)

N/A

71/73 (97.3%)

N/A

Age

0.455

0.643

0.535

< 65

73/78 (93.6%)

62/64 (96.9%)

45/47 (95.7%)

≥ 65

31/35 (88.6%)

39/41 (95.1%)

26/26 (100%)

Sex

1.000

0.294

0.527

Male

61/66 (92.4%)

63/67 (94%)

44/46 (95.7%)

Female

43/47 (91.5%)

38/38 (100%)

27/27 (100%)

BMI (kg/m²)

0.301

0.580

1.000

< 30

59/66 (89.4%)

72/74 (97.3%)

42/43 (97.7%)

≥ 30

45/47 (95.7%)

29/31 (93.5%)

29/30 (96.7%)

HCV genotype

0.300

0.670

0.959

60/67 (89.6%)

63/67 (94%)

37/38 (97.4%)

21/21 (100%)

31/31 (100%)

21/22 (95.5%)

6/7 (85.7%)

2/2 (100%)

4/4 (100%)

4/5 (80%)

3/3 (100%)

13/13 (100%)

2/2 (100%)

6/6 (100%)

HCV RNA (IU/mL)

0.441

1.000

< 800,000

29/30 (96.7%)

27/28 (96.4%)

≥ 800,000

75/83 (90.4%)

72/75 (96%)

44/45 (97.8%)

Treatment

0.699

0.019

0.547

LDV/SOF

62/68 (91.2%)

69/70 (98.6%)

44/46 (95.7%)

OBV/PTV/r + DSV

24/25 (96%)

18/21 (85.7%)

13/13 (100%)

SOF/VEL

18/20 (90%)

14/14 (100%)

Prior treatment

1.000

0.556

0.349

Naive

79/86 (91.9%)

83/86 (96.5%)

58/59 (98.3%)

Experienced

25/27 (92.6%)

18/19 (94.7%)

13/14 (92.9%)

Comorbidities

Diabetes

37/38 (97.4%)

0.268

30/33 (90.9%)

0.091

22/23 (95.7%)

0.534

Hypertension

57/60 (95%)

0.301

46/49 (93.9%)

0.337

36/37 (97.3%)

1.000

CAD

11/11 (100%)

0.596

8/8 (100%)

1.000

7/7 (100%)

1.000

CKD

14/15 (93.3%)

1.000

6/7 (85.7%)

0.244

3/3 (100%)

1.000

Cirrhosis

0.243

0.124

0.107

Absent

78/83 (94%)

67/68 (98.5%)

68/69 (98.6%)

Present

26/30 (86.7%)

34/37 (91.9%)

3/4 (75%)

ALT (IU/L)

0.736

0.295

1.000

< 40

43/46 (93.5%)

40/40 (100.0%)

34/35 (97.1%)

≥ 40

61/67 (91%)

61/65 (93.8%)

37/38 (97.4%)

**Table 4.** Association of Vitamin D Levels With Cirrhosis
Vitamin D status	Cirrhosis	Total (N = 291)	P-value
Data presented as number/total number (percent).
All patients	23.452 ± 9.0978	20.901 ± 5.7075	22.830 ± 8.4601	0.006
Deficiency (< 20 ng/mL)	83 (54.6%)	30 (88.2%)	113 (60.8%)	< 0.001
Insufficiency (20 - 29.9 ng/mL)	68 (49.6%)	37 (90.2%)	105 (59%)	< 0.001

Table 4. Association of Vitamin D Levels With Cirrhosis

Vitamin D status

Cirrhosis

Total (N = 291)

P-value

Absent (N = 220)

Present (N = 71)

Data presented as number/total number (percent).

All patients

23.452 ± 9.0978

20.901 ± 5.7075

22.830 ± 8.4601

0.006

Deficiency (< 20 ng/mL)

83 (54.6%)

30 (88.2%)

113 (60.8%)

< 0.001

Insufficiency (20 - 29.9 ng/mL)

68 (49.6%)

37 (90.2%)

105 (59%)

< 0.001

**Table 5.** Adverse Effects
Adverse effects	Vitamin D status	All patients (N = 291)	P-value
Data presented as number (percent).
Fatigue	32 (28.3%)	26 (24.8%)	23 (31.5%)	81 (27.8%)	0.608
Insomnia	3 (2.7%)	0	0	3 (1%)	0.092
Headache	5 (4.4%)	6 (5.7%)	4 (5.5%)	15 (5.2%)	0.902
Nausea	5 (4.4%)	5 (4.8%)	4 (5.5%)	14 (4.8%)	0.947
Diarrhea	1 (0.9%)	0	0	1 (0.3%)	0.454
Constipation	0	1 (1%)	1 (1.4%)	2 (0.7%)	0.499
Abdominal pain	3 (2.7%)	0	1 (1.4%)	4 (1.4%)	0.243
Skin rash	8 (7.1%)	4 (3.8%)	2 (2.7%)	14 (4.8%)	0.336
Arthralgia	4 (3.5%)	4 (3.8%)	4 (5.5%)	12 (4.1%)	0.793
Anemia	18 (15.9%)	11 (10.5%)	12 (16.4%)	41 (14.1%)	0.410

Table 5. Adverse Effects

Adverse effects

Vitamin D status

All patients (N = 291)

P-value

Deficiency (N = 113)

Insufficiency (N = 105)

Normal (N = 73)

Data presented as number (percent).

Fatigue

32 (28.3%)

26 (24.8%)

23 (31.5%)

81 (27.8%)

0.608

Insomnia

3 (2.7%)

3 (1%)

0.092

Headache

5 (4.4%)

6 (5.7%)

4 (5.5%)

15 (5.2%)

0.902

Nausea

5 (4.4%)

5 (4.8%)

4 (5.5%)

14 (4.8%)

0.947

Diarrhea

1 (0.9%)

1 (0.3%)

0.454

Constipation

1 (1%)

1 (1.4%)

2 (0.7%)

0.499

Abdominal pain

3 (2.7%)

1 (1.4%)

4 (1.4%)

0.243

Skin rash

8 (7.1%)

4 (3.8%)

2 (2.7%)

14 (4.8%)

0.336

Arthralgia

4 (3.5%)

4 (3.8%)

4 (5.5%)

12 (4.1%)

0.793

Anemia

18 (15.9%)

11 (10.5%)

12 (16.4%)

41 (14.1%)

0.410