Hepatology Liver Fibrosis
Non-invasive Markers of Liver Fibrosis Guillermo Fernández-Varo1
and Wladimiro Jiménez1,2
1. Biochemistry and Molecular Genetics Service; 2. Department of Physiology I, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona
Abstract
Liver biopsy is classically considered the gold standard to assess the extent of fibrosis, although it is associated with the risk of complications and limitations due to observer variability and sampling errors. Thus, several routine laboratory tests combining scores and indexes have been developed and validated as useful non-invasive and inexpensive tools to accurately detect significant fibrosis or cirrhosis in clinical practice. Recently, transient elastography has become a useful, novel, rapid and reproducible method to assess liver fibrosis through the measurement of liver stiffness. Serum markers reflecting the changes in extracellular matrix (ECM) have been investigated individually or in combination for the detection of the severity and progression of hepatic fibrosis and the follow-up of changes related to antiviral treatment. The combination of two non-invasive markers such as imaging methods and scores of biochemical serum markers appears to be a promising strategy, increasing diagnostic performance. This article reviews the most referred non-invasive markers and the perspectives for their use in clinical practice.
Keywords Liver fibrosis, cirrhosis, non-invasive markers, imaging methods, biochemical serum markers
Disclosure: This work was supported by grants from Dirección General de Investigación Científica y Técnica (SAF09-08839 to Wladimiro Jiménez) and from Agència de Gestió d’Ajuts Universitaris i de Recerca (SGR 2009/1496). The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) is funded by the Instituto de Salud Carlos III. The authors thank Siemens Healthcare Diagnostics (Tarrytown, NY) for generously supplying the reagents to measure the fibrosis markers. The authors have no other conflicts of interest to declare. Received: 14 January 2011 Accepted: 19 April 2011 Citation: European Gastroenterology & Hepatology Review, 2011;7(2):93–6 Correspondence: Wladimiro Jiménez, Servicio de Bioquímica y Genética Molecular, Hospital Clinic, Villarroel 170, Barcelona 08036, Spain. E:
wjimenez@clinic.ub.es
Assessment of Liver Fibrosis
Knowledge of the extent of liver fibrosis is essential to determine the progression of liver disease, to establish a prognosis and to make treatment decisions. Currently, liver biopsy is the gold standard for the detection of liver fibrosis. Histological examination of liver biopsy allows classification into different stages depending on the degree of fibrosis. However, it is an invasive method that involves risks and is subject to sampling error due to the small size of the biopsy and the heterogeneous distribution of fibrosis in the liver. It has been reported that in 33% of cases there was a difference of at least one phase histological comparison of two lobes in patients with chronic viral hepatitis C (HCV).1–5
In addition, results vary depending on the
observer and this procedure does not allow dynamic assessment of the progression of fibrosis.5,6
These limitations and the growing need for methods to accurately predict the initial phase of the disease and the progression of fibrosis over time have increased interest in developing non-invasive alternative methods to determine the stages of liver fibrosis. These new procedures are divided into two categories: imaging techniques and tests based on the determination of serum biomarkers.
Imaging Methods
Liver stiffness with transient elastography (TE) measurement (Fibroscan®) is a reliable technique and is used in many centres for the evaluation of liver fibrosis. This imaging method is based on
© TOUCH BRIEFINGS 2011
measuring the stiffness of the liver tissue using ultrasound. Several studies have recently been published showing good results in the detection of liver fibrosis.7–10
The hepatic vein pressure gradient
(HVPG) is an invasive method measuring portal pressure in a reproducible and accurate manner that offers a similar performance in identifying patients with significant fibrosis to that provided by liver biopsy.11
in patients with chronic HCV12 after liver transplantation.13,14
A good correlation has been reported between TE and HVPG and in patients with HCV recurrence Good results have also been obtained by
combining TE and the determination of serum marker levels.15 However, liver stiffness measurements can be difficult in obese patients or those with a narrow intercostal space and may be impossible in patients with ascites.16–17
The diagnostic accuracy and
clinical usefulness of TE and several surrogate biochemical serum markers in predicting significant histological liver fibrosis and cirrhosis in patients with HCV have recently been evaluated in a multicentre prospective study.18
tests, especially TE, may be useful in the prediction of cirrhosis. However, the diagnostic accuracy of non-invasive tests has been shown to be poor for significant fibrosis.
Recently, a new imaging technique has been developed, namely acoustic radiation force impulse (ARFI) (Virtual Touch®, Siemens). This is an upgraded ultrasound device that measures the speed of propagation of short waves generated by the ultrasound transducer in a region of interest of hepatic tissue. In our hospital we prospectively
93
This study has established that non-invasive
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