Non-invasive evaluation of liver fibrosis using transient elastography

doi:10.1016/j.jhep.2008.02.008

Journal of Hepatology

Volume 48, Issue 5, May 2008, Pages 835-847

https://doi.org/10.1016/j.jhep.2008.02.008 Get rights and content

Transient elastography (TE, FibroScan^®) is a novel non-invasive method that has been proposed for the assessment of hepatic fibrosis in patients with chronic liver diseases, by measuring liver stiffness. TE is a rapid and user-friendly technique that can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. Limitations include failure in around 5% of cases, mainly in obese patients. So far, TE has been mostly validated in chronic hepatitis C, with diagnostic performance equivalent to that of serum markers for the diagnosis of significant fibrosis. Combining TE with serum markers increases diagnostic accuracy and as a result, liver biopsy could be avoided for initial assessment in most patients with chronic hepatitis C. This strategy warrants further evaluation in other aetiological types of chronic liver diseases. TE appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. As TE has excellent patient acceptance it could be useful for monitoring fibrosis progression and regression in the individual case, but more data are awaited for this application. Guidelines are needed for the use of TE in clinical practice.

Introduction

The prognosis and management of chronic liver diseases largely depend on the extent and the progression of liver fibrosis. For instance, in patients with chronic hepatitis C, the leading cause of chronic liver disease worldwide, precise staging of hepatic fibrosis is paramount as fibrosis is the most important predictor of disease outcome and influences the indication for antiviral therapy [1], [2]. Histopathological examination of a liver specimen obtained by percutaneous biopsy has traditionally been considered as the gold standard for evaluating hepatic fibrosis [3]. However, liver biopsy is an invasive and painful procedure, often with poor patient acceptance and also carries a significant, although small risk of life-threatening complications [4], [5]. The accuracy of liver biopsy for assessing fibrosis has also been questioned, due to sampling errors and intra- and inter-observer variability that may lead to over or underestimation of fibrosis stage [6], [7]. Even when an experienced physician performs liver biopsy and an expert pathologist interprets the results, liver biopsy has up to a 20% error rate in disease staging [8]. In addition, it is certainly not the ideal procedure for serially repeated assessment of disease progression.

These findings thus emphasize the need for non-invasive tools that accurately measure the degree of liver fibrosis. Ideally, a non-invasive marker of liver fibrosis should be liver-specific, easy to perform, reliable and inexpensive. In addition, it should be accurate not only for the grading of fibrosis, but also for monitoring disease progression and treatment efficacy. A variety of surrogate markers have been evaluated for their ability to assess liver fibrosis, mostly in patients with chronic hepatitis C [9], [10], [11], [12]. The latest technological advance in this setting is the measurement of liver stiffness by means of transient elastography (TE).

This special article aims at reviewing the data currently available regarding TE performance in assessing stage and progression of liver fibrosis, and compares it to the other non-invasive methods that have become available for this purpose. This review will also discuss the advantages and limits of TE and perspectives for its rational use in clinical practice.

Section snippets

Principle

TE, using FibroScan^® (Echosens, Paris, France), is a novel non-invasive method that has been proposed for assessment of liver fibrosis by measuring liver stiffness [13]. Briefly, an ultrasound transducer probe is mounted on the axis of a vibrator (Fig. 1A). Vibrations of mild amplitude and low frequency (50 Hz) are transmitted by the transducer, inducing an elastic shear wave that propagates through the underlying tissues. Pulse-echo ultrasound acquisition is used to follow the propagation of

Diagnosis of significant fibrosis

The first issue in the evaluation of a novel diagnostic tool for measuring liver fibrosis is its validation against the current clinical gold standard (liver biopsy) to determine sensitivity, specificity, and predictive values [29]. The standard expression of the effectiveness of a test is to look at the area under the receiver operator characteristic curve (AUROC), which plots the sensitivity over 1 – specificity. The perfect test will score 1.0. This has been done for transient elastography

Comparison and combination with serum markers of fibrosis

TE has certain advantages over indices based on laboratory tests, in that it provides a more direct measurement of fibrosis, is not affected by intercurrent health disorders, and is theoretically applicable to all chronic liver diseases. In a study of 183 patients with chronic hepatitis C, we prospectively compared TE with serum fibrosis markers (FibroTest and APRI) and liver biopsy, all performed on the same day [17]. The combination of TE and FibroTest offered the best diagnostic performance,

Screening for complications of cirrhosis

One promising and most attractive application of TE concerns the monitoring of liver fibrosis progression. In cirrhotic patients with chronic hepatitis C, liver stiffness values range from 12.5 to 75 kPa. It is obviously of great interest to understand whether cut-offs of clinical value exist across this wide range of measurements. Preliminary results from our group [19] suggest that liver stiffness values in cirrhotic patients may increase as liver disease becomes more advanced. In this

How to interpret transient elastography in clinical practice and recommendations for a rational use

TE is a very promising non-invasive method for the assessment of hepatic fibrosis in patients with chronic liver diseases with the best diagnostic performances for severe fibrosis and cirrhosis. However, several important questions remain to be solved including: To what extent does hepatic steatosis influence liver stiffness values? Which cut-offs should be used in patients of different liver disease aetiologies? How can TE be used for monitoring disease progression? Is TE sensitive enough to

Future perspectives

Although there is growing evidence that TE will become an important tool in the future practice of hepatology, there is still work to be done to further define its correct place. The focus should now shift from cross-sectional diagnosis to the utilization of TE in longitudinal studies to look at disease progression, regression and clinical outcomes and priority should be given to large scale validation studies. Indeed, longitudinal monitoring of fibrosis in treated and untreated patients may be

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^☆: The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

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Special ArticleNon-invasive evaluation of liver fibrosis using transient elastography☆

Introduction

Section snippets

Principle

Diagnosis of significant fibrosis

Comparison and combination with serum markers of fibrosis

Screening for complications of cirrhosis

How to interpret transient elastography in clinical practice and recommendations for a rational use

Future perspectives

Hepatology

Hepatology

Hepatology

Ultrasound Med Biol

J Hepatol

Gastroenterology

J Hepatol

J Hepatol

J Hepatol

Clin Gastroenterol Hepatol

J Hepatol

J Hepatol

J Hepatol

J Hepatol

J Hepatol

Liver biopsy

N Engl J Med

Pain experienced during percutaneous liver biopsy

Hepatology

Sources of variability in histological scoring of chronic viral hepatitis

Hepatology

Evaluation of liver fibrosis: a concise review

Am J Gastroenterol

Non-invasive measures of liver fibrosis

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Non-invasive diagnosis of liver fibrosis in patients with chronic hepatitis C

MedGenMed

Non-invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

World J Gastroenterol

Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease

Gut

The ratio interquartile range/median value of liver stiffness measurements is a key factor of accuracy of transient elastography (FibroScan) for the diagnosis of liver fibrosis (abstract)

Hepatology

Non-invasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C

Hepatology

Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study

Gut

Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases

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Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases

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Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations

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Acute viral hepatitis increases liver stiffness values measured by transient elastography

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Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage

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Gender and liver: is the liver stiffness weaker in weaker sex?

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Diagnosis of hepatic steatosis and fibrosis by transient elastography in asymptomatic healthy individuals: a prospective study of living related potential liver donors

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Special Article
Non-invasive evaluation of liver fibrosis using transient elastography☆