- Email: [email protected]
Shifting ecological filters mediate postfire expansion of seedling aspen (Populus tremuloides) in Yellowstone
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 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.
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.8-10 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
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 112), 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
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
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. 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
An Official Learning Resource of AASLD
R E V I E W
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 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
Figure 1 FibroScan 502 Touch. Adapted from Echosens.
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
Figure 2 The FibroScan Transducer and Vibrator. Adapted from Echosens.
98
Clinical Liver Disease, Vol 4, No 5, November 2014
An Official Learning Resource of AASLD
Patel and Wilder
R E V I E W
Fibroscan
TABLE 2 Type of Liver Disease and Characteristics of Transient Elastog-
raphy for Identifying Cirrhosis
HCV HBV PBC PSC NAFLD HCV1HIV
Cutoff (kPa)
Sensitivity
Specificity
PPV
NPV
AUROC
12.5 1 16.9 14.3 10.5 14.6
.84 .75 .93 1.00 .78 .91
.94 .90 .99 .88 .96 .88
.58 .39 .93 .56 .70 .83
.98 .98 .99 1.00 .97 .94
.93 .94 .99 .95 .94 .94
Abbreviatons: NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis.
Comparison between successive ultrasound signals to calculate local strains as a function of time and space. Adapted from Echosens.
Figure 3
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
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
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. CORRESPONDENCE Keyur Patel, M.D., Duke Clinical Research Institute and Duke University Medical Center, PO Box 17969, Durham, NC 27715. Email: [email protected]
TABLE 1 Type of Liver Disease and Characteristics of Transient
Elastography for Identifying Significant Fibrosis
HCV HBV PBC PSC NAFLD HCV1HIV
References
Cutoff (kPa)
Sensitivity
Specificity
PPV
NPV
AUROC
7.1 7.2 8.8 8.6 7 7.2
.68 .74 .67 .72 .76 .88
.89 .88 1.00 .89 .80 .66
.88 .82 1.00 .85 .75 .75
.70 .82 .75 .78 .78 .88
.86 .86 .91 .84 .80 .83
Abbreviatons: NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis.
99
Clinical Liver Disease, Vol 4, No 5, November 2014
1.
Benedito J, Carcel J, Clemente G, Mulet A. Cheese maturity assessment using ultrasonics. J Dairy Sci 2000;83:248-254.
2.
Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology 2000;32:477-481.
3.
Afdhal NH. Diagnosing fibrosis in hepatitis C: is the pendulum swinging from biopsy to blood tests? Hepatology 2003;37:972-974.
4.
Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002;97:2614-2618.
An Official Learning Resource of AASLD
R E V I E W
Patel and Wilder
Fibroscan
21. Castera L, Pinzani M, Bosch J. Non invasive evaluation of portal hypertension using transient elastography. J Hepatol 2012;56:696-703.
5.
Sandrin L, Fourquet B, Hasquenoph JM, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003;29:1705-1713.
6.
Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol 2008;48:835-847.
22. Marcellin P, dLV, Dhumeaux D, Poupon R, Ziol M, Bedossa P, et al. Non-invasive assessment of liver fibrosis in chronic hepatitis B using FibroScan (abstract). Hepatology 2005;42:715A.
7.
Arena U, Lupsor Platon M, Stasi C, et al. Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution. Hepatology 2013;58:65-72.
23. Verveer C, Zondervan PE, ten Kate FJ, Hansen BE, Janssen HL, de Knegt RJ. Evaluation of transient elastography for fibrosis assessment compared with large biopsies in chronic hepatitis B and C. Liver Int 2012;32:622-628.
8.
Beaugrand M. [Fibroscan: instructions for use]. Gastroenterol Clin Biol 2006; 30:513-514.
9.
Stasi C, Arena U, Vizzutti F, et al. Transient elastography for the assessment of liver fibrosis in patients with chronic viral hepatitis: the missing tool? Dig Liver Dis 2009;41:863-866.
24. Wong GL, Chan HL, Wong CK, et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol 2014;60:339-345.
10. Foucher J, Castera L, Bernard PH, et al. Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations. Eur J Gastroenterol Hepatol 2006;18:411-412. 11. Tapper EB, Cohen EB, Patel K, et al. Levels of alanine aminotransferase confound use of transient elastography to diagnose fibrosis in patients with chronic hepatitis C virus infection. Clin Gastroenterol Hepatol 2012;10:932-937 e931. 12. Lebray P, Varnous S, Charlotte F, Varaut A, Poynard T, Ratziu V. Liver stiffness is an unreliable marker of liver fibrosis in patients with cardiac insufficiency. Hepatology 2008;48:2089. 13. Millonig G, Reimann FM, Friedrich S, et al. Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology 2008;48:17181723.
25. Corpechot C, Carrat F, Poujol-Robert A, et al. Noninvasive elastographybased assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis. Hepatology 2012;56:198-208. 26. Corpechot C, Gaouar F, El Naggar A, et al. Baseline values and changes in liver stiffness, measured by transient elastography, are associated with fibrosis severity and outcomes of patients with primary sclerosing cholangitis. Gastroenterology 2014;146:970-979; quiz e15–16. doi: 10.1053/j.gastro.2013.12.030. Epub 2013. 27. Gaia S, Carenzi S, Barilli AL, et al. Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis. J Hepatol 2011;54:64-71. 28. Castera L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 2010;51:828-835. 29. Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 2013;10:666-675.
14. Kettaneh A, Marcellin P, Douvin C, et al. Features associated with success rate and performance of FibroScan measurements for the diagnosis of cirrhosis in HCV patients: a prospective study of 935 patients. J Hepatol 2007;46:628-634.
30. de Ledinghen V, Vergniol J, Capdepont M, et al. Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations. J Hepatol 2014;60:1026-1031.
15. Fraquelli M, Rigamonti C, Casazza G, et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007;56:968-973.
31. Shen F, Zheng RD, Mi YQ, et al. Controlled attenuation parameter for noninvasive assessment of hepatic steatosis in Chinese patients. World J Gastroenterol 2014;20:4702-4711.
16. Kim KM, Choi WB, Park SH, et al. Diagnosis of hepatic steatosis and fibrosis by transient elastography in asymptomatic healthy individuals: a prospective study of living related potential liver donors. J Gastroenterol 2007;42:382-388.
32. Castera L, Winnock M, Pambrun E, et al. Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these noninvasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC collaboration. HIV Med 2014;15:3039.
17. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008; 134:960-974. 18. Arena U, Vizzutti F, Abraldes JG, et al. Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatitis C. Gut 2008;57:1288-1293.
33. de Ledinghen V, Douvin C, Kettaneh A, et al. Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr 2006;41:175-179.
19. Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343-350.
34. Vergara S, Macias J, Rivero A, et al. The use of transient elastometry for assessing liver fibrosis in patients with HIV and hepatitis C virus coinfection. Clin Infect Dis 2007;45:969-974.
R as a noninvasive diagnos20. Wilder J, Patel, K. The clinical utility of FibroScanV tic test for liver disease. Med Devices (Aukl) 2014;7:107-114.
35. Andersen ES, Christensen PB, Weis N. Transient elastography for liver fibrosis diagnosis. Eur J Intern Med 2009;20:339-342.
100
Clinical Liver Disease, Vol 4, No 5, November 2014
An Official Learning Resource of AASLD
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 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.
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.8-10 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
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 112), 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
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
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. 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
An Official Learning Resource of AASLD
R E V I E W
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 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
Figure 1 FibroScan 502 Touch. Adapted from Echosens.
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
Figure 2 The FibroScan Transducer and Vibrator. Adapted from Echosens.
98
Clinical Liver Disease, Vol 4, No 5, November 2014
An Official Learning Resource of AASLD
Patel and Wilder
R E V I E W
Fibroscan
TABLE 2 Type of Liver Disease and Characteristics of Transient Elastog-
raphy for Identifying Cirrhosis
HCV HBV PBC PSC NAFLD HCV1HIV
Cutoff (kPa)
Sensitivity
Specificity
PPV
NPV
AUROC
12.5 1 16.9 14.3 10.5 14.6
.84 .75 .93 1.00 .78 .91
.94 .90 .99 .88 .96 .88
.58 .39 .93 .56 .70 .83
.98 .98 .99 1.00 .97 .94
.93 .94 .99 .95 .94 .94
Abbreviatons: NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis.
Comparison between successive ultrasound signals to calculate local strains as a function of time and space. Adapted from Echosens.
Figure 3
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
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
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. CORRESPONDENCE Keyur Patel, M.D., Duke Clinical Research Institute and Duke University Medical Center, PO Box 17969, Durham, NC 27715. Email: [email protected]
TABLE 1 Type of Liver Disease and Characteristics of Transient
Elastography for Identifying Significant Fibrosis
HCV HBV PBC PSC NAFLD HCV1HIV
References
Cutoff (kPa)
Sensitivity
Specificity
PPV
NPV
AUROC
7.1 7.2 8.8 8.6 7 7.2
.68 .74 .67 .72 .76 .88
.89 .88 1.00 .89 .80 .66
.88 .82 1.00 .85 .75 .75
.70 .82 .75 .78 .78 .88
.86 .86 .91 .84 .80 .83
Abbreviatons: NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis.
99
Clinical Liver Disease, Vol 4, No 5, November 2014
1.
Benedito J, Carcel J, Clemente G, Mulet A. Cheese maturity assessment using ultrasonics. J Dairy Sci 2000;83:248-254.
2.
Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology 2000;32:477-481.
3.
Afdhal NH. Diagnosing fibrosis in hepatitis C: is the pendulum swinging from biopsy to blood tests? Hepatology 2003;37:972-974.
4.
Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002;97:2614-2618.
An Official Learning Resource of AASLD
R E V I E W
Patel and Wilder
Fibroscan
21. Castera L, Pinzani M, Bosch J. Non invasive evaluation of portal hypertension using transient elastography. J Hepatol 2012;56:696-703.
5.
Sandrin L, Fourquet B, Hasquenoph JM, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003;29:1705-1713.
6.
Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol 2008;48:835-847.
22. Marcellin P, dLV, Dhumeaux D, Poupon R, Ziol M, Bedossa P, et al. Non-invasive assessment of liver fibrosis in chronic hepatitis B using FibroScan (abstract). Hepatology 2005;42:715A.
7.
Arena U, Lupsor Platon M, Stasi C, et al. Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution. Hepatology 2013;58:65-72.
23. Verveer C, Zondervan PE, ten Kate FJ, Hansen BE, Janssen HL, de Knegt RJ. Evaluation of transient elastography for fibrosis assessment compared with large biopsies in chronic hepatitis B and C. Liver Int 2012;32:622-628.
8.
Beaugrand M. [Fibroscan: instructions for use]. Gastroenterol Clin Biol 2006; 30:513-514.
9.
Stasi C, Arena U, Vizzutti F, et al. Transient elastography for the assessment of liver fibrosis in patients with chronic viral hepatitis: the missing tool? Dig Liver Dis 2009;41:863-866.
24. Wong GL, Chan HL, Wong CK, et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol 2014;60:339-345.
10. Foucher J, Castera L, Bernard PH, et al. Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations. Eur J Gastroenterol Hepatol 2006;18:411-412. 11. Tapper EB, Cohen EB, Patel K, et al. Levels of alanine aminotransferase confound use of transient elastography to diagnose fibrosis in patients with chronic hepatitis C virus infection. Clin Gastroenterol Hepatol 2012;10:932-937 e931. 12. Lebray P, Varnous S, Charlotte F, Varaut A, Poynard T, Ratziu V. Liver stiffness is an unreliable marker of liver fibrosis in patients with cardiac insufficiency. Hepatology 2008;48:2089. 13. Millonig G, Reimann FM, Friedrich S, et al. Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology 2008;48:17181723.
25. Corpechot C, Carrat F, Poujol-Robert A, et al. Noninvasive elastographybased assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis. Hepatology 2012;56:198-208. 26. Corpechot C, Gaouar F, El Naggar A, et al. Baseline values and changes in liver stiffness, measured by transient elastography, are associated with fibrosis severity and outcomes of patients with primary sclerosing cholangitis. Gastroenterology 2014;146:970-979; quiz e15–16. doi: 10.1053/j.gastro.2013.12.030. Epub 2013. 27. Gaia S, Carenzi S, Barilli AL, et al. Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis. J Hepatol 2011;54:64-71. 28. Castera L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 2010;51:828-835. 29. Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 2013;10:666-675.
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Clinical Liver Disease, Vol 4, No 5, November 2014
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