2013

Platelets, May 2013; 24(3): 194–199� 2013 Informa UK Ltd.ISSN 0953-7104 print/ISSN 1369-1635 onlineDOI: 10.3109/09537104.2012.688898

ORIGINAL ARTICLE

Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease

Mehmet Celikbilek1, Sebnem Gursoy1, Kemal Deniz2, Ahmet Karaman1, Gokmen Zararsiz3 & Alper Yurci1

1Department of Gastroenterology and Hepatology, Erciyes University, Medical School, Kayseri, Turkey, 2Department of Pathology,Erciyes University, Medical School, Kayseri, Turkey, and 3Department of Biostatistics and Medical Informatics, Erciyes University,Medical School, Kayseri, Turkey

AbstractNon-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most common cause of chronic liver disease worldwide. It hasbeen shown that NAFLD has a strong association with metabolic syndrome and its component like insulin resistance (IR). Cardiovasculardisease has a relation with NAFLD. Platelet volume is an indicator of platelet function and activation. Mean platelet volume (MPV) has beenreported as a risk factor for atherothrombosis. In our study, we aimed to investigate the relation of MPV with NAFLD and IR in the NAFLDpatients. A total of 54 patients with histologically proven NAFLD and 41 healthy age-matched control subject were enrolled in this study.The NAFLD subjects were divided into two subgroups: 42 patients in the insulin resistant group (median age 39.5, females 22 [52%]) and12 patients in the insulin sensitive group (median age 38, females 5 [41.7%]). MPV were significantly higher in the NAFLD group in univariateanalysis (p< 0.05). In the NAFLD patients, we did not find any relation between steatosis grade, lobular inflammation, hepatocellularballooning, NAFLD activity score and fibrosis with MPV value. Among the insulin resistant and sensitive groups in the NAFLD patients MPVvalues were similar. The results of this study showed that MPV, an indicator of platelet activation, increased in biopsy proven NAFLD patientsbut MPV is not correlated with the increase of IR in NAFLD patients. MPV is not related with inflammation and steatosis degree,hepatocellular ballooning and fibrosis in NAFLD patients.

Keywords: Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, mean platelet volume, insulin resistance

Introduction

Non-alcoholic fatty liver disease (NAFLD) is increasingly

recognized as the most common cause of chronic liver disease

worldwide [1]. The disease is a common clinicopathological

condition characterized by significant lipid deposition in the

hepatocytes of the liver parenchyma in the absence of

alcohol abuse, contributing medications and viral hepatitis.

It comprises a disease spectrum which includes variable

degrees of simple steatosis (fatty liver), non-alcoholic

steatohepatitis (NASH) and cirrhosis [2]. It has been shown

that NAFLD has a strong association with metabolic syndrome

and its components like insulin resistance (IR), obesity,

hypertension and dyslipidaemia. NAFLD is now regarded as

the liver manifestation of metabolic syndrome [3–5].

Platelet volume is an indicator of platelet function and

activation [6]. Platelet activity and aggregation capacity can be

easily determined by measuring mean platelet volume (MPV)

[7]. Large platelets have more granules, aggregate more

rapidly with collagen, produce higher levels of thromboxane

A2 and express more glycoprotein Ib and IIb/IIIa receptors

than smaller ones [8–10]. MPV has been reported as a risk

factor for atherothrombosis [6,11]. Elevated MPV values have

been shown in atherothrombotic diseases like acute myocar-

dial ischemia, acute myocardial infarction, coronary athero-

sclerosis and cerebrovascular events. Increase in MPV has also

been reported in situations that are closely associated with IR

like metabolic syndrome, obesity, diabetes mellitus (DM) and

hypertension [11].

In our study, we aimed to investigate the relation of MPV

with NAFLD, the degree of NAFLD activity score (NAS),

NAS components and IR in biopsy proven NAFLD patients.

To the best of our knowledge, no study has been conducted

on the relationship between MPV and IR in biopsy proven

NAFLD patients.

Methods

Study population

A total of 95 patients enrolled in this study between September

2010 and January 2012 at Erciyes University Gastroenterology

Department. Fifty-four patients with histologically proven

NASH were included. The inclusion criteria were as follows:

1–18 years or older, 2-persistently elevated (for at least 6

months) aminotransferases, 3-ultrasonographic presence of

hyperechogenic liver and 4-liver histology with a diagnosis

of NASH without cirrhosis obtained no more than 6 months

before the study design. The exclusion criteria were as

follows: (1) a history of any level of alcohol consumption;

(2) hypertension (4140 systolic, 490 diastolic or antihyper-

tensive use); (3) any other form of chronic liver disease;

(4) use of any medications thought to cause or affect NAFLD;

(5) abnormal thyroid function tests; (6) plasma fasting glucose

�126 mg/dl or antidiabetic drug use; (7) any medication that

Correspondence: Mehmet Celikbilek, Erciyes Universitesi T|p Fakultesi Hastanesi Gastroenteroloji Bilim Dal|, Talas, Kayseri, Turkey.Tel: þ90 505 6615375. Fax: þ90 352 437 52 73. E-mail: drcelikbilek@yahoo.com

(Received 20 March 2012; revised 21 April 2012; accepted 23 April 2012; published online 30 May 2012)

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can interfere with platelet function (e.g. aspirin); (8) heart

failure; (9) valvular heart disease; (10) chronic obstructive

pulmonary disease; (11) peripheral and cerebral vascular

disease; (12) hematologic disorders; (13) acute or chronic

infection; (14) history of cancer; (15) chronic kidney diseases;

and (16) documented coronary artery disease (CAD).

According to the homeostasis model assessment IR index

(HOMA-IR), the NAFLD subjects were divided into two

subgroups: 42 patients in the insulin resistant group (median

age 39.5, females 22 [52%]), and 12 patients in the insulin

sensitive group (median age 38, females 5 [41.7%]). To reduce

the influence of possible confusing factors, we excluded

diseases known to be associated with increased MPV values

such as hypertension, DM, CAD, and cerebrovascular

diseases.

The control group consisted of 41 healthy age-matched

subjects with normal liver enzymes and abdominal ultrasono-

graphy findings. All subjects underwent a clinical examination

and were questioned about their medical history. Body mass

index (BMI) was calculated as body weight/height2.

This study was performed in accordance with the principles

of the Helsinki Declaration. This study was approved by the

ethical committee of the Medical School of Erciyes University

and informed consent was obtained from all participants.

Biochemical measurements

Blood samples were drawn after an overnight fast from an

antecubital vein; fasting plasma glucose, serum basal insulin

level, high-density lipoprotein cholesterol (HDL), triglycerides

(TG), low-density lipoprotein cholesterol (LDL), creatinine,

alanine aminotransferase (ALT), aspartate aminotransferase

(AST), serum total bilirubin, serum indirect bilirubin, alkaline

phosphatase (AP), and gamma glutamyl transferase (GGT)

were determined by the standard methods.

The estimate of IR by HOMA-IR was calculated with

the formula: fasting serum insulin (mIU/l)� fasting plasma

glucose (mmol/l) /22.5 [12]. The 70th percentile HOMA-IR

value in non-diabetic subjects was 2.245 in the Turkish Adult

Risk Factor Study [13]. IR was defined as42.245 in this study.

MPV was measured in a blood sample collected with

ethylene diamine tetra acetic acid (EDTA) as an anticoagulant.

The samples were used within an hour to prevent EDTA

induced swelling. Dastjerdi et al. [14] reported that MPV

measured within an hour of sampling, using both citrate and

EDTA as an anticoagulant were not significantly different

when compared to each other.

Histopathologic analysis

The liver tissue was stained with hematoxylin–eosin and

Masson’s trichrome stains. The review of the specimens was

carried out by a single experienced liver pathologist. All cases

were scored by using NAS [15]. A 4-point scale for steatosis

[(0) <5%, (1) 5–33%, (2) 433–66%, and (3) 466%], lobular

inflammation [(0) no foci, (1) <2 foci, (2) 2–4 foci, and (3)44

foci] and a 3-point scale for ballooning [(0) none, (1) mild, and

(2) moderate-marked] resulted in a maximal sum score of

eight. A NAS score of five correlated with the diagnosis of

NASH, patients with scores <3 were diagnosed as not having

NASH, and patients with scores of three and four were

diagnosed as having borderline NASH. Fibrosis was scored on

the Masson’s trichrome stain by using the NASH scoring

system [(0): none, (1) perisinusoidal or periportal fibrosis,

(2) perisinusoidal and periportal fibrosis, (3) bridging fibrosis,

and (4) cirrhosis]. Steatosis coded as 0¼mild (steatosis grade

1); or 1¼moderate to severe (steatosis grades 2–3). Lobular

inflammation coded as 0¼ absent-mild (lobular inflammation

0–1); or 1¼moderate–severe (lobular inflammation 2–3).

Fibrosis coded as 0¼ no significant fibrosis (F0–F1); or

1¼ significant fibrosis (F2–F4).

Statistical analysis

The Shapiro–Wilk test was used to check the normality

assumptions and the Levene test for the variance homogeneity

of variables. Results are expressed as frequencies (percen-

tages), mean�SD or median (25th and 75th percentiles).

The differences between groups were tested by independent

two-samples t-test, Mann–Whitney U-test, one-way analysis of

variance and the Kruskal–Wallis test for continuous variables

and �2 analysis for categorical variables. Univariate and

multivariate logistic regression analyses were used to identify

the risk factors of NASH. The odds ratios are given with the

95% confidence intervals. Variables which are statistically

significant in univariate analysis were included in the multi-

variate logistic regression analysis. Backward stepwise selec-

tion was used at a stringency level of p< 0.10 to detect the

independent risk factors on NASH. p< 0.05 probability level

was considered statistically significant. All analyses were

performed with SPSS 15.0 (SPSS Inc., Chicago, IL, USA).

Results

The clinical and laboratory data of the 95 patients with

NAFLD and the controls are presented in Table I. Histological

variables were as follows in NAFLD patients: mild steatosis

28 (51.9%), mild lobular inflammation 15 (27.8%), mild

ballooning 40 (74.1%) and mild fibrosis 31 (57.4%). Twenty-

seven (50%) of the NAFLD patients were classified as

borderline NASH according to the NAS score (Table II).

The IR group number was 42 (77.8%) in the NAFLD patients.

Age, LDL and fasting glucose were similar between the

NAFLD and control groups. BMI, systolic blood pressure

(BP), diastolic BP, LDL, TG, AST, ALT, AP, GGT, insulin,

HOMA-IR, MCV and MPV were significantly higher in the

NAFLD group in univariate analysis (p< 0.05). HDL and

platelet count were significantly lower in the NAFLD group

in univariate analysis (p< 0.05). Distributions of MPV

levels in subjects with and without NAFLD were showed in

Figure 1. Multivariate logistic regression analysis showed that

only ALT was significantly associated with NAFLD. Due to

the significant differences in age and sex between the study

groups assessed in univariate analyses, we also adjusted the

logistic regression models for age and sex variables. Both

crude and adjusted regression results are given in Table III.

Among the insulin resistant and sensitive groups in the

NASH patients, age, gender, LDL, fasting glucose, systolic

BP, diastolic BP, LDL, TG, HDL, AST, ALT, AP, platelet

count, MCV and MPV values were similar. BMI and GGT

values were significantly higher in insulin resistant NAFLD

patients than in insulin sensitive NAFLD patients (p< 0.05).

Mean platelet volume in non-alcoholic steatohepatitis 195

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We did not find any statistically significant association

between histopathologic findings and IR in the NAFLD

group. However, the moderate–severe fibrosis group seemed to

be more insulin resistant than the mild fibrosis group (91.3 vs.

67.7%, p¼ 0.084) (Table IV).

In the NAFLD patients, we did not find any relation

between steatosis grade, lobular inflammation, hepatocellular

ballooning, NAS score and fibrosis with MPV value. Only

hepatocellular ballooning was associated with moderate–

severe steatosis (p< 0.05). Platelet count was inversely

associated with lobular inflammation (p< 0.05). Diastolic

BP, fibrosis and steatosis grade were significantly higher

in moderate-marked hepatocellular ballooning (p< 0.05). A

lower platelet count was observed with increased ballooning

grade (p< 0.05). High age, high-fasting glucose levels, insulin

and GGT levels, high HOMA-IR and hepatocellular balloon-

ing were associated with moderate–severe fibrosis (p< 0.05).

We did not find any feature associated with NAS score.

Discussion

This study showed that (I) MPV, an indicator of platelet

activation and an increased a therothrombotic risk factor, is

higher in biopsy proven NAFLD patients than in the healthy

controls; (II) MPV is not related with inflammation and

steatosis degree, hepatocellular ballooning and fibrosis; and

(III) MPV is not correlated with IR in NAFLD patients.

We know that increased platelet activation and aggre-

gation are associated with cardiovascular complications.

Table I. Clinic characteristics and laboratory data of the patients with NAFLD and controls.

Variable Control group (n¼ 41) NAFLD group (n¼ 54) p

Age (years) 36.73� 12.29 40.91� 10.17 0.073Sex

MaleFemale

11 (26.8)30 (73.2)

27 (50.0)27 (50.0) 0.038

BMI (kg/m2) 24.84 (22.36–29.04) 30.02 (27.51–33.93) <0.001Systolic BP (mmHg) 115.00 (110.00–120.00) 120.00 (110.00–130.00) 0.003Diastolic BP (mmHg) 70.00 (65.00–77.50) 80.00 (70.00–80.00) 0.002LDL cholestrol (mg/dl) 114.96� 33.20 121.78� 31.23 0.308HDL cholestrol (mg/dl) 47.59� 13.79 40.03� 7.26 0.002TG (mg/dl) 96.00 (69.00–125.50) 149.00 (108.80–222.50) <0.001Fasting glucose (mg/dl) 89.29� 10.21 92.70� 13.55 0.181AST (|u/l) 17.00 (14.00–20.50) 50.50 (35.00–68.25) <0.001ALT (|u/l) 16.00 (11.00–19.50) 81.50 (51.50–116.25) <0.001AP (|u/l) 69.00 (52.50–78.50) 76.00 (59.00–91.25) 0.048GGT (|u/l) 18.00 (14.00–27.00) 45.00 (29.00–75.75) <0.001Insulin (mIU/ml) 8.05 (5.06–11.87) 15.58 (11.30–23.27) <0.001HOMA score 1.70 (1.11–2.56) 3.70 (2.34–5.43) <0.001MCV (fl) 84.00 (81.55–86.90) 86.55 (82.43–89.33) 0.046Platelet count (103ml) 280.00 (245.00–346.00) 240.00 (192.75–280.50) <0.001MPV (fl) 9.10� 0.82 9.70� 1.13 0.003

Notes: BMI, body mass index; BP, blood pressure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; AST, aspartateaminotransferase; ALT, alanine aminotransferase; AP, alkaline phosphatase; GGT, gamma glutamyl transferase; HOMA, homeostasismodel assessment; MCV, mean corpuscular volume; MPV, mean platelet volume. Values are expressed as n (%), mean� SD or median(25th and 75th percentiles).

Table II. Histological features of 54 patients with NASH.

Variable NASH, n (%)

NAS score3–4 27 (50%)5–8 27 (50%)

Steatosis grade5–33% (steatosis grade 1) 28 (51.9%)433% (steatosis grade 2–3) 26 (48.1%)

Hepatocellular ballooningMild

(ballooning grade 1) 40 (74.1%)Moderate-marked

(ballooning grade 2) 14 (25.9%)Lobular inflammationMild

(lobular inflammation grade1) 15 (27.8%)Moderate–severe

(lobular inflammation grade 2–3) 39 (72.2%)Stage of fibrosis

0–1 31 (57.4%)2–4 23 (52.6%)

Figure 1. The disribution of MPV in subjects with and withoutNAFLD.

196 M. Celikbilek et al.

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Some markers can be used to evaluate platelet activation like

CD62 (P-selectin), CD63, glycoprotein IIb/IIIa receptors,

platelet factor 4 and �-thromboglobulin. These methods are

costly, time consuming and are not omnipresent. In contrast,

MPV is a cost effective and practical method to evaluate

platelet function and activity [16]. Larger platelets are more

active than smaller ones. Larger platelets also have more

granules, produce more thrombotic factors like thromboxane

A2, aggregate more rapidly with collagen and express more

glycoprotein IIb/IIIa receptors [17–19].

MPV has been found to be higher in patients with metabolic

syndrome, obesity, DM, CAD and hypertension, conditions

Table IV. Clinical characteristics and the laboratory data of the insulin resistant and insulin sensitive patientswith NAFLD.

Insulin sensitive group (n¼ 12) Insulin resistant group (n¼ 42) p

Age (years) 37.58� 11.04 41.86� 9.84 0.202BMI (kg/m2) 26.57 (24.72–29.22) 30.94 (28.28–35.01) 0.003Systolic BP (mmHg) 120.00 (110.00–128.75) 120.00 (110.00–130.00) 0.724Diastolic BP (mmHg) 80.00 (71.25–87.50) 80.00 (70.00–80.00) 0.770LDL-C (mg/dl) 122.33� 39.08 121.62� 29.17 0.945HDL-C (mg/dl) 39.92� 7.06 40.06� 7.39 0.953TG (mg/dl) 126.00 (95.50–207.75) 149.50 (115.00–240.00) 0.201Fasting glucose (mg/dl) 86.92� 9.82 94.36� 14.10 0.094AST (|u/l) 45.00 (30.00–66.00) 50.50 (35.00–68.25) 0.525ALT (|u/l) 65.50 (43.00–107.00) 83.50 (53.00–117.50) 0.240AP (|u/l) 83.00 (57.00–94.25) 75.50 (59.00–87.50) 0.610GGT (|u/l) 31.50 (21.00–44.50) 50.50 (35.25–84.00) 0.038Insulin (mIU/ml) 7.70 (6.71–8.85) 18.75 (13.45–24.93) <0.001HOMA-IR 1.67 (1.36–1.80) 4.37 (3.14–6.10) <0.001MCV (fl) 87.25 (84.15–91.85) 86.30 (81.60–89.30) 0.186Platelet count (103ml) 250.17� 63.05 236.45� 60.19 0.494MPV (fl) 9.10 (8.63–9.75) 9.75 (8.80–10.75) 0.133

HistologyNAS (3–4/�5) 5 (18.5)/7 (25.9) 22 (81.5)/20 (74.1) 0.743Lobular inflammation (1/2–3) 3 (20.0)/9 (23.1) 12 (80.0)/30 (76.9) 0.999Steatosis (1/2–3) 6 (21.4)/6 (23.1) 22 (78.6)/20 (76.9) 0.999Hepatocellular ballooning (1/2) 10 (25.0)/2 (14.3) 30 (75.0)/12 (85.7) 0.710Fibrosis (0–1/2–4) 10 (32.3)/2 (8.7) 21 (67.7)/21 (91.3) 0.084

Notes: BMI, body mass index; BP, blood pressure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; AST, aspartateaminotransferase; ALT, alanine aminotransferase; AP, alkaline phosphatase; GGT, gamma glutamyl transferase; HOMA,homeostasis model assessment; MCV, mean corpuscular volume; and MPV, mean platelet volume. Values are expressed asmean�SD, number of cases (%) or median (25th and 75th percentiles).

Table III. Logistic regression analysis results for steatohepatitis.

Crude Adjusted

Variable OR 95% CI W OR 95% CI W

BMI (kg/m2) 1.22 1.11–1.36 14.78 1.29 1.13–1.47 14.05Systolic BP (mmHg) 1.06 1.02–1.10 8.36 1.06 1.01–1.11 6.78Diastolic BP (mmHg) 1.07 1.02–1.13 8.49 1.08 1.02–1.14 7.58LDL cholestrol (mg/dl) 1.01 0.99–1.02 1.05 1.01 0.99–1.02 0.11HDL cholestrol (mg/dl) 0.93 0.89–0.97 9.39 0.94 0.90–0.99 5.95TG (mg/dl) 1.01 1.01–1.02 11.22 1.01 1.01–1.02 8.02Fasting glucose (mg/dl) 1.02 0.99–1.06 1.79 1.02 0.98–1.06 0.81AST (|u/l) 1.52 1.23–1.89 14.80 1.62 1.20–2.19 10.01ALT (|u/l) 1.36* 1.12–1.64 10.06 1.70* 1.01–2.85 3.96AP (|u/l) 1.01 1.00–1.03 2.47 1.01 1.00–1.03 1.45GGT (|u/l) 1.08 1.04–1.12 15.76 1.08 1.04–1.12 13.75Insulin (mIU/ml) 1.06 1.01–1.11 5.96 1.06 1.01–1.11 4.63HOMA score 1.28 1.05–1.56 5.74 1.25 1.01–1.54 4.29MCV (fl) 1.07 1.00–1.15 3.83 1.05 0.98–1.13 1.80Platelet count (103ml) 0.99 0.98–0.99 12.09 0.99 0.98–0.99 7.80MPV (fl) 1.85 1.18–2.90 7.13 1.75 1.09–2.83 5.26

Notes: Adjusted odds ratios are adjusted for age and sex. W, Wald statistic; BMI, body mass index; BP, blood pressure; LDL,low-density lipoprotein; HDL, high-density lipoprotein; AST, aspartate aminotransferase; ALT, alanine aminotransferase;AP, alkaline phosphatase; GGT, gamma glutamyl transferase; HOMA, homeostasis model assessment; MCV, mean corpuscularvolume; and MPV, mean platelet volume. *Statistically significant after multiple logistic regression analysis.

Mean platelet volume in non-alcoholic steatohepatitis 197

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which are closely associated with IR [11,20]. MPV increase

may contribute to diabetes associated vascular damage like

retinopathy, and microalbuminuria in patients with DM [17].

Several studies have found higher MPV values in ischemic

stroke and have implicated the role of MPV in prognosis and

severity in cerebrovascular disease. Evidence suggest a

correlation between an increase in MPV and the risk of

thrombosis [11,18,19,21]. Increased MPV values have also

been reported in patients with NAFLD [22–24]. In these

studies, authors showed that MPV increases in NAFLD

patients but they did not confirm the diagnosis of NAFLD

with liver biopsy. They did not study MPV and its relation with

NAS components, fibrosis, NAS score and IR in NASH

patients. One study with biopsy confirmed NAFLD subjects

did not find any difference in MPV levels between patients and

controls [25]. In newly published data by Alkhouri et al.

with biopsy proven NAFLD, MPV values were higher for

NASH than for simple steatosis and normal biopsy. Also, the

histologic severity of liver injury and inflammation was

related with higher MPV levels in this data [26]. In our study,

we found higher MPV values in biopsy proven NAFLD

patients compatible with Alkhouri et al. We investigated NAS

components, NAS score, fibrosis degree and their relation

with MPV. Our findings did not confirm any relation between

NAS components, NAS score and fibrosis degree with MPV

which is discordant with the findings of Alkhouri et al. As

mentioned before, MPV is a risk factor, a prognostic indicator

and may play a prominent part in acute myocardial infarction

and cerebrovascular disease pathogenesis [11]. We suggest

that MPV may be considered as an important risk factor in

vascular complications of NAFLD.

In one study an association between MPV and ischemic

electrocardiographic changes was found and MPV tended to be

higher in subjects with higher HOMA index levels in elderly

subjects [27]. In a non-obese and normoglycemic population

with CAD, MPV values were found to be significantly higher

in the insulin resistant group than in the insulin sensitive group

and researchers mentioned the close connection between IR

and MPV [28]. Another study investigated the relationship

between IR and MPV levels in obese adolescent NAFLD

patients and found a positive correlation between MPV and

HOMA-IR [24]. However, the researchers did not study the

relationship between IR and MPV in patients with biopsy

proven NAFLD. For the first time in the literature, we

investigated the direct relationship between IR calculated as

HOMA-IR and MPV in non-diabetic and non-hypertensive

patients with biopsy proven NAFLD. According to our

findings, although MPV was higher in the NAFLD group

than in controls, it was not related with IR in NAFLD patients.

Cytokines are central mediators of hepatic inflammation

and cytokines derived from adipose tissue are thought to play

a key role in NAFLD [29,30]. In one review, the authors

suggested that adipose tissue and a dysfunctioning endothe-

lium may affect bone marrow to produce larger platelets by

cytokines, and added that an altered cytokine profile may

affect platelet size in NAFLD patients [17]. Cytokine plasma

levels are related to hepatic fat content, degree of inflamma-

tion and extent of fibrosis [31]. Basili et al. [32] found

that platelet activation was higher in cirrhotic patients than

in controls and they also reported that cirrhosis is character-

ized by enhanced production of isoprostanes, an index of

oxidative stress in vivo, which is known to elicit platelet

activation. Although we did not examine the cytokine profile

and oxidative stress and their relation with MPV, it makes

sense that MPV may be affected by the altered cytokine profile

and oxidative stress in NAFLD.

There are some limitations in our study. First, the study

population was small and the duration of the study was long

which could affect validity of the results of this study. Second,

the HOMA formula, used to calculate the insulin sensitivity,

is only estimate method and cannot give data as definitive

as the euglycemic–hyperinsulinemic clamp test. As a third

limitation we excluded DM but we did not apply an oral

glucose tolerance test to exclude impaired glucose tolerance.

In conclusion, the results of this study showed that MPV, an

indicator of platelet activation, increased in biopsy proven

NAFLD patients but MPV is not correlated with the increase

of IR in NAFLD patients. In our opinion, cytokine profile,

rather than IR, may play a role in MPV values. Considering

that studies suggest elevated MPV values increase the risk of

CVD, higher MPV values should alert physicians to CVD risk

in NAFLD.

Acknowledgements

We thank Dr Edip Torun, Dr Serkan Dogan, Dr Demet Ozel,

Dr Ahmet Yagbasan for patient support and contributions,

Dr Omer Ozbak|r, Dr Kadri Guven, Dr Mehmet Yucesoy for

their helpful discussion and excellent advise.

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