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Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete?

Cleveland Clinic Journal of Medicine. 2010 August;77(8):519-527 | 10.3949/ccjm.77a.09138
August 1, 2010|Cleveland Clinic Journal of Medicine
Emily Carey, DO;William D. Carey, MD
Author and Disclosure Information

Emily Carey, DO
Digestive Disease Institute, Cleveland Clinic

William D. Carey, MD
Transplant Center and Digestive Disease Institute, Cleveland Clinic; Director, Center for Continuing Education; Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University

Address: Emily Carey, DO, Digestive Disease Institute, A30, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail careye2@ccf.org

ABSTRACTLiver biopsy has been used to diagnose chronic liver disease and to assess the degree of hepatic inflammation and fibrosis. However, it is an invasive test with many possible complications and the potential for sampling error. Noninvasive tests are increasingly precise in identifying the cause of many cases of liver disease and even the amount of liver injury (fibrosis). This review discusses the role of noninvasive tests to diagnose liver disease and to assess hepatic fibrosis and cirrhosis.

KEY POINTS

  • Liver biopsy remains an important tool in the evaluation and management of liver disease.
  • The role of liver biopsy for diagnosis of chronic liver disease has diminished, owing to accurate blood tests and imaging studies.
  • Noninvasive tests for assessing the degree of hepatic fibrosis are showing more promise and may further reduce the need for liver biopsy. Elastography, in particular, shows promise in measuring hepatic fibrosis.
  • Liver biopsy is still needed if laboratory testing and imaging studies are inconclusive.

ELASTOGRAPHY, A PROMISING TEST

Hepatic elastography, a method for estimating liver stiffness, is an exciting recent development in the noninvasive measurement of hepatic fibrosis. Currently, elastography can be accomplished by ultrasound or magnetic resonance.

Ultrasound elastography

The FibroScan device (EchoSens, Paris, France) uses a mild-amplitude, low-frequency (50-Hz) vibration transmitted through the liver.37 It induces an elastic shear wave that is detected by pulse-echo ultrasonography as the wave propagates through the organ.

The velocity of the wave correlates with tissue stiffness: the wave travels faster through denser, fibrotic tissue.38,39

Ultrasound elastography (also called transient elastography) can sample a much larger area than liver biopsy can, providing a better understanding of the entire hepatic parenchyma. 40 Moreover, it can be repeated often without risk. This device is in widespread use in many parts of the world, but it is not yet approved in the United States.

A meta-analysis of 50 studies assessed the overall performance of ultrasound elastography for diagnosing liver fibrosis.41 The areas under the receiver operating characteristic curve were as follows:

  • For significant fibrosis: 0.84 (95% CI 0.82–0.86)
  • For severe fibrosis: 0.89 (95% CI 0.88–0.91)
  • For cirrhosis: 0.94 (95% CI 0.93–0.95).

The type of underlying liver disease influenced the diagnosis of significant fibrosis, which was diagnosed most consistently in patients with hepatitis C. The authors concluded that ultrasound elastography had excellent diagnostic accuracy for diagnosing cirrhosis irrespective of the underlying liver disease, while the diagnosis of significant fibrosis had higher variation, which was dependent on the underlying liver disease.

A meta-analysis of nine studies42 showed ultrasound elastography to have a sensitivity of 87% (95% CI 84%–90%) and a specificity of 91% (95% CI 89%–92%) for the diagnosis of cirrhosis. In seven of the nine studies, it diagnosed stage II to IV fibrosis with 70% sensitivity (95% CI 67%–73%) and 84% specificity (95% CI 80%–88%).

Limitations. Ultrasound elastography is less effective in obese patients, as the adipose tissue attenuates the elastic wave, and it has not been reliable in patients with acute viral hepatitis.43 Male sex, body mass index greater than 30, and metabolic syndrome seem to increase liver stiffness, thus limiting the use of this test.44

Until more data are available, the ultimate value of ultrasound elastography in reducing the number of liver biopsies needed remains unknown. However, this test shows potential as a reliable and noninvasive way to assess the degree of fibrosis in patients with liver disease.

Magnetic resonance elastography

From Talawalkar JA. Elastography for detecting hepatic fibrosis: options and considerations. Gastroenterology 2008; 135:299–302; used with permission from the American Gastroenterological Society.
Figure 2. Magnetic resonance elastography uses a vibrating device to induce shear waves in internal organs, which are detected by a modified magnetic resonance imaging machine. In this color-coded image, areas toward the red end of the spectrum are stiffer and therefore contain more fibrosis than areas toward the violet end of the spectrum.
Magnetic resonance elastography appears more promising than ultrasound elastography (Figure 2).32,37 The technique used is similar to that used in ultrasound elastography in that it uses a vibration device to induce a shear wave in the liver. However, in this case, the wave is detected by a modified magnetic resonance imaging machine, and a color-coded image is generated that depicts the wave velocity, and hence stiffness, throughout the organ.

Studies have shown a magnetic resonance scoring system that distinguishes Child-Pugh grade A cirrhosis from other grades to be 93% sensitive and 82% specific.45

Reprinted from Huwart L, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology 2008; 135:32–40; used with permission from the American Gastroenterological Society.
Figure 3. Median values and interquartile ranges (box plots) of values on magnetic elastography, (top), ultrasound elastography, (middle), and the aspartate:platelet ratio index (APRI) (bottom) for each METAVIR fibrosis stage in 96 patients with chronic liver disease. Crosses represent mean values, and error bars indicate the smallest and the largest values that are within 1.5 box-lengths of the 25th and 75th percentiles. Outliers are represented as individual points. In the bottom graph, one outlier has not been represented in the F4 group to maintain the clarity of the graph.
In a recent direct comparison,46 the separation of values for varying stages of fibrosis was poor with the APRI index, fair with ultrasound elastography, and very good with magnetic resonance elastography (Figure 3). Indeed, in magnetic resonance elastography, a value greater than 4.46 kPa indicates cirrhosis (and a value less than 4.13 indicates no cirrhosis) with a high degree of likelihood, and a value less than 2.84 appears to exclude the likelihood of significant fibrosis. These findings need to be confirmed, and assurance is needed that the test performs accurately across all liver disease states.

Cost may limit the use of magnetic resonance elastography, and some patients may be unable to tolerate the procedure because of claustrophobia. It seems clear, though, that this test currently has the most promise in reducing the need for liver biopsy for grading the severity of hepatic fibrosis.

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