Saudi Journal of Gastroenterology
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Year : 2007  |  Volume : 13  |  Issue : 3  |  Page : 147-149
Fibroscan® : A noninvasive test of liver fibrosis assessment


Gastroenterology Division, Medical Department, King Fahad General Hospital, PO Box 50564, Jeddah 21533, Saudi Arabia

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Date of Submission29-May-2007
Date of Acceptance15-Jun-2007
 

   Abstract 

Determination of the extent of progress of hepatic fibrosis is important in clinical practice, where it may reflect the severity of liver disease and predict response to treatment. Percutaneous liver biopsy is the gold standard for grading and staging of liver disease. However, liver biopsy is an invasive procedure with certain unavoidable risks and complications. Several methods have been studied in an attempt to reach a diagnosis of cirrhosis by noninvasive means. Fibroscan® has been designed to quantify liver fibrosis by means of elastography and found to have reasonably good sensitivity and specificity patterns, especially in patients with advanced fibrosis and can be used as an alternative to liver biopsy.

Keywords: Cirrhosis, FibroScan ® , fibrosis, liver stiffness, plethysmography

How to cite this article:
Al-Ghamdi AS. Fibroscan® : A noninvasive test of liver fibrosis assessment. Saudi J Gastroenterol 2007;13:147-9

How to cite this URL:
Al-Ghamdi AS. Fibroscan® : A noninvasive test of liver fibrosis assessment. Saudi J Gastroenterol [serial online] 2007 [cited 2017 Jul 21];13:147-9. Available from: http://www.saudijgastro.com/text.asp?2007/13/3/147/33470


Hepatic fibrosis develops in almost all patients with chronic liver injury at variable rates, depending in part upon host factors like age, sex and the etiology of liver disease. Evidence shows that the incidence of hepatic fibrosis increases with age and occurs more in males compared to females, especially in patients with chronic hepatitis B and C, genetic hemochromatosis and primary biliary cirrhosis. [1] The composition of the hepatic scar is similar irrespective of the cause of injury. Knowledge of the existence and severity of fibrosis is important from both diagnostic and prognostic viewpoints. Its assessment plays an essential role in the decision-making process and makes it possible to assess the risk of progression to cirrhosis and the onset of its complications. Percutaneous liver biopsy has been in use for more than a century and is the gold standard for grading and staging of liver disease. The American Association for the Study of Liver Diseases, the European Society for the Study of the Liver, the Asian Pacific Association for the Study of the Liver, the National Institutes of Health and other expert panels recommend a pretreatment liver biopsy in most patients who have chronic hepatitis C or chronic hepatitis B. [2],[3],[4],[5],[6] Liver biopsy is an invasive procedure with certain unavoidable risks and complications. Reported rates of death attributed to complications of the procedure range from 1:1000 to 1:10,000. The most common complication is pain and discomfort at the biopsy site and the shoulder, which occur in approximately 20% of the patients. Severe pain requiring intravenous analgesia occurs in up to 7% of the patients. [2] The role of liver biopsy remains a controversial subject however, and several authors have questioned the need for routine liver biopsies in such patients. [7],[8],[9]

Biochemical markers of liver fibrosis may constitute a true alternative to liver biopsies because they can be tested noninvasively, reproducibly and reliably. [10] Several methods have been studied in an attempt to reach a diagnosis of cirrhosis by noninvasive means. Some standard indicators (transaminases, platelets, prothrombin time) have long been recognized as indirect markers of extensive fibrosis. [11],[12]

For several years, scores have been devised with algorithms that combine several indicators determined simultaneously to assess fibrosis in patients with hepatitis C and sometimes in other chronic liver diseases. The Fibrotest is the best validated and most widely used of these. [11]


   Fibroscan® : 0 Technical Considerations Top


FibroScan® (Transient Elastography) is a new and promising sonography-based noninvasive and rapid bedside method for the diagnosis and quantification of hepatic fibrosis (by measuring liver stiffness) in patients with chronic liver disease. It was originally developed to detect solid malignancies in soft tissues such as breast cancer and prostate cancer or to detect thermal lesions resulting from radiofrequency ablation.

FibroScan® has been designed to quantify liver fibrosis by means of elastography, which is based on changes of the physical properties of the liver during chronic liver injury. The apparatus consists of two elements and a control unit: first, an ultrasonic transducer that produces ultrasound waves and operates as a receiver and, second, a piston placed on the transducer sending out a low-frequency vibration. Tissue elasticity is acquired through pulse-echo ultrasound, measuring the speed of the low-frequency elastic shear wave, the S-wave. The faster the wave travels, the more is the loss of elasticity or increase in stiffness. Acquisition time is less than 100 ms and can therefore be used in moving tissues. Sample size is increased by repeated measurements and by increasing measurement depth from 25 to 65 mm, the FibroScan® is more likely to ''hit'' an affected area since fibrosis may be focal. Results of liver elasticity are expressed in kilopascals (kPa). The position of the patient is similar to when performing a liver biopsy, i.e ., on the back, with the right hand under the head. It is possible to measure from different angles in the right as well as the left lobe. The scan can be performed easily; it is inexpensive and produces no side effects. Patients only feel the probe pressure in the intercostal space without anticipated pain. Obesity, ascites and narrow intercostal spaces are physiological boundaries that hamper the accuracy of the test. Sometimes, it may be virtually impossible to take measurements in such patients. [13]


   Fibroscan® : The Evidence Top


Some recent extensive studies, have demonstrated that measurement of liver stiffness with FibroScan® is a good alternative for liver biopsy. The amount of fibrosis can be quantified very easily and reliably and is feasible in more than 95% of the patients. [14],[15],[16] In cirrhotic patients, liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. FibroScan® values ranged from 2.4 to 75.4 kilopascals (median: 7.4 kilopascals). Cut-off values were 7.1 kPa for F ≥ 2, 9.5 kPa for F ≥3 and 12.5 kPa for F = 4 (defined according to the METAVIR classification system). [17]

Areas-under-the-receiver-operating-characteristic curve (AUROCs) (95% confidence interval) were 0.80 (0.75-0.84) for patients with significant fibrosis (F > 2), 0.90 (0.86-0.93) for patients with severe fibrosis (F3) and 0.96 (0.94-0.98) for patients with cirrhosis (F4). Using a cut-off value of 17.6 kPa, patients with cirrhosis were detected with a positive predictive value (PPV) and a negative predictive value (NPV) of 90%. Liver stiffness significantly correlated with clinical, biological and morphological parameters of liver disease. With an NPV > 90%, the cut-off values for the presence of oesophageal varices stage 2/3, cirrhosis Child-Pugh B or C, past history of ascites, hepatocellular carcinoma and esophageal bleeding were 27.5, 37.5, 49.1, 53.7 and 62.7 kPa, respectively. [18],[19],[20]

Erhardt et al. found that the results of transient elastography correlated positively with the histological score of liver fibrosis in 147 patients (r = 0.8; 95% confidence interval (CI): 0.72-0.85; P < 0.001). AUROCs were 0.91 for ≥ F3 fibrosis (95% CI: 0.85-0.96) and 0.94 for cirrhosis (95% CI: 0.90-0.98). Using a cut-off value of 13 kPa for the detection of liver cirrhosis, a sensitivity of 90%, a specificity of 82%, a PPV of 71% and a NPV of 95% were obtained. [21]

Ganne-Carri and his group assessed the accuracy of liver stiffness measurements by FibroScan® for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases due to various causes. After excluding patients with unsuitable biopsy specimens (132 patients) and those with unreliable liver stiffness measurements (118 patients), it was found that the AUROC was 0.95 (95% CI, 0.93-0.96) for the diagnosis of cirrhosis. The cut-off value with optimal diagnosis accuracy was 14.6 kPa (PPV and NPV: 74% and 96%, respectively) with discrepancies among the etiological groups. Eighty patients were misclassified : [1] among 45 of these 80 patients without cirrhosis but with liver stiffness ≥ 14.6 kPa, 27 (60%) had extensive fibrosis and ten (22%) had significant perisinusoidal fibrosis; and two among 35 (5.7%) patients with cirrhosis and liver stiffness ≤ 14.6 kPa, ten (29%) had a macronodular pattern and 25 (71%) had either none or mild activity. They concluded that FibroScan® is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases and is better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False-negatives were mainly attributable to inactive or macronodular cirrhosis. [22]

de Lιdinghen et al. studied 72 patients with human immunodeficiency virus (HIV) / hepatitis C virus (HCV) to assess liver fibrosis by FibroScan.® They compared this assessment with liver biopsy results and found that the liver stiffness values ranged from 3.0 to 46.4 kPa. Liver stiffness was significantly correlated to fibrosis stage (Kendall tau-b = 0.48; P < 0.0001). The AUROC curve of liver stiffness measurement was 0.72 for F ≥ 2 and 0.97 for F = 4. [23]

Ziol and his group compared elastography with findings of histological examinations in 327 patients. They found that liver stiffness measurements and fibrosis grades correlated well, with increasing reliability in more extensive fibrosis (F ≥ 3) or cirrhosis. The lower grades of fibrosis were more difficult to distinguish. With the incorporation of only one patient with fibrosis score F0 in the study population, it was impossible to determine a cut-off value to differentiate between F0 and F1 by FibroScan® . For higher grades of fibrosis, cut-off values could be determined by receiver operating characteristics (ROC) curve analysis. ROC curves were 0.79 for F ≥ 2, 0.91 for F ≥ 3 and 0.97 for F = 4. If the length of the biopsy was increased, the values improved to 0.81, 0.95 and 0.99 for F ≥ 2, F ≥ 3 and F = 4, respectively. The optimal cut-off values were determined at 8.7 and 14.5 kPa for F ≥ 2 and F = 4, respectively. [24]

FibroScan® can be used indirectly to predict the presence of portal hypertension. For example, liver stiffness measurement allows predicting the presence of large esophageal varices in patients with cirrhosis and may help to select patients for endoscopic screening. Values of liver stiffness measurement were 0.84 (95% CI: 0.78-0.90) for the presence of esophageal varices and 0.83 (0.76-0.89) for varices grade ≥ II. Liver stiffness measurement value < 19 kPa was highly predictive of the absence of esophageal varices grade ≥ II (Se: 84%, PPV: 47%, NPV: 93%). [25]


   Conclusion Top


Most studies have demonstrated that measurement of liver stiffness with FibroScan® is a good alternative for liver biopsy. The amount of fibrosis can be quantified very easily and reliably and this technique is feasible in most patients. The liver stiffness measurements and fibrosis grades correlate well with increasing reliability in cases with more extensive fibrosis (F ≥ 3) or cirrhosis. Thus, transient elastography is a promising noninvasive method for assessing advanced fibrosis in patients with chronic liver disease and has a comparable sensitivity and specificity profile to liver biopsy.

 
   References Top

1.Poynard T, Mathurin P, Lai CL, Guyader D, Poupon R, Tainturier MH, et al . Comparison of fibrosis progression in chronic liver disease. J Hepatol 2003;38:257-65.  Back to cited text no. 1    
2.Crockett SD, Kaltenbach T, Keeffe EB. Do we still need a liver biopsy? Are the serum fibrosis tests ready for prime time? Clin Liver Dis 2006;10:513-34.  Back to cited text no. 2    
3.EASL International Consensus Conference on Hepatitis C. Paris, 26-28, February 1999, Consensus Statement. European Association for the Study of the Liver. J Hepatol 1999;30:956-61.  Back to cited text no. 3    
4.Consensus statements on the prevention and management of hepatitis B and hepatitis C in the Asia-Pacific region. Core Working Party for Asia-Pacific Consensus on Hepatitis B and C. J Gastroenterol Hepatol 2000;15:825-41.  Back to cited text no. 4    
5.NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements 2002;19:1-46.  Back to cited text no. 5    
6.Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, et al . A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: An update. Clin Gastroenterol Hepatol 2006;4:936-62.  Back to cited text no. 6    
7.Garcia G, Keeffe EB. Liver biopsy in chronic hepatitis C: Routine or selective. Am J Gastroenterol 2001;96:3053-5.  Back to cited text no. 7    
8.Reiss G, Keeffe EB. Role of liver biopsy in chronic liver disease: Selective vs. routine. Rev Gastroenterol Disord 2005;5.   Back to cited text no. 8    
9.Afdhal NH, Nunes D. Evaluation of liver fibrosis: A concise review. Am J Gastroenterol 2004;99:1160-74.  Back to cited text no. 9    
10.Halfon P, Bourliere M, Pιnaranda G, Cacoub P. Noninvasive methods for predicting liver fibrosis in patients with chronic hepatitis C: Alternatives to liver biopsy. Presse Med 2007;36:457-66.  Back to cited text no. 10    
11.Guιchot J; Groupe de Travail "Marqueurs Biologiques de Fibrose Hιpatique". Noninvasive assessment of liver fibrosis in patients with chronic hepatitis virus C. Presse Med 2006;35:1317-26.  Back to cited text no. 11    
12.De Franchis R, Dell'Era A. Non-invasive diagnosis of cirrhosis and the natural history of its complications . Best Pract Res Clin Gastroenterol 2007;21:3-18.   Back to cited text no. 12    
13.Verveer C, de Knegt RJ. Non-invasive measurement of liver fibrosis: Application of the FibroScan® in hepatology. Scand J Gastroenterol Suppl 2006;243:85-8.  Back to cited text no. 13    
14.Castιra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al . Prospective comparison of transient elastography, Fibrotest, APRI and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343-50.  Back to cited text no. 14    
15.Friedrich-Rust M, Ong MF, Herrmann E, Dries V, Samaras P, Zeuzem S, et al . Real-time elastography for noninvasive assessment of liver fibrosis in chronic viral hepatitis. AJR Am J Roentgenol 2007;188:758-64.  Back to cited text no. 15    
16.Foucher J, Castιra L, Bernard PH, Adhoute X, Laharie D, Bertet J, 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;18:411-2.  Back to cited text no. 16    
17.Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996;24:289-93.  Back to cited text no. 17    
18.Foucher J, Chanteloup E, Vergniol J, Castιra L, Le Bail B, Adhoute X, et al . Diagnosis of cirrhosis by transient elastography (FibroScan® ): A prospective study. Gut 2006;55:403-8.  Back to cited text no. 18    
19.Nguyen-Khac E, Capron D. Noninvasive diagnosis of liver fibrosis by ultrasonic transient elastography (Fibroscan). Eur J Gastroenterol Hepatol 2006;18:1321-5.  Back to cited text no. 19    
20.Nguyen-Khac E. Results and place of Fibroscan in the non-invasive diagnosis of hepatic fibrosis. Rev Med Interne 2007;28:94-102.  Back to cited text no. 20    
21.Erhardt A, L φrke J, Vogt C, Poremba C, Willers R, Sagir A, et al . Transient elastography for diagnosing liver cirrhosis. Dtsch Med Wochenschr 2006;131:2765-9.   Back to cited text no. 21    
22.Ganne-Carriι N, Ziol M, de Ledinghen V, Douvin C, Marcellin P, Castera L, et al . Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 2006;44:1511-7.   Back to cited text no. 22    
23.De Lιdinghen V, Douvin C, Kettaneh A, Ziol M, Roulot D, Marcellin P, et al . Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr 2006;41:175-9.  Back to cited text no. 23    
24.Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, et al . Non-invasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005;41:48-54.   Back to cited text no. 24    
25.Kazemi F, Kettaneh A, N'kontchou G, Pinto E, Ganne-Carrie N, Trinchet JC, et al . Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices. J Hepatol 2006;45:230-5.  Back to cited text no. 25    

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Correspondence Address:
Abdullah S Al-Ghamdi
Gastroenterology Division, Medical Department, King Fahad General Hospital, PO Box 50564, Jeddah 21533
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.33470

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