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a specialised probe of 5MHz ultrasound and low frequency ( 50Hz ) elastic waves . This shear wave measurement provides a quantitative value of stiffness . FibroScan is considered a reliable method for the diagnosis of significant fibrosis ( area under the curve ( AUC ) = 0.84 ), severe fibrosis ( AUC = 0.89 ), and cirrhosis ( AUC = 0.94 ). 11 Limitations of this method are the accuracy of estimation in early fibrosis cases , in obese patients , in those with ascites , and in the presence of congestion and inflammation . 12
Acoustic radiation force impulse ( ARFI ) This method uses conventional ultrasound to measure liver stiffness . ARFI employs short duration acoustic pulses that produce mechanical excitation . The velocity of the resultant waves correlates directly with the extent of liver fibrosis and is expressed as m / s .
It can be performed using routine ultrasound equipment ; the technique can also be used in patients with ascites as it is ultrasound-guided . 13
Studies show that the results of ARFI and FibroScan are comparable in terms of accuracy . 14
Magnetic resonance techniques Conventional and innovative magnetic resonance imaging technologies can be used to measure both liver stiffness and characteristic water-diffusion abnormalities associated with cirrhosis . 15
Magnetic resonance elastography ( MRE ) MRE comprises a three-step process :
• Generation of mechanical waves within the tissues of interest
• Imaging the micron level displacements that are caused by propagating waves using a specialised MRI technique with oscillating motion-sensitising gradients
• Processing the wave images to quantitatively map the physical properties of the liver . 16
The sensitivity and specificity of MRE in predicting liver fibrosis at various stages ( including stage 1 ) are accurate compared with biopsy . In a meta-analysis using biopsy as a standard , MRE was found to be highly accurate for the diagnosis of advanced fibrosis independent of age , sex , BMI , inflammation , and aetiology of the liver disease . 17
Conclusions The area of liver fibrosis and cirrhosis has been extensively studied over the past few decades and , as a result of an increased understanding , several non-invasive tests for fibrosis that are accurate and can replace liver biopsy have
TABLE 3
Summary of some available indirect serological combination panels
Test Markers Reference
European liver fibrosis panel ( ELF )
AST / ALT ratiow
Age , HA , TIMP-1 , PIIINP 3
AST , ALT 4
APRI AST , platelet count 4
FibroTest / FibroSure
Age , sex , bilirubin , GGT , α2M , haptoglobin , apo-A1
FIB-4 index AST , ALT , platelets , age 6
NAFLD fibrosis score
Age , BMI , IFG / DM , platelets , AST / ALT ratio , albumin
Forns index Age , GGT , platelets , prothrombin , cholesterol
Fibrometer Age , AST , platelets , α2M , HA , prothrombin index , urea
BMI , body mass index ; IFG , impaired fasting glucose ; DM , diabetes mellitus ; α2M , alpha 2 macroglobulin ; HA , hyaluronic acid ; TIMP I , tissue inhibitor of metalloproteinase 1 ; Apo A1 , apolipoprotein A1 ; PIIINP , procollagen III N-terminal peptide ; AST , aspartate amino transferase ; ALT , alanine amino transferase ; GGT , gamma glutamyl transpeptidase ; NAFLD , non-alcoholic fatty liver disease
been developed and are being used increasingly in clinical practice .
At present , TE methods ( including ARFI and FibroScan ) have a prominent place in routine clinical use to assess liver fibrosis but serological markers have made a lesser impact . MRE is highly sensitive and specific in detecting fibrosis , but its routine clinical use thus far has been limited due to cost and availability .
The fields of genomics and proteomics are evolving rapidly , and provide opportunities and challenges which , if successful , could transform the diagnosis of fibrosing liver diseases and cirrhosis and improve the assessment and management of these patients greatly . 18
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References 1 Bedossa P . Presentation of a Grid for Computer Analysis for Compilation of Histopathologic Lesions in Chronic Viral Hepatitis C . Cooperative Study of the METAVIR Group . Ann Pathol 1993 ; 13 ( 4 ): 260 – 5 . 2 Grigorescu M : Noninvasive Biochemical Markers of Liver Fibrosis . J Gastrointest Liver Dis 2006 ; 15 ( 2 ): 149 – 59 . 3 Rosenberg WMC et al . Serum markers detect the presence of liver fibrosis : cohort study . Gastroenterology 2004 ; 127:1704 – 13 . 4 Sheth SG et al . AST / ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection . Am J Gastroenterol 1998 ; 93:44 – 8 . 5 Salkic NN et al . FibroTest / Fibrosure
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10 Baranova A et al . Non-invasive markers for hepatic fibrosis . BMC Gastroenterol 2011 ; 11:91 . 11 Friedrich-Rust M et al Performance of transient elastography for the staging of liver fibrosis : a meta-analysis . Gastroenterology 2008 ; 134 ( 4 ): 960 – 74 . 12 Fraquelli M et al . Etiology-related determinants of liver stiffness values in chronic viral hepatitis B or C . J Hepatol 2011 ; 54 ( 4 ): 621 – 8 . 13 Takahashi H et al . Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease : a pilot study . Liver Int 2010 ; 30 ( 4 ): 538 – 45 . 14 Friedrich-Rust M et al . Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis :
a pooled meta-analysis . J Viral Hepat 2012 ; 19 : e212 – e219 15 Taouli B , Ehman RL , Reeder SB . Advanced MRI methods for assessment of chronic liver disease . AJR 2009 ; 193:14 – 27 . 16 Rouviere O et al . MR elastography of the liver : preliminary results . Radiology 2006 ; 240 ( 2 ): 440 – 8 . 17 Singh S et al . Diagnostic performance of magnetic resonance elastography in staging liver fibrosis : a systematic review and meta-analysis of individual participant data . Clin Gastroenterol Hepatol 2015 ; 13:440 – 451 . e6 18 Hannivoort RA et al . Genomics and proteomics in liver fibrosis and cirrhosis . Fibrogenesis Tissue Repair 2012 ; 5:1 .
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