Fibroscan

Watch a video presentation of this article

Watch the interview with the author

Answer questions and earn CME

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‐controlled transient elastography.

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 sampling error. In recent years, several noninvasive serum biomarkers 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.

Figure 1.

FibroScan 502 Touch. Adapted from Echosens.

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 procedure 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 tissue. 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 representative 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 FibroScan 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 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, 9, 10 VCTE must be interpreted with caution in other clinical settings such as significant transaminitis,11 sinusoidal congestion,12 extrahepatic cholestasis,13 age,14 and steatosis.15, 16

Figure 2.

The FibroScan Transducer and Vibrator. Adapted from Echosens.

Figure 3.

Comparison between successive ultrasound signals to calculate local strains as a function of time and space. Adapted from Echosens.

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 fibrosis.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 operator characteristic curve (AUROCs) of 0.84, 0.89, and 0.94 for significant fibrosis (F ≥ 2), F3 to F4 and F4, respectively.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 1+2), and a lower LSM (< 7.1 kPa) excludes significant fibrosis.18 The combination of VCTE and serum biomarkers such as FibroSure (LabCorp, Burlington, 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

Table 1.

Type of Liver Disease and Characteristics of Transient Elastography for Identifying Significant Fibrosis

	Cutoff (kPa)	Sensitivity	Specificity	PPV	NPV	AUROC
HCV	≥7.1	.68	.89	.88	.70	.86
HBV	≥7.2	.74	.88	.82	.82	.86
PBC	8.8	.67	1.00	1.00	.75	.91
PSC	8.6	.72	.89	.85	.78	.84
NAFLD	7	.76	.80	.75	.78	.80
HCV+HIV	7.2	.88	.66	.75	.88	.83

Abbreviatons: NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis.

Table 2.

Type of Liver Disease and Characteristics of Transient Elastography 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
HCV+HIV	14.6	.91	.88	.83	.94	.94

Abbreviatons: NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis.

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 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 performs equally well in both CHB and CHC for fibrosis stages F ≥ 3, findings are suboptimal for stages F ≤ 2; greater necroinflammatory 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 albumin, 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 cirrhosis. 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. Furthermore, VCTE had better diagnostic performance than biochemical markers for ≥ F2, ≥ F3, or cirrhosis (Table 1 and 2).25 VCTE has been evaluated in primary sclerosing cholangitis, and LSM is independently linked to fibrosis stage, has good diagnostic accuracy for severe fibrosis and cirrhosis,26 and once again has improved diagnostic performance compared to many serologic markers of fibrosis and cirrhosis.26

Nonalcoholic Fatty Liver Disease

The diagnostic role of VCTE in nonalcoholic fatty liver disease (NAFLD) continues to evolve. Although LSM correlates with fibrosis in the setting of NAFLD, this association is less impressive than seen in CHC patients27 (Table 1 and 2). Predictive LSM values for NAFLD patients with advanced fibrosis and steatosis were lower than expected, although reliability for cirrhosis was better. Furthermore, the distinction between bland steatosis and steatohepatitis can only be reliably made on liver biopsy. There is a higher failure rate or unreliable LSM results in obese patients.28 Combination with simple serum marker algorithms such as the NAFLD score improves diagnostic reliability.29 Hence, whereas VCTE has a role in the assessment of NAFLD, future studies need to determine optimal thresholds for the newer XL probe, and also to further examine the clinical utility of the VCTE continued attenuation parameter, which provides information on steatosis grade.30, 31

Coinfection With HIV and HCV

In human immunodeficiency virus (HIV)‐hepatitis C virus (HCV) coinfection, LSM correlates with fibrosis stage—and is similar to serum markers for significant fibrosis but 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

VCTE is an important clinical tool for the assessment of disease severity in chronic liver disease, which is now incorporated into several professional society guidelines and forms an integral part of routine clinical hepatology practice in many countries. Newer probes and assessment of steatosis aim to address technological limitations, for example, related to obesity and improving the diagnosis of NASH. Future studies should better define the clinical role of VCTE in NAFLD management; provide a longitudinal assessment of disease; determine the optimal interval for repeat LSM; and better define the diagnostic and prognostic role of VCTE in combination with serum markers, HVPG, or other imaging measures of portal hypertension for chronic liver disease of varying etiology. VCTE was approved in the United States in April 2013, although availability is still limited, partly due to issues regarding CPT codes and financial reimbursement to providers that will continue to be addressed. In summary, VCTE using FibroScan provides a simple, validated, reliable noninvasive alternative to liver biopsy in the diagnostic assessment of chronic liver disease patients with significant fibrosis and cirrhosis.