REVIEW
Fibroscan
Keyur Patel, M.D., and Julius Wilder, M.D., Ph.D.
The management of chronic liver disease has traditionally
relied on liver biopsy to evaluate for fibrosis and cirrhosis.
However, liver biopsy is invasive and associated with a risk
of complications, as well as significant observer and sam-
pling error. In recent years, several noninvasive serum bio-
markers and imaging methods have been developed to
assess for liver fibrosis. Transient elastography (FibroScan;
EchoSens, Paris, France), an ultrasound-based technique
(Fig. 1), was initially developed by the food industry to
assess the maturity of cheese1 and is an accurate and safe
means for assessing the severity of fibrosis in chronic liver
disease.
FibroScan
Liver biopsy has historically been the primary means to
evaluate for fibrosis and monitor disease progression, but it
has significant limitations. Liver biopsy is an invasive proce-
dure that can result in significant complications.2 Accurate
assessment of fibrosis stage is further limited by sampling
error and interobserver variation.3,4 Vibration-controlled
transient elastography (VCTE) utilizing FibroScan uses an
ultrasound transducer probe (Fig. 2) to create an elastic
shear wave through vibrations of mild amplitude and low
frequency (50 Hz), which are transmitted through liver tis-
sue. The probe utilizes pulse-echo ultrasound to follow the
propagation of the shear wave to measure velocity (m/s)
and provide a liver stiffness measurement (LSM) in a repre-
sentative volume of liver tissue that is 100-fold greater than
obtained by needle biopsy (Fig. 3). The LSM is expressed in
kilopascals (kPa) that correlate with fibrosis stage.5,6 Fibro-
Scan assessment is safe and easily performed in 5 to 10
minutes in any clinic or outpatient setting. Patients only
need to fast 2 to 3 hours prior to the procedure because of
the potential increase in liver stiffness from postprandial
blood flow.7 FibroScan cannot be performed in individuals
Abbreviations: AUROC, area under the receiver operator characteristic curve; CHB, chronic hepatitis B; CHC, chronic hepatitis C; F, fibrosis; HBV, hepatitis
B virus; HCC, hepatocellular carcinoma; kPa, kilopascals; LSM, liver stiffness measurement; NAFLD, nonalcoholic fatty liver disease; VCTE, vibration-con-
trolled transient elastography.
From the Duke Clinical Research Institute and Duke University Medical Center, Durham, NC.
Potential conflict of interest: Nothing to report.
View this article online at wileyonlinelibrary.com
C 2014 by the American Association for the Study of Liver Diseases
V
doi: 10.1002/cld.407
97 Clinical Liver Disease, Vol 4, No 5, November 2014
with ascites, and has higher failure rates with standard M
probes in obese and pediatric patients, although XL and S
probes have been developed to improve LSM reliability.8-10
VCTE must be interpreted with caution in other clinical set-
tings such as significant transaminitis,11 sinusoidal conges-
tion,12 extrahepatic cholestasis,13 age,14 and steatosis.15,16
Hepatitis C
The initial studies for VCTE were performed in chronic
hepatitis C (CHC) and showed that VCTE was 99% effective
in detecting cirrhosis and 88% effective in detecting fibro-
sis.5 There have been numerous validation studies in CHC
patients indicating that LSM correlates strongly with the
METAVIR fibrosis stage with area under the receiver opera-
tor characteristic curve (AUROCs) of 0.84, 0.89, and 0.94
for significant fibrosis (F  2), F3 to F4 and F4, respec-
tively.17 Hence, for CHC, VCTE can be used as a means of
detecting severe fibrosis (LSM > 9.6 kPa) and cirrhosis (>
12.5 kPa) (Table 112), and a lower LSM (< 7.1 kPa)
excludes significant fibrosis.18 The combination of VCTE
and serum biomarkers such as FibroSure (LabCorp, Bur-
lington, NC) provide improved diagnostic performance.19,20
With increased availability of direct-acting antiviral therapy,
detection of cirrhosis and prognostic information will
assume a greater clinical relevance than differentiating
between mild and moderate–severe disease. VCTE has been
used to evaluate for portal hypertension and the sequelae of
chronic liver disease. VCTE correlates with the hepatic
venous pressure gradient (HVPG), presence of esophageal
varices, and development of hepatoma.21
Hepatitis B
VCTE has shown promise in chronic hepatitis B (CHB).
Although the LSM thresholds differ from CHC and other
chronic liver disease, these results have to be interpreted in
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 R E V I E W
Figure 1 FibroScan 502 Touch. Adapted from Echosens.
Figure 2 The FibroScan Transducer and Vibrator. Adapted from Echosens.
98 Clinical Liver Disease, Vol 4, No 5, November 2014
Patel and Wilder Fibroscan
the context of the phase of CHB infection. The performance
of VCTE is similar to CHC, with 84% and 65% positive and
negative predictive values, respectively, for a LSM threshold
of 7.0 kPa (Table 1 and 2).22 However, whereas VCTE per-
forms equally well in both CHB and CHC for fibrosis stages
F  3, findings are suboptimal for stages F  2; greater nec-
roinflammatory changes may induce higher LSM values.23
Hence, different LSM threshold values must be considered
based on the natural history phase of CHB infection. There
appears to be a role for VCTE in the evaluation and risk
stratification for hepatocellular carcinoma (HCC) in CHB. A
combined LSM-HCC score, based on VCTE, age, serum albu-
min, and hepatitis B virus (HBV) DNA level, was shown to
have higher predictive AUROCs than the traditionally used
CU-HCC risk score.24 The Chinese University-HCC risk
score is used to predict the risk of HCC in patients with
chronic HBV on antiviral therapy. The score was created by
the Chinese University of Hong Kong and is composed of
age, albumin level, bilirubin level, HBV DNA level, and cir-
rhosis. The score ranges from 0 to 44.5.
Primary Biliary Cirrhosis and Primary
Sclerosing Cholangitis
VCTE has performed well for the diagnosis of severe
fibrosis or cirrhosis in primary biliary cirrhosis. Further-
more, VCTE had better diagnostic performance than bio-
chemical markers for  F2,  F3, or cirrhosis (Table 1 and
2).25 VCTE has been evaluated in primary sclerosing chol-
angitis, and LSM is independently linked to fibrosis stage,
has good diagnostic accuracy for severe fibrosis and cirrho-
sis,26 and once again has improved diagnostic performance
compared to many serologic markers of fibrosis and
cirrhosis.26
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 R E V I E W Patel and Wilder Fibroscan

TABLE 2 Type of Liver Disease and Characteristics of Transient Elastog-

raphy for Identifying Cirrhosis

Cutoff (kPa) Sensitivity Specificity PPV NPV AUROC

HCV 12.5 .84 .94 .58 .98 .93

HBV 1 .75 .90 .39 .98 .94
PBC 16.9 .93 .99 .93 .99 .99
PSC 14.3 1.00 .88 .56 1.00 .95
NAFLD 10.5 .78 .96 .70 .97 .94
HCV1HIV 14.6 .91 .88 .83 .94 .94

Abbreviatons: NPV, negative predictive value; PBC, primary biliary cir-

rhosis; PPV, positive predictive value; PSC, primary sclerosing
cholangitis.

is similar to serum markers for significant fibrosis but

Figure 3 Comparison between successive ultrasound signals to calculate
local strains as a function of time and space. Adapted from Echosens.
appears to have better diagnostic accuracy for identifying
cirrhosis (Table 1 and 2).32,33 The specificity and sensitivity
for VCTE for the diagnosis of cirrhosis (LSM  14 kPa) is
88% and 91%, respectively.34,35

Conclusion
Nonalcoholic Fatty Liver Disease VCTE is an important clinical tool for the assessment of
The diagnostic role of VCTE in nonalcoholic fatty liver disease severity in chronic liver disease, which is now incor-
disease (NAFLD) continues to evolve. Although LSM corre- porated into several professional society guidelines and forms
lates with fibrosis in the setting of NAFLD, this association an integral part of routine clinical hepatology practice in
is less impressive than seen in CHC patients27 (Table 1 many countries. Newer probes and assessment of steatosis
and 2). Predictive LSM values for NAFLD patients with aim to address technological limitations, for example, related
advanced fibrosis and steatosis were lower than expected, to obesity and improving the diagnosis of NASH. Future
although reliability for cirrhosis was better. Furthermore, studies should better define the clinical role of VCTE in
the distinction between bland steatosis and steatohepatitis NAFLD management; provide a longitudinal assessment of
can only be reliably made on liver biopsy. There is a higher disease; determine the optimal interval for repeat LSM; and
failure rate or unreliable LSM results in obese patients.28 better define the diagnostic and prognostic role of VCTE in
Combination with simple serum marker algorithms such as combination with serum markers, HVPG, or other imaging
the NAFLD score improves diagnostic reliability.29 Hence, measures of portal hypertension for chronic liver disease of
whereas VCTE has a role in the assessment of NAFLD, varying etiology. VCTE was approved in the United States in
future studies need to determine optimal thresholds for the April 2013, although availability is still limited, partly due to
newer XL probe, and also to further examine the clinical issues regarding CPT codes and financial reimbursement to
utility of the VCTE continued attenuation parameter, which providers that will continue to be addressed. In summary,
provides information on steatosis grade.30,31 VCTE using FibroScan provides a simple, validated, reliable
noninvasive alternative to liver biopsy in the diagnostic
Coinfection With HIV and HCV assessment of chronic liver disease patients with significant
fibrosis and cirrhosis.
In human immunodeficiency virus (HIV)-hepatitis C virus
(HCV) coinfection, LSM correlates with fibrosis stage—and CORRESPONDENCE
Keyur Patel, M.D., Duke Clinical Research Institute and Duke University Medical
Center, PO Box 17969, Durham, NC 27715. Email: keyur.patel@duke.edu
TABLE 1 Type of Liver Disease and Characteristics of Transient
Elastography for Identifying Significant Fibrosis
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