This study included a total of 767 BCW with complete data. Among them, there were 217 patients in the initially diagnosed group, 184 patients in the chemotherapy group, and 366 patients in the follow-up group, with an average follow-up time of 30 months. The anthropometric measurements, laboratory test results and other baseline characteristics of initially diagnosed group and chemotherapy group were presented in Table 1. There was no significant difference in the age and BMI of initially diagnosed group and chemotherapy group (50.9 ± 11.3 vs. 50.2 ± 9.6 vs. 51.33 ± 10.4 years, 23.5 ± 3.1 vs. 24.0 ± 3.0 vs. 23.5 ± 2.9 kg/m2). Compared to initially diagnosed group, liver enzymes (ALT, AST, GGT), total cholesterol and fasting glucose level significantly elevated in chemotherapy group, which remained high in follow-up group. Especially, the average CAP value indicating steatosis was higher in chemotherapy group (258.4 ± 27.7) and follow-up group (254.0 ± 31.7) compare to initially diagnosed group (247.3 ± 31.1, P < 0.05). A total of 513 breast cancer patients (irrespective of treatment stage) with complete data on their age, BMI, waist circumference, ALT, AST, GGT, ALP, total cholesterol, triglycerides, LDL-C, HDL-C, fasting glucose, hs-CRP were screened for multivariate analysis (Supplement Table 1). Compared to non-HS subjects, patients with HS had higher age, BMI, waist circumference, ALT, AST, GGT, ALP, total cholesterol, triglycerides, LDL-C, fasting glucose, hs-CRP and lower HDL-C level (P < 0.05). The variables used for analysis included age, BMI, waist circumference, ALT, AST, GGT, ALP, total cholesterol, triglycerides, LDL-C, HDL-C, fasting glucose, hs-CRP. Total cholesterol and HDL-C were removed from the model after being tested for multicollinearity. The logistic model obtained was of statistical significance (χ2 = 255.551, p < 0.001) and percentage accuracy in classification (PAC) was 81.7%. By contrast, the logistic model for US-diagnosed HS had lower PAC (75.6%). After adjusting for age, BMI and other factors, binary logistic regression analysis determined that the independent influencing factors of HS based on USE were gender, BMI, GGT and Triglycerides (P < 0.05). For every 1-unit increase in BMI, GGT, and Triglycerides, the risk of HS increases by 66.3%, 2.4%, and 147.4%, respectively.
Table 1
Baseline characteristics of Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
Variable
|
Initially diagnosed group (n = 217)
|
Chemotherapy group
(n = 184)
|
Follow-up group
(n = 366)
|
P value
|
Age, years
|
50.9 ± 11.3
|
50.2 ± 9.6
|
51.33 ± 10.4
|
0.09
|
BMI, kg/m2
|
23.5 ± 3.1
|
24.0 ± 3.0
|
23.5 ± 2.9
|
0.159
|
Waist circumference, cm
|
85.0 ± 10.0
|
85.2 ± 8.4
|
81.8 ± 8.3
|
< 0.0001
|
Alb, g/L
|
42.2 ± 3.2
|
40.1 ± 4.8
|
48.1 ± 3.3
|
< 0.0001
|
ALT, U/L
|
13.0 (8.0)
|
27.0 (20.0)
|
18.0 (12.0)
|
< 0.0001
|
AST, U/L
|
16.0 (6.0)
|
23.0 (12.0)
|
21.0 (8.0)
|
< 0.0001
|
GGT, U/L
|
15.0 (13.0)
|
22.0 (21.0)
|
21.0 (20.0)
|
0.001
|
ALP, U/L
|
63.2 ± 21.4
|
66.5 ± 21.1
|
75.0 ± 26.1
|
< 0.0001
|
Total cholesterol, mmol/L
|
4.4 ± 0.9
|
5.0 ± 1.1
|
4.7 ± 1.0
|
< 0.0001
|
Triglycerides, mmol/L
|
1.0 (0.7)
|
1.0 (1.0)
|
1.4 (1.0)
|
< 0.0001
|
LDL-C, mmol/L
|
2.87 ± 0.8
|
3.2 ± 1.0
|
2.8 ± 1.0
|
< 0.0001
|
HDL-C, mmol/L
|
1.3 ± 0.3
|
1.3 ± 0.4
|
1.4 ± 0.4
|
< 0.0001
|
Fasting glucose, mmol/L
|
5.2 ± 1.0
|
6.6 ± 2.6
|
5.9 ± 1.1
|
< 0.0001
|
HbA1c, %
|
5.6 ± 0.9
|
5.8 ± 1.0
|
5.8 ± 0.9
|
0.447
|
hs-CRP, mg/L
|
0.7 (1.2)
|
1.0 (1.8)
|
0.6 (0.9)
|
0.001
|
LSM
|
6.3 ± 1.8
|
6.7 ± 2.1
|
6.6 ± 2.4
|
0.284
|
CAP
|
247.3 ± 31.1
|
258.4 ± 27.7
|
254.0 ± 31.7
|
0.001
|
Data are mean ± SD or median (IQR). P values were derived from Student t-test, the Mann-Whitney U test or chi-square test.
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; Alb, plasma albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; HDL, high-density lipoprotein-cholesterol; LDL, low-density lipoprotein-cholesterol; HbA1c, hemoglobin A1c; hs-CRP, plasma high-sensitivity C-reactive protein; LSM, liver stiffness measurement; CAP, controlled attenuation parameter.
|
The prevalence of HS detected by US was significantly higher in the chemotherapy group than in the primary diagnosis group (36.7% versus 21.7%, P < 0.05), and increased to 38.0% in the follow-up patients (Table 2). USE had a higher rate of HS detection compared to US. USE-diagnosed HS increased to 78.6% in the chemotherapy group compared to the first-diagnosed group (60.4%, p < 0.05), and decreased in the follow-up group (68%), mainly in mild-to-moderate HS. After grading by UAP measurement, moderate to severe HS cases accounted for 29.5%, 42.8% and 39.2%, respectively in initially diagnosed, chemotherapy and follow-up groups. BMI subgroups showed that BMI ≥ 23 had a higher HS prevalence, 86.7%, 91.8% and 86.5% in the three groups (Table 3). HS prevalence was significantly higher in the chemotherapy group of patients with normal or low BMI than in the first diagnosis group (58.3% vs. 31.7%, p < 0.05), and decreased in the follow-up group (45.1%, p > 0.05). Age stratification showed that menopausal patients ≥ 60 years of age had a higher prevalence of HS, 82.6%, 83.3% and 77.9% in the three groups, respectively (Table 3). The prevalence of HS was significantly higher in the chemotherapy group than in the first diagnosis group in patients younger than 60 years of age (77.8% vs. 54.7%, p < 0.05), with a significant decrease in the follow-up group (65.3%, p < 0.05).
Table 2
Prevalence of hepatic steatosis (HS) based on US and USE in Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
|
US-diagnosed HS
|
|
USE-diagnosed HS
|
|
Grading
|
|
|
|
Mild
|
moderate
|
severe
|
Initially diagnosed group
|
43/198
(21.7%)
|
|
131/217
(60.4%)
|
|
67
(30.9%)
|
48
(22.1%)
|
16
(7.4%)
|
Chemotherapy group
|
61/166
(36.7%)*
|
|
143/182
(78.6%)*
|
|
65
(35.7%)
|
63
(34.6%)*
|
15
(8.2%)
|
Follow-up group
|
139/366
(38.0%)†
|
|
246/362
(68.0%)§
|
|
104
(28.7%)
|
105
(29.0%)
|
37
(10.2%)
|
HS, hepatic steatosis; US, ultrasound; USE, ultrasound elastography; BCW, breast cancer women. *: significant statistic difference between initially diagnosed group and chemotherapy group (P value < 0.05); †: significant statistic difference between initially diagnosed group and follow-up group (P < 0.05); §: statistic difference between chemotherapy group and follow-up group (P value < 0.05).
|
Table 3
Age and BMI stratification of hepatic steatosis (HS) diagnosed by USE in Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
Stratification
|
Initially diagnosed group
|
Chemotherapy group
|
Follow-up group
|
BMI, kg/m2
|
|
|
|
< 23
|
33/104
(31.7%)
|
42/72
(58.3%)*
|
73/162
(45.1%)
|
≥ 23
|
98/113
(86.7%)
|
101/110
(91.8%)
|
173/200
(86.5%)
|
Age, years
|
|
|
|
< 60
|
93/170
(54.7%)
|
123/158
(77.8%)*
|
186/285
(65.3%)§
|
≥ 60
|
38/46
(82.6%)
|
20/24
(83.3%)
|
60/77
(77.9%)
|
HS, hepatic steatosis; US, ultrasound; USE, ultrasound elastography; BCW, breast cancer women. *: significant statistic difference between initially diagnosed group and chemotherapy group (P value < 0.05); †: significant statistic difference between initially diagnosed group and follow-up group (P < 0.05); §: statistic difference between chemotherapy group and follow-up group (P value < 0.05).
|
In the initially diagnosed group, 155 BCW were US negative patients, whereas 51% were further diagnosed with HS by USE (Table 4). Most of these are mild (70.0%) and moderate (26.6%) cases. Similarly, 70% and 51.3% BCW were US-negative but USE-positive in chemotherapy group, of which mild to moderate cases accounted for 94.6% and 91.3% respectively.
Table 4
Comparison of diagnosis of hepatic steatosis (HS) by US and USE in Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
|
US
|
USE
|
|
Grading
|
|
|
Negative
|
Positive
|
|
Mild
|
moderate
|
severe
|
Initially diagnosed group
|
Negative (155)
|
76
(49.0%)
|
79
(51.0%)
|
|
55
(35.5%)
|
21
(13.5%)
|
3
(1.9%)
|
Positive (43)
|
1
(2.3%)
|
42
(97.7%)
|
|
9
(20.9%)
|
21
(48.8%)
|
12
(27.9%)
|
Chemotherapy group
|
Negative (105)
|
31
(29.5%)
|
74
(70.5%)
|
|
48
(45.7%)
|
22
(21.0%)
|
4
(3.8%)
|
Positive (59)
|
2
(3.4%)
|
57
(96.6%)
|
|
12
(20.3%)
|
36
(61.0%)
|
9
(15.3%)
|
Follow-up group
|
Negative (224)
|
109
(48.7%)
|
115
(51.3%)
|
|
178
(36.8%)
|
80
(16.5%)
|
10
(2.1%)
|
Positive (59)
|
7
(5.1%)
|
131
(94.9%)
|
|
50
(20.8%)
|
125
(52.1%)
|
55
(22.9%)
|
HS, hepatic steatosis; US, ultrasound; USE, ultrasound elastography; BCW, breast cancer women.
|
The prevalence of MAFLD based on US in chemotherapy group was significantly higher than in the initially diagnosed group (33.1% vs. 20.4%, P < 0.05), and the proportion increased to 34.7% in follow-up group (Table 5). With the implementation of USE, MAFLD prevalence increased to 68.1% in the chemotherapy group compared to the initially diagnosed group (49.8%, p < 0.05), but decreased in the follow-up group to 59.1%. Moderate to severe HS cases accounted for 28.6%, 41.2%, and 37.1% in the initially diagnosed, chemotherapy, and follow-up groups, respectively. The different BMI categories revealed that overweight or obese patients had a greater occurrence of MAFLD, reaching as high as 91.8% in the chemotherapy group (Table 6). Comparatively, the chemotherapy group had a significantly higher prevalence of MAFLD than the initially diagnosed group among patients with normal or low BMI (31.9% vs. 9.6%, p < 0.05), and this occurrence decreased in the follow-up group (25.9%) but remained higher than in the first-diagnosis group (p < 0.05). When considering age, menopausal patients aged 60 years or older exhibited a higher prevalence of MAFLD. In patients younger than 60 years of age, the chemotherapy group had a significantly higher prevalence of MAFLD compared to the initially diagnosed group (67.1% vs. 42.9%, p < 0.05), which decreased significantly in the follow-up group (55.4%, p < 0.05), but still remained higher than in the first-diagnosis group (p < 0.05).
Table 5
Prevalence of MAFLD based on US and USE in Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
|
US-diagnosed MAFLD
|
|
USE-diagnosed MAFLD
|
|
USE-grading
|
|
|
|
|
Mild
|
moderate
|
severe
|
|
Initially diagnosed group
|
42/206
(20.4%)
|
|
108/217
(49.8%)
|
|
46
(21.2%)
|
46
(21.2%)
|
16
(7.4%)
|
|
Chemotherapy group
|
57/172
(33.1%)*
|
|
124/182
(68.1%)*
|
|
49
(26.9%)
|
60
(33.0%)*
|
15
(8.2%)
|
|
Follow-up group
|
127/366
(34.7%)†
|
|
215/364
(59.1%)
|
|
80
(22.0%)
|
98
(26.9%)
|
37
(10.2%)
|
|
MAFLD, metabolic associated fatty liver disease; US, ultrasound; USE, ultrasound elastography; BCW, breast cancer women. *: significant statistic difference between initially diagnosed group and chemotherapy group (P value < 0.05); †: significant statistic difference between initially diagnosed group and follow-up group (P < 0.05); §: statistic difference between chemotherapy group and follow-up group (P value < 0.05).
|
Table 6
Age and BMI stratification of MAFLD diagnosed by USE in Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
Stratification
|
Initially diagnosed group
|
Chemotherapy group
|
Follow-up group
|
BMI, kg/m2
|
|
|
|
< 23
|
10/104
(9.6%)
|
23/72
(31.9%)*
|
42/162
(25.9%)†
|
≥ 23
|
98/113
(86.7%)
|
101/110
(91.8%)
|
173/200
(86.5%)
|
Age, years
|
|
|
|
< 60
|
73/170
(42.9%)
|
106/158
(67.1%)*
|
158/285
(55.4%)†§
|
≥ 60
|
35/46
(76.1%)
|
18/24
(75.0%)
|
57/77
(74.0%)
|
MAFLD, metabolic associated fatty liver disease; US, ultrasound; USE, ultrasound elastography; BCW, breast cancer women. *: significant statistic difference between initially diagnosed group and chemotherapy group (P value < 0.05); †: significant statistic difference between initially diagnosed group and follow-up group (P < 0.05); §: statistic difference between chemotherapy group and follow-up group (P value < 0.05).
|
The prevalence of liver function abnormalities in chemotherapy group was higher than in the initially diagnosed group (28.3% vs. 7.5%, P < 0.05), which was more evident in the US-diagnosed HS patients (38.6% vs. 16.3%, P < 0.05). (Table 7) By contrast, the proportion decreased in USE-diagnosed HS patients (29.6% vs. 11.5%, P < 0.05). In the chemotherapy group, about half of severe HS patients (57.1%) were diagnosed with liver function abnormalities, compared to 25% in the initially diagnosed group, which remained high in follow-up group (50%). It was also shown that the prevalence of liver function abnormalities in the chemotherapy group with MAFLD based on the US was higher than in the initial diagnosis group (41.5% vs. 16.7%, P < 0.05), and declined to 31.5% in follow-up group. The results were similar in USE-diagnosed MAFLD patients (12.1%, 32.5% vs. 23.7%, P < 0.05) in initially diagnosed, chemotherapy and follow-up groups.
Table 7
Prevalence of liver function abnormalities (LA) among Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
|
LA
|
LA in US-diagnosed HS
|
LA in USE-diagnosed HS
|
Grading
|
|
LA in US-diagnosed MAFLD
|
LA in USE-diagnosed MAFLD
|
|
|
|
|
Mild
|
moderate
|
severe
|
|
|
|
Initially diagnosed group
|
16/213
(7.5%)
|
7/43
(16.3%)
|
15/130
(11.5%)
|
5/67
(7.5%)
|
6/47
(12.8%)
|
4/16
(25.0%)
|
|
7/42
(16.7%)
|
13/107
(12.1%)
|
Chemotherapy group
|
49/173
(28.3%)*
|
22/57
(38.6%)*
|
40/135
(29.6%)*
|
13/63
(20.6%)
|
19/58
(32.8%)
|
8/14
(57.1%)
|
|
22/53
(41.5%)*
|
38/117
(32.5%)*
|
Follow-up group
|
70/353
(19.8%)†
|
42/135
(31.1%)
|
55/242
(22.7%)†
|
11/103
(10.7%)
|
26/103
(25.2%)
|
18/36
(50.0%)
|
|
39/124
(31.5%)†
|
50/211
(23.7%)†
|
LA, liver function abnormalities; HS, hepatic steatosis; MAFLD, metabolic associated fatty liver disease; US, ultrasound; USE, ultrasound elastography; *: significant statistic difference between initially diagnosed group and chemotherapy group (P value < 0.05); †: significant statistic difference between initially diagnosed group and follow-up group (P < 0.05); §: statistic difference between chemotherapy group and follow-up group (P value < 0.05).
|
The prevalence of MetS were similar in three BCW groups (26.7% vs. 28.3% vs. 31.4%, Table 8). However, 76.7% patients were diagnosed with MetS in US-diagnosed HS patients within initially diagnosed group, this number declined to 42.6% and 54% in chemotherapy and follow-up groups. The percentage of MetS in BCW with severe HS accounted for 75.0%, 66.7% and 59.5% respectively in initially diagnosed group, chemotherapy group and follow-up group. The MetS prevalence was higher in patients with US-diagnosed MAFLD in three groups (78.6% vs. 45.6% vs. 59.1%).
Table 8
Prevalence of metabolic syndrome (MetS) among Chinese breast cancer woman in the initially diagnosed, during chemotherapy and follow-up stages
|
MetS
|
MetS in US-diagnosed HS
|
MetS in USE-diagnosed HS
|
Grading
|
|
MetS in US-diagnosed MAFLD
|
MetS in USE-diagnosed MAFLD
|
|
|
|
|
Mild
|
moderate
|
severe
|
|
|
|
Initially diagnosed group
|
58/217
(26.7%)
|
33/43
(76.7%)
|
53/131
(40.5%)
|
16/67
(23.9%)
|
25/48
(52.1%)
|
12/16
(75.0%)
|
|
33/42
(78.6%)
|
53/108
(49.1%)
|
Chemotherapy group
|
54/184
(28.3%)
|
26/61
(42.6%)*
|
48/143
(33.6%)
|
16/65
(24.6%)
|
22/63
(34.9%)
|
10/15
(66.7%)
|
|
26/57
(45.6%)*
|
48/124
(38.7%)
|
Follow-up group
|
115/366
(31.4%)
|
75/139
(54.0%)†
|
105/246
(42.7%)
|
26/104
(25.0%)
|
57/105
(54.3%)§
|
22/37
(59.5%)
|
|
75/127
(59.1%)
|
105/215
(48.8%)
|
MetS, metabolic syndrome; HS, hepatic steatosis; MAFLD, metabolic associated fatty liver disease; US, ultrasound; USE, ultrasound elastography; *: significant statistic difference between initially diagnosed group and chemotherapy group (P value < 0.05); †: significant statistic difference between initially diagnosed group and follow-up group (P < 0.05); §: statistic difference between chemotherapy group and follow-up group (P value < 0.05).
|