original article Wien Klin Wochenschr DOI 10.1007/s00508-015-0757-z
Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease in patients with chronic renal failure and coronary heart disease Ivana Mikolasevic · Lidija Orlic · Luka Zaputovic · Sanjin Racki · Zlatko Cubranic · Kata Anic · Bosiljka Devcic · Davor Stimac Received: 16 August 2014 / Accepted: 27 January 2015 © Springer-Verlag Wien 2015
Summary Background In recent years, nonalcoholic fatty liver disease (NAFLD) was recognized as an important factor in chronic kidney disease (CKD) pathogenesis. The concentrations of serum aminotransferases in both chronic dialysis and chronic renal failure (CRF) patients most commonly fall within the lower end of the range of normal values. The aim of the present study was to investigate the usefulness of four liver tests and four biological scores in detection of NAFLD in comparison with transient elastography (TE) findings in different groups of patients. Methods The study was cross-sectional analysis collected data from a single tertiary care center. Of 202 patents there were 52 patients with CKD, 50 patients with end-stage renal disease (ESRD) treated with haemodialysis (HD), 50 renal transplant recipients (RTRs) and 50 patients with proven coronary heart disease (CHD). Fifty sex- and age-matched individuals without NAFLD and with normal liver and kidney function tests served as controls. With the help of TE (FibroScan®, Echosense SA, Paris, France), liver stiffness was selected as the param-
eter to quantify liver fibrosis and Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis. Results According to the CAP findings 76.9 %CKD patients, 82 %HD patients, 74 %RTRs and 69.1 % CHD patients had CAP > 238 dB.m−1 and thus by definition NAFLD. We have found that ALT, AST and GGT levels were positively correlated with CAP values while ALT and AST showed positive correlation with liver stiffness acquired with TE only in CHD patients. According to TE findings APRI (AUC 0.796) and FIB-4 (AUC 0.790) scores were correlated with the presence of fibrosis, while HIS score was correlated with the presence of steatosis (AUC 0.867) only in CHD patients. Conclusion Liver tests and biological scores are not useful for NAFLD detection in CRF patients. TE with CAP provides the opportunity of noninvasive screening for NAFLD as well as liver fibrosis in patients with CRF.
I. Mikolasevic, MD PhD () · L. Orlic · S. Racki · B. Devcic Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia e-mail: [email protected]
Introduction
L. Zaputovic · Z. Cubranic Department of Cardiology, UHC Rijeka, Rijeka, Croatia K. Anic Infectious Disease Clinic, UHC Osijek, Osijek, Croatia D. Stimac Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia
13
Keywords Liver tests · Chronic kidney disease · Coronary heart disease · Nonalcoholic fatty liver disease · Transient elastography
The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is currently the most common chronic liver disease and the most common cause of abnormal liver biochemistry. NAFLD is considered to be a hepatic manifestation of metabolic syndrome (MS) and it occurs in people who do not consume significant amounts of alcohol. The current importance of NAFLD is lying in its association with atherosclerosis and increased incidence of cardiovascular disease (CVD). Insulin resistance (IR) plays an important role in the pathogenesis of NAFLD and is closely linked to MS and its manifestation: obesity, diabetes mellitus type 2,
Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease
1
original article
dyslipidemia, and hypertension [1–6]. In recent years, the evidences connecting NAFLD to chronic kidney disease (CKD) are growing. A growing numbers of data as well as recent meta-analysis by Musso et al. have shown that the presence and severity of NAFLD are associated with an increased risk and severity of CKD [6–9]. Considering the growing epidemic of NAFLD worldwide and it relationship with CVD and CKD, searching for the optimal and noninvasive method for NAFLD diagnosis has attracted the research interest. The main problem is that NAFLD usually gives no symptoms and is often first suspected in a person who is found to have elevations in liver tests that are include in routine blood test panels, such as aspartat aminotransferase (AST) or alanine aminotransferase (ALT). Increased aminotransferase levels are found in approximately half of all patients with NAFLD. It is important to note that ALT values do not correlate with histological findings. Alkaline phosphatase (ALP) can be slightly elevated. On the other hand, γ-glutamyl transferase (GGT) is frequently elevated and may be a marker of increased mortality in the general population. Today there are many non-invasive procedures that are being intensively investigated as means of detecting hepatic steatosis and fibrosis. They are based on clinical signs and symptoms, laboratory and imaging tests, as well as a combination of clinical and blood test results [1–6]. Some of the biological scores such as APRI score, Forns index, Fib-4 score, Hepatic Steatosis Index (HIS) are easily calculated and have shown themselves to be very useful in the assessment of liver fibrosis/steatosis [10]. Although today there are no clear recommendations whether liver biopsy is necessary to confirm the diagnosis of NAFLD, it still represents the current gold standard for definitive diagnosis of liver fibrosis and steatosis. It has some limitations, such as its invasive nature and is prone to significant sampling error considering the fact that the average size of biopsy is 15 mm in length, which represents only 1/50,000 the size of the liver parenchyma. Moreover, repetition of liver biopsy to monitor changes in steatosis is difficult and the use of liver biopsy is limited in patients with an increased risk of bleeding. Some data indicated that the use of some noninvasive radiographic techniques can be useful in assessment of hepatic stetatosis. Such methods are computed tomography and proton-magnetic resonance spectroscopy (H-MRS) [1–6]. On the other hand,the uses of these methods are limited by high cost, restricted availability, operator dependence and poor sensitivity. Also, by using these methods we cannot simultaneously evaluate liver fibrosis and steatosis. To overcome this shortcoming, a novel noninvasive method for assessing hepatic steatosis and fibrosis have been investigated. A novel method called transient elastography (TE) (FibroScan®) has been developed. According to many studies, TE has been shown promising results in assessment of liver fibrosis. In recent years, a novel parameter based on the properties of ultrasonic signals acquired by the TE has been intensively investigated. That novel physical parameter called Controlled Attenuation Parameter (CAP) could efficiently separate
steatosis grades. Values range from 100 to 400 dB/m. CAP being implemented on TE, both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of noninvasive methods for the management of chronic liver diseases [11–14]. According to the previous investigations, the concentrations of serum aminotransferases in both chronic dialysis and chronic renal failure (CRF) patients most commonly fall within the lower end of the range of normal values. Namely, the ALT levels are showed to be the poor predictor of hepatocellular damage in the chronic dialysis patients [15–17]. We were interested to analyze what is the usefulness of liver tests in assessment of NAFLD in different stages of CKD and patients with coronary heart disease (CHD) in comparison with TE findings. Therefore, the aim of the present study was to investigate the usefulness of four liver tests (AST, ALT, GGT and ALP) and four biological scores (HIS, APRI, Forns and FIB-4 scores) in detection of NAFLD in comparison with TE findings in different groups of patients.
Patients and methods The present study, which was conducted as a crosssectional format involved 212 patients; 55 patients with chronic kidney disease (CKD) grade III and IV, 52 patients with End-Stage renal disease (ESRD) who were treated with chronic haemodialysis (HD), 52 renal transplant recipients (RTRs) and 53 patients with coronary heart disease (CHD). Fifty sex- and age-matched individuals without NAFLD and with normal liver and kidney function tests served as controls. None of the involved patients had serological evidence of chronic hepatitis B and/or C virus infection, had a history of alcohol abuse of more than 20 g alcohol per day, had a history of drug treatment causing hepatic steatosis or had a history of gastrointestinal bypass surgery. Other types of metabolic or autoimmune liver disease were ruled out as well. Also, patients with dilated cardiomyopathy diagnosed by echocardiogram with systolic dysfunction of one or both ventricles, ejection fraction lower than 55 %, ventricular dilatation and left ventricular diastolic diameter bigger than 57 mm were excluded from the study. Due to the technical reasons (failed TE), mainly due to body mass index (BMI) > 30 kg/m2, 10 patients were excluded from the analysis. Therefore, 202 patients take a part in further analysis. CKD was defined as estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease; MDRD formula) ≤ 60 ml/min/1.73 m2 for > 3 months. The mean eGFR in CKD group of patients was 32.2 ± 13 ml/ min/1.73 m2. Fifty ESRD patients that were treated with chronic haemodialysis for at least 6 months had eGFR 7.1 kPa. Measurements were performed using the M probe (at the 3.5 MHz) on the right lobe of the liver trough intercostals spaces with the patients lying supine with the right arm placed behind the head to facilitate access to the right upper quadrant of the abdomen. The tip of the probe transducer is placed on the skin between the rib bones at the level of the right lobe of the liver where liver biopsy would be performed. These were done using only the M probe because the CAP algorithm is specific to this device. Ten successful measurements were performed on each patient and only cases with 10 successful measurements were considered as valid and were used for study analysis. Therefore, examinations with no successful measurements after ≥ 10 attempts were deemed failures. The success rate was calculated as the number of successful measurements divided by the total number of measurements. All scans were performed by the same investigator. Therefore, CAP being implemented on TE, both steatosis and fibrosis can be evaluated simultaneously. According to this evaluation, NAFLD was defined by the presence of steatosis with CAP values ≥ 238 dB.m−1 regardless of presence or absence of any stage of fibrosis [11]. The APRI, the Forns index and FIB-4 index were obtained to asses liver fibrosis, and were calculated based on the following formulas: FIB-4 = age [years] × AST/platelet count × ALT APRI = AST/platelet Forns index = 7.811 − 3.131 × ln platelet + 0.781 × ln GGT + 3.647 × ln age − 0.014 × cholesterol
13
For the assessment of liver steatosis, HIS score was obtained according to the following formula: HSI score = 8 × ALT/AST ratio + BMI + 2 (if diabetic) + 2 (if female) We compared the APRI, Forns index and FIB-4, as well as the HIS score with the presence and degree of fibrosis/ steatosis detected by FibroScan®. Patients were informed of the purpose and method of the research and the study was done in accordance with the Declaration of Helsinki. Statistical analysis of data was performed using descriptive statistics (mean and standard deviation). Categorical variables were tested by chi-square test. Testing the importance of the difference of two independent groups was performed using t-test. The Pearson or Spearman correlation coefficient was used to express correlations between variables. Discrimination was tested using the receiver operating characteristic (ROC) curves and by comparing areas under the curve (AUCs). AUCs between 0.7 and 0.8 were classified as “acceptable” and between 0.8 and 0.9 as “excellent” discrimination. P-value 7 kPa. We were interested to explore whether CHD patients with TE defined NAFLD and with normal kidney function had a higher values of four investigated liver test in comparison to other three groups of patients and control subjects. As it was shown in Table 2 CHD-NAFLD patients had statistically higher values of AST and ALT in comparison to other three groups of patients and control subjects. Also, they had statistically significant higher values of GGT in comparison with HD and RTRs groups of patients, as well as in comparison to control subjects. In the next step, we were investigated the usefulness of four liver test (AST, ALT, GGT and ALP) in assessment of NAFLD in comparison with TE findings in four groups of patients. We didn’t find any statistically significant correlation between CAP levels and investigated liver tests in CKD and HD patients as well as in RTRs. On the other hand, we have found that ALT, AST and GGT levels were
Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease
3
original article
Table 1 Demographic characteristics of analyzed patients CKD (n = 52)
HD (n = 50)
RTRs (n = 50)
CHD (n = 50)
Controls (n = 50)
66.0 ± 7.9
68.1 ± 9.6
66.4 ± 10
66.5 ± 6.3
66.1 ± 11.3
Male
27 (51.9 %)
26 (52.0 %)
26 (52.0 %)
26 (52.0 %)
26 (52.0 %)
Female
25 (48.1 %)
24 (48.0 %)
24 (48.0 %)
24 (48.0 %)
24 (48.0 %)
Characteristic Age (y) Sex, n(%)
Etiology Diabetic nephropathy
15 (28.8 %)
13 (26.0 %)
5 (10.0 %)
/
Nondiabetic nephrop
20 (38.5 %)
15 (30.0 %)
10 (20.0 %)
/
Glomerulonephritis
10 (19.2 %)
10 (20.0 %)
15 (30.0 %)
/
Polycystic kidney disease
5 (9.6 %)
5 (10.0 %)
10 (20.0 %)
/
Interstitial nephritis
0 (0 %)
2 (4.0 %)
6 (12.0 %)
/
Other
2 (3.8 %)
5 (10.0 %)
4 (8.0 %)
BMI (kg/m2)
27.2 ± 2.5
24.8 ± 3.2
26.6 ± 1.8
27.4 ± 3.3
/ 25.0 ± 1.2
Hypertension, n(%)
42 (80.8 %)
45 (90.0 %)
48 (96.0 %)
44 (88.0 %)
0
Diabetes, n(%)
30 (57.7 %)
20 (40.0 %)
10 (20.0 %)
25 (50.0 %)
0
Dyslipidemia, n(%)
45 (86.5 %)
42 (84.0 %)
41 (82.0 %)
40 (80.0 %)
0
eGFR (ml/min/1.73 m2)
32.2 ± 13.3
–
46.2 ± 19.0
69.5 ± 6.3
102.7 ± 3.0
Therapy ACE-I/ARBs, n(%)
25 (48.1 %)
22 (44.0 %)
22 (44.0 %)
26 (52.0 %)
0
CCB, n (%)
35 (83.3 %)
38 (76.0 %)
38 (76.0 %)
35 (70.0 %)
0
BB, n (%)
18 (34.6 %)
20 (40.0 %)
21 (42.0 %)
28 (56.0 %)
0
Diuretics, n (%)
12 (23.1 %)
20 (40.0 %)
18 (36.0 %)
20 (40.0 %)
0
Statins, n (%)
40 (76.9 %)
35 (70.0 %)
35 (70.0 %)
40 (80.0 %)
0
Antidiabetic drugs, n(%)
20 (38.5 %)
10 (20.0 %)
5 (10.0 %)
15 (30.0 %)
0
Insulin, n(%)
7 (13.5 %)
7 (14.0 %)
3 (6.0 %)
8 (16.0 %)
0
y years, CKD chronic kidney disease, HD hemodialysis, RTRs renal transplant recipients, CHD coronary heart disease, NAFLD non-alcoholic fatty liver disease, BMI body mass index, NS non-significant
Table 2 Comparasion of four liver test between CHD group and other three groups of patients, as well as between CHD and control subjects CHD (n = 50)
CKD (n = 52)
HD (n = 50)
RTR (n = 50)
Controls (n = 50)
p*
p**
p***
P****
AST (IU/L)
36.2 ± 12.3
20.8 ± 9.0
11.9 ± 3.8
18.4 ± 5.5
21.2 ± 1.1
Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease in patients with chronic renal failure and coronary heart disease Ivana Mikolasevic · Lidija Orlic · Luka Zaputovic · Sanjin Racki · Zlatko Cubranic · Kata Anic · Bosiljka Devcic · Davor Stimac Received: 16 August 2014 / Accepted: 27 January 2015 © Springer-Verlag Wien 2015
Summary Background In recent years, nonalcoholic fatty liver disease (NAFLD) was recognized as an important factor in chronic kidney disease (CKD) pathogenesis. The concentrations of serum aminotransferases in both chronic dialysis and chronic renal failure (CRF) patients most commonly fall within the lower end of the range of normal values. The aim of the present study was to investigate the usefulness of four liver tests and four biological scores in detection of NAFLD in comparison with transient elastography (TE) findings in different groups of patients. Methods The study was cross-sectional analysis collected data from a single tertiary care center. Of 202 patents there were 52 patients with CKD, 50 patients with end-stage renal disease (ESRD) treated with haemodialysis (HD), 50 renal transplant recipients (RTRs) and 50 patients with proven coronary heart disease (CHD). Fifty sex- and age-matched individuals without NAFLD and with normal liver and kidney function tests served as controls. With the help of TE (FibroScan®, Echosense SA, Paris, France), liver stiffness was selected as the param-
eter to quantify liver fibrosis and Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis. Results According to the CAP findings 76.9 %CKD patients, 82 %HD patients, 74 %RTRs and 69.1 % CHD patients had CAP > 238 dB.m−1 and thus by definition NAFLD. We have found that ALT, AST and GGT levels were positively correlated with CAP values while ALT and AST showed positive correlation with liver stiffness acquired with TE only in CHD patients. According to TE findings APRI (AUC 0.796) and FIB-4 (AUC 0.790) scores were correlated with the presence of fibrosis, while HIS score was correlated with the presence of steatosis (AUC 0.867) only in CHD patients. Conclusion Liver tests and biological scores are not useful for NAFLD detection in CRF patients. TE with CAP provides the opportunity of noninvasive screening for NAFLD as well as liver fibrosis in patients with CRF.
I. Mikolasevic, MD PhD () · L. Orlic · S. Racki · B. Devcic Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia e-mail: [email protected]
Introduction
L. Zaputovic · Z. Cubranic Department of Cardiology, UHC Rijeka, Rijeka, Croatia K. Anic Infectious Disease Clinic, UHC Osijek, Osijek, Croatia D. Stimac Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia
13
Keywords Liver tests · Chronic kidney disease · Coronary heart disease · Nonalcoholic fatty liver disease · Transient elastography
The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is currently the most common chronic liver disease and the most common cause of abnormal liver biochemistry. NAFLD is considered to be a hepatic manifestation of metabolic syndrome (MS) and it occurs in people who do not consume significant amounts of alcohol. The current importance of NAFLD is lying in its association with atherosclerosis and increased incidence of cardiovascular disease (CVD). Insulin resistance (IR) plays an important role in the pathogenesis of NAFLD and is closely linked to MS and its manifestation: obesity, diabetes mellitus type 2,
Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease
1
original article
dyslipidemia, and hypertension [1–6]. In recent years, the evidences connecting NAFLD to chronic kidney disease (CKD) are growing. A growing numbers of data as well as recent meta-analysis by Musso et al. have shown that the presence and severity of NAFLD are associated with an increased risk and severity of CKD [6–9]. Considering the growing epidemic of NAFLD worldwide and it relationship with CVD and CKD, searching for the optimal and noninvasive method for NAFLD diagnosis has attracted the research interest. The main problem is that NAFLD usually gives no symptoms and is often first suspected in a person who is found to have elevations in liver tests that are include in routine blood test panels, such as aspartat aminotransferase (AST) or alanine aminotransferase (ALT). Increased aminotransferase levels are found in approximately half of all patients with NAFLD. It is important to note that ALT values do not correlate with histological findings. Alkaline phosphatase (ALP) can be slightly elevated. On the other hand, γ-glutamyl transferase (GGT) is frequently elevated and may be a marker of increased mortality in the general population. Today there are many non-invasive procedures that are being intensively investigated as means of detecting hepatic steatosis and fibrosis. They are based on clinical signs and symptoms, laboratory and imaging tests, as well as a combination of clinical and blood test results [1–6]. Some of the biological scores such as APRI score, Forns index, Fib-4 score, Hepatic Steatosis Index (HIS) are easily calculated and have shown themselves to be very useful in the assessment of liver fibrosis/steatosis [10]. Although today there are no clear recommendations whether liver biopsy is necessary to confirm the diagnosis of NAFLD, it still represents the current gold standard for definitive diagnosis of liver fibrosis and steatosis. It has some limitations, such as its invasive nature and is prone to significant sampling error considering the fact that the average size of biopsy is 15 mm in length, which represents only 1/50,000 the size of the liver parenchyma. Moreover, repetition of liver biopsy to monitor changes in steatosis is difficult and the use of liver biopsy is limited in patients with an increased risk of bleeding. Some data indicated that the use of some noninvasive radiographic techniques can be useful in assessment of hepatic stetatosis. Such methods are computed tomography and proton-magnetic resonance spectroscopy (H-MRS) [1–6]. On the other hand,the uses of these methods are limited by high cost, restricted availability, operator dependence and poor sensitivity. Also, by using these methods we cannot simultaneously evaluate liver fibrosis and steatosis. To overcome this shortcoming, a novel noninvasive method for assessing hepatic steatosis and fibrosis have been investigated. A novel method called transient elastography (TE) (FibroScan®) has been developed. According to many studies, TE has been shown promising results in assessment of liver fibrosis. In recent years, a novel parameter based on the properties of ultrasonic signals acquired by the TE has been intensively investigated. That novel physical parameter called Controlled Attenuation Parameter (CAP) could efficiently separate
steatosis grades. Values range from 100 to 400 dB/m. CAP being implemented on TE, both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of noninvasive methods for the management of chronic liver diseases [11–14]. According to the previous investigations, the concentrations of serum aminotransferases in both chronic dialysis and chronic renal failure (CRF) patients most commonly fall within the lower end of the range of normal values. Namely, the ALT levels are showed to be the poor predictor of hepatocellular damage in the chronic dialysis patients [15–17]. We were interested to analyze what is the usefulness of liver tests in assessment of NAFLD in different stages of CKD and patients with coronary heart disease (CHD) in comparison with TE findings. Therefore, the aim of the present study was to investigate the usefulness of four liver tests (AST, ALT, GGT and ALP) and four biological scores (HIS, APRI, Forns and FIB-4 scores) in detection of NAFLD in comparison with TE findings in different groups of patients.
Patients and methods The present study, which was conducted as a crosssectional format involved 212 patients; 55 patients with chronic kidney disease (CKD) grade III and IV, 52 patients with End-Stage renal disease (ESRD) who were treated with chronic haemodialysis (HD), 52 renal transplant recipients (RTRs) and 53 patients with coronary heart disease (CHD). Fifty sex- and age-matched individuals without NAFLD and with normal liver and kidney function tests served as controls. None of the involved patients had serological evidence of chronic hepatitis B and/or C virus infection, had a history of alcohol abuse of more than 20 g alcohol per day, had a history of drug treatment causing hepatic steatosis or had a history of gastrointestinal bypass surgery. Other types of metabolic or autoimmune liver disease were ruled out as well. Also, patients with dilated cardiomyopathy diagnosed by echocardiogram with systolic dysfunction of one or both ventricles, ejection fraction lower than 55 %, ventricular dilatation and left ventricular diastolic diameter bigger than 57 mm were excluded from the study. Due to the technical reasons (failed TE), mainly due to body mass index (BMI) > 30 kg/m2, 10 patients were excluded from the analysis. Therefore, 202 patients take a part in further analysis. CKD was defined as estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease; MDRD formula) ≤ 60 ml/min/1.73 m2 for > 3 months. The mean eGFR in CKD group of patients was 32.2 ± 13 ml/ min/1.73 m2. Fifty ESRD patients that were treated with chronic haemodialysis for at least 6 months had eGFR 7.1 kPa. Measurements were performed using the M probe (at the 3.5 MHz) on the right lobe of the liver trough intercostals spaces with the patients lying supine with the right arm placed behind the head to facilitate access to the right upper quadrant of the abdomen. The tip of the probe transducer is placed on the skin between the rib bones at the level of the right lobe of the liver where liver biopsy would be performed. These were done using only the M probe because the CAP algorithm is specific to this device. Ten successful measurements were performed on each patient and only cases with 10 successful measurements were considered as valid and were used for study analysis. Therefore, examinations with no successful measurements after ≥ 10 attempts were deemed failures. The success rate was calculated as the number of successful measurements divided by the total number of measurements. All scans were performed by the same investigator. Therefore, CAP being implemented on TE, both steatosis and fibrosis can be evaluated simultaneously. According to this evaluation, NAFLD was defined by the presence of steatosis with CAP values ≥ 238 dB.m−1 regardless of presence or absence of any stage of fibrosis [11]. The APRI, the Forns index and FIB-4 index were obtained to asses liver fibrosis, and were calculated based on the following formulas: FIB-4 = age [years] × AST/platelet count × ALT APRI = AST/platelet Forns index = 7.811 − 3.131 × ln platelet + 0.781 × ln GGT + 3.647 × ln age − 0.014 × cholesterol
13
For the assessment of liver steatosis, HIS score was obtained according to the following formula: HSI score = 8 × ALT/AST ratio + BMI + 2 (if diabetic) + 2 (if female) We compared the APRI, Forns index and FIB-4, as well as the HIS score with the presence and degree of fibrosis/ steatosis detected by FibroScan®. Patients were informed of the purpose and method of the research and the study was done in accordance with the Declaration of Helsinki. Statistical analysis of data was performed using descriptive statistics (mean and standard deviation). Categorical variables were tested by chi-square test. Testing the importance of the difference of two independent groups was performed using t-test. The Pearson or Spearman correlation coefficient was used to express correlations between variables. Discrimination was tested using the receiver operating characteristic (ROC) curves and by comparing areas under the curve (AUCs). AUCs between 0.7 and 0.8 were classified as “acceptable” and between 0.8 and 0.9 as “excellent” discrimination. P-value 7 kPa. We were interested to explore whether CHD patients with TE defined NAFLD and with normal kidney function had a higher values of four investigated liver test in comparison to other three groups of patients and control subjects. As it was shown in Table 2 CHD-NAFLD patients had statistically higher values of AST and ALT in comparison to other three groups of patients and control subjects. Also, they had statistically significant higher values of GGT in comparison with HD and RTRs groups of patients, as well as in comparison to control subjects. In the next step, we were investigated the usefulness of four liver test (AST, ALT, GGT and ALP) in assessment of NAFLD in comparison with TE findings in four groups of patients. We didn’t find any statistically significant correlation between CAP levels and investigated liver tests in CKD and HD patients as well as in RTRs. On the other hand, we have found that ALT, AST and GGT levels were
Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease
3
original article
Table 1 Demographic characteristics of analyzed patients CKD (n = 52)
HD (n = 50)
RTRs (n = 50)
CHD (n = 50)
Controls (n = 50)
66.0 ± 7.9
68.1 ± 9.6
66.4 ± 10
66.5 ± 6.3
66.1 ± 11.3
Male
27 (51.9 %)
26 (52.0 %)
26 (52.0 %)
26 (52.0 %)
26 (52.0 %)
Female
25 (48.1 %)
24 (48.0 %)
24 (48.0 %)
24 (48.0 %)
24 (48.0 %)
Characteristic Age (y) Sex, n(%)
Etiology Diabetic nephropathy
15 (28.8 %)
13 (26.0 %)
5 (10.0 %)
/
Nondiabetic nephrop
20 (38.5 %)
15 (30.0 %)
10 (20.0 %)
/
Glomerulonephritis
10 (19.2 %)
10 (20.0 %)
15 (30.0 %)
/
Polycystic kidney disease
5 (9.6 %)
5 (10.0 %)
10 (20.0 %)
/
Interstitial nephritis
0 (0 %)
2 (4.0 %)
6 (12.0 %)
/
Other
2 (3.8 %)
5 (10.0 %)
4 (8.0 %)
BMI (kg/m2)
27.2 ± 2.5
24.8 ± 3.2
26.6 ± 1.8
27.4 ± 3.3
/ 25.0 ± 1.2
Hypertension, n(%)
42 (80.8 %)
45 (90.0 %)
48 (96.0 %)
44 (88.0 %)
0
Diabetes, n(%)
30 (57.7 %)
20 (40.0 %)
10 (20.0 %)
25 (50.0 %)
0
Dyslipidemia, n(%)
45 (86.5 %)
42 (84.0 %)
41 (82.0 %)
40 (80.0 %)
0
eGFR (ml/min/1.73 m2)
32.2 ± 13.3
–
46.2 ± 19.0
69.5 ± 6.3
102.7 ± 3.0
Therapy ACE-I/ARBs, n(%)
25 (48.1 %)
22 (44.0 %)
22 (44.0 %)
26 (52.0 %)
0
CCB, n (%)
35 (83.3 %)
38 (76.0 %)
38 (76.0 %)
35 (70.0 %)
0
BB, n (%)
18 (34.6 %)
20 (40.0 %)
21 (42.0 %)
28 (56.0 %)
0
Diuretics, n (%)
12 (23.1 %)
20 (40.0 %)
18 (36.0 %)
20 (40.0 %)
0
Statins, n (%)
40 (76.9 %)
35 (70.0 %)
35 (70.0 %)
40 (80.0 %)
0
Antidiabetic drugs, n(%)
20 (38.5 %)
10 (20.0 %)
5 (10.0 %)
15 (30.0 %)
0
Insulin, n(%)
7 (13.5 %)
7 (14.0 %)
3 (6.0 %)
8 (16.0 %)
0
y years, CKD chronic kidney disease, HD hemodialysis, RTRs renal transplant recipients, CHD coronary heart disease, NAFLD non-alcoholic fatty liver disease, BMI body mass index, NS non-significant
Table 2 Comparasion of four liver test between CHD group and other three groups of patients, as well as between CHD and control subjects CHD (n = 50)
CKD (n = 52)
HD (n = 50)
RTR (n = 50)
Controls (n = 50)
p*
p**
p***
P****
AST (IU/L)
36.2 ± 12.3
20.8 ± 9.0
11.9 ± 3.8
18.4 ± 5.5
21.2 ± 1.1
