Research Article
Relationship between Serum Cytokeratin-18,
Control Attenuation Parameter, NAFLD Fibrosis Score,
and Liver Steatosis in Nonalcoholic Fatty Liver Disease
Sumitro Kosasih,
1
Wong Zhi Qin,
1
Rafiz Abdul Rani,
2
Nazefah Abd Hamid,
3
Ngiu Chai Soon,
1
Shamsul Azhar Shah,
4
Yazmin Yaakob,
5
and Raja Affendi Raja Ali
1
1
Gastroenterology and Hepatology Unit, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia
2
Gastroenterology Unit, Faculty of Medicine, Universiti Teknologi MARA, Shah Alam, Selangor, 40450, Malaysia
3
Department of Medical and Health Science, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, 71800, Malaysia
4
Department of Public Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia
5
Department of Radiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia
Correspondence should be addressed to Raja Afendi Raja Ali; drafendi@ppukm.ukm.edu.my
Received 27 May 2018; Accepted 29 August 2018; Published 27 September 2018
Academic Editor: Heather Francis
Copyright © 2018 Sumitro Kosasih et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Backgrounds. Te aim of this study was to appraise the relationship between serum fragmented cytokeratin-18(CK-18), controlled
attenuation parameter (CAP), and liver steatosis assessed by ultrasound (US) in nonalcoholic fatty liver disease (NAFLD) patients.
Methods. Patients who underwent abdominal US were recruited, followed with measurement of CAP using Fibroscan
5
and serum
fragmented CK-18 using enzyme-linked immunosorbent assay. Te degree of liver steatosis assessed by US was categorized into mild
(S1), moderate (S2), and severe (S3). Results. A total of 109 patients were included in our study. CAP and fragmented CK-18 level were
signifcantly correlated with liver steatosis grade with r
= 0.56 and 0.68, p=0.001, respectively. NAFLD Fibrosis Score was poorly
correlated with liver steatosis grade (r
s
=-0.096, p=0.318). Using fragmented CK-18 level, area under receiver operating characteristic
(AUROC) curves for S≥2 and S≥3 were excellent (0.82 and 0.84, respectively). Using CAP, AUROC curves for detection of S≥2 and
S≥3 were good (0.76, 0.77, respectively). We also proposed cut-of value of CAP to detect S≥2 and S≥3 to be 263 and 319db/m,
respectively, and fragmented CK-18 level to detect S≥2 and S≥3 (194 and 294 U/L, respectively). Conclusions. Both the fragmented
CK-18 level and the CAP, but not NAFLD Fibrosis Score, were well correlated with hepatic steatosis grade as assessed by US.
1. Introduction
Nonalcoholic fatty liver disease (NAFLD) is the liver pan-
demic in this 21
st
century, afecting 20-45% population
around the world [1–5]. NAFLD has been proven to cause
liver fbrosis, liver cirrhosis, and hepatocellular carcinoma
[6–9]. Not only does it have an adverse outcome to the liver
itself but NAFLD also has been associated with increased
rate of metabolic syndrome [10], cardiovascular diseases, and
chronic kidney disease [11, 12]. Although NAFLD is usually
benign, it may be associated with infammation and hep-
atocyte apoptosis resulting in nonalcoholic steatohepatitis
(NASH) of 20–30% of subjects. One-ffh of these NASH
subjects will progress to develop liver cirrhosis [13].
Liver biopsy is still the gold standard to stage liver fbrosis
as it provides a multitude of information on the infammation
activity. However, considering its invasive nature, sampling
variability, and cost, other noninvasive modalities of imaging
and biomarkers have been developed. Te NAFLD fbrosis
score (NFS) developed by Angulo et al. utilizes six variables
(age, body mass index (BMI), diabetes, aspartatetransami-
nase (AST), alaninetransaminase (ALT), and albumin) which
are commonly available in patient’s assessment. It has been
shown to reduce the need for biopsy in most NAFLD patients
[14]. In NASH, liver cell apoptosis and necroinfamma-
tion play a major role. Serum caspase-cleaved fragmented
cytokeratin-18(CK-18) refects the degree of apoptosis and
has been shown as an independent predictor in diagnosis of
Hindawi
International Journal of Hepatology
Volume 2018, Article ID 9252536, 9 pages
https://doi.org/10.1155/2018/9252536