Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice

Table 1 Imaging modalities for diagnosing nonalcoholic fatty liver disease

Test	Description	Accuracy	Advantages	Disadvantages	Guideline recommendation
Ultrasound	Hyperechoic texture or a bright liver	AUROC 0.93, Sn 85%, Sp 94% for diagnosis of steatosis[33]	Cheap; No radiation; Available; Easy to perform	Low sensitivity in individuals with steatosis < 20% or BMI > 40 kg/m2; Observer-dependency; Influenced by fibrosis or iron overload	The first-line diagnostic test for diagnosing moderate and severe steatosis[32]
Computed tomography	Measurement of liver steatosis with attenuation values of liver and spleen	AUROC 0.99, Sn 100%, Sp 82% for diagnosis of steatosis > 30%[29]	Visualize the whole liver; Higher applicability; Quantify moderate-severe steatosis	Low sensitivity for light-moderate steatosis; Radiation exposure	NA
CAP	Measurement of liver steatosis with ultrasound attenuation by Fibroscan	AUROC 0.82, Sn 69%, Sp 82% for diagnosis of any steatosis[44]	Immediate assessment; Can be used in ambulatory clinic setting; Measure LSM simultaneously	Operator-dependency; Limited sensitivity; High failure rates in obesity patient; Low accuracy for quantifying steatosis; Uncertain cut-off values	The role of CAP for steatosis assessment is inclusive, more future studies are needed to define the role of CAP[32]
Magnetic resonance based techniques	Quantitative measurement of steatosis over the entire liver by adding parameter to MRI scanners	MRI-PDFF: AUROC 0.99, Sn 96%, Sp 100% for diagnosis of any steatosis[49] MRS: Sn 80%, Sp 80% for diagnosing steatosis ≥ 5%[58]	Not affected by obesity; Quantify assess steatosis over the entire liver; Lower sampling variability	Expensive; Time consuming; Device- and operator-dependency; Not suitable for patients with implantable devices	It is excellent to quantify steatosis, but the high price limits its application[32]

AUROC: Area under the receiver operating characteristic curve; Sn: Sensitivity; Sp: Specificity; BMI: Body mass index; CAP: Controlled attenuation parameter; NA: Not applicable; MRI: Magnetic resonance imaging; MRI-PDFF: Magnetic resonance imaging-derived proton density fat fraction; MRS: Magnetic resonance spectroscopy; LSM: Liver stiffness measurement.

Table 2 Biomarker panels for diagnosing nonalcoholic fatty liver disease related fibrosis

Test	Description	Accuracy	Advantages	Disadvantages	Guideline recommendation
APRI	AST/platelet ratio index	AUROC 0.70 for SF, 0.75 for AF, and 0.75 for cirrhosis[28]	High feasibility; Cheap; Reproducible	Low specificity to diagnose AF; The application of two cut-offs could not discriminate between intermediate stages of fibrosis	NA
Fibrosis-4 index	Age, AST, ALT, and platelet count	AUROC 0.75 for SF, 0.80 for AF, and 0.85 for cirrhosis[28]	High feasibility; Cheap; Reproducible	The application of two cut-offs could not discriminate between intermediate stages of fibrosis; Influenced by age	FIB-4 can be used to identify those at low or high risk for AF or cirrhosis [32,34]
NFS	Age, BMI, impaired fasting glucose and/or diabetes, AST, ALT, platelet, Count, and albumin	AUROC 0.72 for SF, 0.73 for AF, and 0.83 for cirrhosis [28]	High feasibility; Cheap; Reproducible	The application of two cut-offs could not discriminate between intermediate stages of fibrosis; Influenced by age; Influenced by interpretation of BMI across different ethnic groups	NFS can be used to identify those at low or high risk for AF or cirrhosis[32]
BARD score	AST, ALT, BMI, and diabetes	AUROC 0.64 for SF, 0.73 for AF, and 0.70 for cirrhosis[28]	High feasibility; Cheap; Reproducible; No intermediate stages of fibrosis	Low specificity to diagnose SF and cirrhosis; Influenced by interpretation of BMI across different ethnic groups	NA

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; AUROC: Area under the receiver-operating characteristics curve; NFS: Nonalcoholic fatty liver disease fibrosis score; APRI: AST/platelet ratio index; NA: Not applicable; SF: Significant fibrosis; AF: Advanced fibrosis.

Table 3 Imaging modalities for diagnosing nonalcoholic fatty liver disease related fibrosis

Test	Description	Accuracy	Advantages	Disadvantages	Guideline recommendation
VCTE	Measuring the velocity of a 50 mHz shear wave, which is positively related to liver stiffness	AUROC 0.83, 0.87, and 0.92 , respectively, for AF, SF, and cirrhosis with M probe[28]; AUROC 0.82, 0.86, and 0.94, respectively, for AF, SF, and cirrhosis with XL probe[117]	Relatively low cost; Good reproducibility Short processing time; Can be used in ambulatory clinic setting	Fasting for 2 h; Device- and operator- dependency; Influenced by obesity, congestion, and inflammation; Uncertain cut-off values; Intermediate stages due to two cut-offs	FibroScan can be used to identify those at low or high risk for AF[32,34]
SWE	A method integrated into conventional ultrasound provides a 2-D, real-time, color map of liver elasticity	AUROC 0.86, 0.89, and 0.88, respectively, for AF, SF, and cirrhosis[123]	Good reproducibility; Not affected by obesity or ascites	Relatively high cost; Fasting for 2 h; Device- and operator- dependency; Quality criteria not well defined	NA
ARFI	A method integrated into a conventional ultrasound measures shear wave speed	AUROC 0.77, 0.84, and 0.84, respectively, for AF, SF, and cirrhosis[123]	Good reproducibility; Not affected by obesity or ascites ROI smaller than transient elastography	High cost; Fasting for 2 h; Device- and operator- dependency; Quality criteria not well defined; Intermediate stages due to two cut-offs	NA
MRE	A noninvasive MRI based method measures liver stiffness by a modified phase-contrast method	AUROC 0.87, 0.90, and 0.91, respectively, for AF, SF, and cirrhosis[131]	Good reproducibility; Not affected by obesity or ascites	High cost; Time consuming; Fasting for 2 h; Device- and operator- dependency; Intermediate stages due to two cut-offs	MRE is clinically useful tools for identifying advanced fibrosis in patients with nonalcoholic fatty liver disease[34]

AUROC: Area under the receiver operating characteristic curve; MRE: Magnetic resonance elastography; VCTE: Vibration-controlled transient elastography; SWE: Shear wave elastography; TE: Transient elastography; ARFI: Acoustic radiation force impulse; NA: Not applicable; ROI: Region of interest.