Nonalcoholic fatty liver disease: Updates in noninvasive diagnosis and correlation with cardiovascular disease

Table 1 Definitions of statistics terms and imaging techniques

Terms	Definition
Area under receiver operating characteristic curve (AUROC)	The AUROC is a measure of how well a parameter can distinguish between two diagnostic groups (diseased/normal)
Accuracy	Consists of Trueness (proximity of measurement results to the true value) and Precision (repeatability or reproducibility of the measurement)
Negative predictive value	Proportion of people with a negative test who are free of the target disorder
Positive predictive value	Proportion of people with a positive test who have the target disorder
Sensitivity	Proportion of people with the target disorder who have a positive test result
Specificity	Proportion of people without the target disorder who have a negative test
Imaging techniques
Ultrasonography-based transient elastography (FibroScan)	Technique whereby shear waves, at a low frequency of 50 Hz, are created by a vibrating probe and transducer applied to the skin overlying the liver
Acoustic radiation force impulse	Use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam
Magnetic resonance imaging-based Proton magnetic resonance spectroscopy	Quantifies hepatosteatosis by measuring proton signals from the acyl groups of hepatocyte triglyceride stores
Magnetic resonance elastography	Obtained by depicting the propagated shear waves, and images of the shear waves are analyzed and used to generate the elastogram

Table 2 Accuracy of noninvasive diagnosis methods for nonalcoholic steatohepatitis

	Cutoff value	AUROC	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Ref.
Biomarkers
Morbidly obese and AST, ALT	2 times of ULN	-	-	-	21	91	[22]
big-γ GT	2.6 U/L	0.85	74	81	83.7	71.2	[27]
CK-18 M30 antigen	121.6 IU/L	0.787	60	97.4	96.4	67.3	[48]
CK-18 M65 antigen	243.82 IU/L	0.809	68.9	81.6	81.6	68.9	[48]
PIIINP	6.6 ng/mL	-	80	68	60	85	[51]
Predictive Models
APRI	0.98	0.85	75	86	34	93	[55]
FIB-4	1.30	0.86	85	65	36	95	[59]
Image assessment
Transient elastography (TE; FibroScan )	6.7 kPa	0.87	77.5	86.7	94.8	54.9	[66]
ARFI	1.2 m/s	0.84	76.9	86.7	95.7	54.1	[66]
Combine TE and ARFI	TE > 6.7 kPa ARFI > 1.2 m/s	-	60.5	93.3	96.8	41.4	[66]
MRE	2.74 kPa	0.93	94	73	85	89	[71]

ULN: Upper limit of normal; PIIINP: Terminal peptide of procollagen III; APRI: AST-to-platelet ratio index; AFRI: Acoustic radiation force impulse; MRE: Magnetic resonance elastography; AUROC: Area under receiver operating characteristic curve; PPV: Positive predictive value; NPV: Negative predictive value.

Table 3 Analysis of laboratory biomarkers associated with nonalcoholic steatohepatitis

Biomarkers		OR	95%CI	P value	Ref.
Ferritin	1.5 times of ULN	1.66	1.05-2.62	0.028	[37]
Adiponectin	per μg/mL increased	0.78	0.64-0.96	0.020	[41]
TNF-α	per μg/mL increased	2.50	1.1-5.7	0.030	[41]
IL-6	> 4.81 pg/mL	33.702	1.699-680.668	0.022	[43]
HOMA-IR	> 2.04	2.33	1.00-5.42	0.050	[53]

ULN: Upper limit of normal; TNF-α: Tumor necrosis factor-α; IL-6: Interleukin-6; HOMA-IR: Homeostasis model assessment of insulin resistance.