J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 10, Number 12, December 2018, pages 904-910

Prevalence and Risk Factors of Elevated Liver Enzymes in Japanese Women With Polycystic Ovary Syndrome

Figure 1. Inclusion and exclusion flow chart. Flow chart representing the selection of subjects during the retrospective study. Data of 37,500 Japanese women were reviewed, and 184 reproductive-aged women with PCOS were identified using ICD-10 codes. After excluding 82 women (see Materials and Methods section), the remaining subjects were divided into two groups using cutoffs for ALT (19 IU/L). ICD-10: International Classification of Diseased, 10th revision, clinical modification; ALT: alanine amino transferase.

Figure 2. AUC for the prediction of elevated liver enzymes. ROC curves for BMI, blood glucose, testosterone, Model 1, and Model 2 in women with PCOS. AUC was calculated to assess overall diagnostic accuracy and to identify optimal cutoffs for risk factors for elevated liver enzymes. ROC: receiver-operating characteristics; AUC: area under the receiver-operating characteristics curve.

**Table 1.** Anthropometric, Clinical, and Biochemical Characteristics of 102 Patients With PCOS
Variables	Control group (N = 68 (66.7%))	Elevated liver enzymes group (N = 34 (33.3%))	P-value
Reported anthropometric, clinical, and biochemical characteristics of 102 PCOS patients. The normality distribution of the variables was tested using the Kolmogorov-Smirnov test. Differences between the two groups were compared with Student’s t-test for normally distributed data and the Mann-Whitney U-test for nonnormally distributed data. Continuous variables are presented as median (25 - 75 percentiles). *Reported elevated liver enzymes group was significantly different (P < 0.05) than in control group. AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; LDH: lactate dehydrogenase; BUN: blood urea nitrogen; WBC: white blood cell; LH: luteinizing hormone; FSH: follicle stimulation hormone; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio.
Age (years)	27.5 (24.0 - 32.0)	29.0 (22.8 - 32.0)	0.844
BMI (kg/m²)	20.7 (18.8 - 23.4)	25.3 (20.0 - 29.8)	0.003*
AST (IU/L)	17.0 (15.0 - 18.0)	27.5 (22.8 - 33.0)	< 0.001*
ALT (IU/L)	12.0 (11.0 - 14.8)	32.0 (23.0 - 49.5)	< 0.001*
ALP (IU/L)	154.5 (135.0 - 190.3)	197.0 (158.0 - 266.0)	0.001*
LDH (IU/L)	147.0 (132.8 - 166.5)	170.5 (141.0 - 204.0)	0.005*
T-bilirubin (mg/dL)	0.7 (0.5 - 0.9)	0.7 (0.5 - 0.9)	0.606
BUN (mg/dL)	12.0 (10.0 - 13.0)	11.0 (9.0 - 13.0)	0.218
Creatinine (mg/dL)	0.6 (0.5 - 0.7)	0.6 (0.5 - 0.7)	0.462
Blood glucose (mg/dL)	90.0 (83.0 - 96.0)	93.5 (85.3 - 111.0)	0.065
WBC (× 10⁹/L)	5.5 (4.5 - 6.6)	6.1 (4.6 - 8.4)	0.148
Hemoglobin (g/dL)	13.2 (12.3 - 13.5)	13.0 (12.2 - 14.2)	0.692
Platelets (× 10⁹/L)	231.5 (200.5 - 294.3)	244.0 (207.3 - 277.0)	0.821
LH (IU/L)	10.1 (7.0 - 16.5)	8.4 (4.5 - 11.1)	0.087
FSH (IU/L)	5.4 (4.7 - 6.8)	6.4 (4.6 - 7.6)	0.562
Prolactin (IU/L)	11.7 (7.0 - 17.2)	10.6 (8.5 - 14.5)	0.839
Estradiol (nmol/L)	39.0 (29.5 - 57.2)	34.0 (28.5 - 52.5)	0.555
Testosterone (nmol/L)	0.3 (0.2 - 0.4)	0.4 (0.2 - 0.7)	0.106
CRP (mg/dL)	0.03 (0.02 - 0.08)	0.06 (0.03 - 0.32)	0.138
NLR	1.61 (1.27 - 2.17)	1.75 (1.30 - 3.07)	0.258
PLR	0.22 (0.17 - 0.25)	0.22 (0.19 - 0.30)	0.890

Table 1. Anthropometric, Clinical, and Biochemical Characteristics of 102 Patients With PCOS

Variables

Control group (N = 68 (66.7%))

Elevated liver enzymes group (N = 34 (33.3%))

P-value

Reported anthropometric, clinical, and biochemical characteristics of 102 PCOS patients. The normality distribution of the variables was tested using the Kolmogorov-Smirnov test. Differences between the two groups were compared with Student’s t-test for normally distributed data and the Mann-Whitney U-test for nonnormally distributed data. Continuous variables are presented as median (25 - 75 percentiles). *Reported elevated liver enzymes group was significantly different (P < 0.05) than in control group. AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; LDH: lactate dehydrogenase; BUN: blood urea nitrogen; WBC: white blood cell; LH: luteinizing hormone; FSH: follicle stimulation hormone; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio.

Age (years)

27.5 (24.0 - 32.0)

29.0 (22.8 - 32.0)

0.844

BMI (kg/m²)

20.7 (18.8 - 23.4)

25.3 (20.0 - 29.8)

0.003*

AST (IU/L)

17.0 (15.0 - 18.0)

27.5 (22.8 - 33.0)

< 0.001*

ALT (IU/L)

12.0 (11.0 - 14.8)

32.0 (23.0 - 49.5)

< 0.001*

ALP (IU/L)

154.5 (135.0 - 190.3)

197.0 (158.0 - 266.0)

0.001*

LDH (IU/L)

147.0 (132.8 - 166.5)

170.5 (141.0 - 204.0)

0.005*

T-bilirubin (mg/dL)

0.7 (0.5 - 0.9)

0.606

BUN (mg/dL)

12.0 (10.0 - 13.0)

11.0 (9.0 - 13.0)

0.218

Creatinine (mg/dL)

0.6 (0.5 - 0.7)

0.462

Blood glucose (mg/dL)

90.0 (83.0 - 96.0)

93.5 (85.3 - 111.0)

0.065

WBC (× 10⁹/L)

5.5 (4.5 - 6.6)

6.1 (4.6 - 8.4)

0.148

Hemoglobin (g/dL)

13.2 (12.3 - 13.5)

13.0 (12.2 - 14.2)

0.692

Platelets (× 10⁹/L)

231.5 (200.5 - 294.3)

244.0 (207.3 - 277.0)

0.821

LH (IU/L)

10.1 (7.0 - 16.5)

8.4 (4.5 - 11.1)

0.087

FSH (IU/L)

5.4 (4.7 - 6.8)

6.4 (4.6 - 7.6)

0.562

Prolactin (IU/L)

11.7 (7.0 - 17.2)

10.6 (8.5 - 14.5)

0.839

Estradiol (nmol/L)

39.0 (29.5 - 57.2)

34.0 (28.5 - 52.5)

0.555

Testosterone (nmol/L)

0.3 (0.2 - 0.4)

0.4 (0.2 - 0.7)

0.106

CRP (mg/dL)

0.03 (0.02 - 0.08)

0.06 (0.03 - 0.32)

0.138

NLR

1.61 (1.27 - 2.17)

1.75 (1.30 - 3.07)

0.258

PLR

0.22 (0.17 - 0.25)

0.22 (0.19 - 0.30)

0.890

**Table 2.** ROC Analysis of Variables in Predicting Elevated Liver Enzymes in Women With PCOS
Variable	Cutoff	AUC	95% CI	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	PLH	NLH	DA (%)
Optimal cutoffs for anthropometric, clinical and biochemical measures in 102 patients with PCOS. Sensitivity and specificity were calculated. Two models were set up for predicting elevated liver enzymes using ROC curves to determine clinical references for early diagnosis and prevention. Model 1 included BMI ≥ 25.2 kg/m² and blood glucose ≥ 103 mg/dL, and Model 2 included BMI ≥ 25.2 kg/m², blood glucose ≥ 103 mg/dL, and testosterone ≥ 0.550 nmol/L. ROC: receiver-operating characteristics; AUC: area under the receiver-operating characteristics curve; CI: confidence interval; PPV: positive predictive value; NPV: negative predictive value; PLH: positive likelihood ratio; NLH: negative likelihood ratio; DA: diagnostic accuracy; Inf: infinity.
BMI	25.2	0.681	0.563 - 0.798	52.9	82.4	60.0	77.8	3.00	0.57	72.5
Blood glucose	103	0.639	0.483 - 0.794	40.0	94.9	72.7	82.4	7.87	0.63	81.0
Testosterone	0.550	0.627	0.422 - 0.832	38.5	87.0	62.5	71.4	2.95	0.71	69.4
Model 1	7.46	0.783	0.664 - 0.901	40.0	94.9	72.7	82.4	7.87	0.63	81.0
Model 2	17.7	0.861	0.688 - 0.999	66.7	100	100	87.0	Inf	0.33	89.7

Table 2. ROC Analysis of Variables in Predicting Elevated Liver Enzymes in Women With PCOS

Variable

Cutoff

AUC

95% CI

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

PLH

NLH

DA (%)

Optimal cutoffs for anthropometric, clinical and biochemical measures in 102 patients with PCOS. Sensitivity and specificity were calculated. Two models were set up for predicting elevated liver enzymes using ROC curves to determine clinical references for early diagnosis and prevention. Model 1 included BMI ≥ 25.2 kg/m² and blood glucose ≥ 103 mg/dL, and Model 2 included BMI ≥ 25.2 kg/m², blood glucose ≥ 103 mg/dL, and testosterone ≥ 0.550 nmol/L. ROC: receiver-operating characteristics; AUC: area under the receiver-operating characteristics curve; CI: confidence interval; PPV: positive predictive value; NPV: negative predictive value; PLH: positive likelihood ratio; NLH: negative likelihood ratio; DA: diagnostic accuracy; Inf: infinity.

BMI

25.2

0.681

0.563 - 0.798

52.9

82.4

60.0

77.8

3.00

0.57

72.5

Blood glucose

103

0.639

0.483 - 0.794

40.0

94.9

72.7

82.4

7.87

0.63

81.0

Testosterone

0.550

0.627

0.422 - 0.832

38.5

87.0

62.5

71.4

2.95

0.71

69.4

Model 1

7.46

0.783

0.664 - 0.901

40.0

94.9

72.7

82.4

7.87

0.63

81.0

Model 2

17.7

0.861

0.688 - 0.999

66.7

100

87.0

Inf

0.33

89.7