Noninvasive Alternatives to Assess Liver Fibrosis: Ready for Prime Time?

William F. Balistreri, MD


December 02, 2014

In This Article

Imaging Techniques

Transient Elastography

Over the past 5 years, transient elastography (TE) has become accepted as a noninvasive marker of fibrosis. TE, which relies on sonic detection of liver stiffness to predict hepatic fibrosis, has been validated in patients with chronic hepatitis.[19] TE methodology offers several distinct advantages: a brief procedure time, immediate availability of results, and the option of performing the procedure in real time at the bedside or in the outpatient clinic.

TE has some limitations. As with any tool, the results are often in the hands of the user. Interpretation must be correlated with the clinical context and other test results (biochemical, radiologic, and endoscopic).[20] In addition, liver stiffness may be overestimated in the presence of confounding factors, such as obesity, extrahepatic cholestasis, and congestive heart failure.[21] Appropriate cut-off values for diagnosing fibrosis and distinguishing cirrhosis must be further defined for each assay.[22] Numerous published studies, some of which are summarized here, have addressed the rationale, reliability, and limitations of this technique.

Wong and colleagues examined the accuracy of TE as measured by FibroScan® (Echosens; Paris, France) among patients with nonalcoholic fatty liver disease (NAFLD).[23]Liver stiffness increased significantly with fibrosis. TE was highly accurate for detecting significant/advanced fibrosis and cirrhosis. Its accuracy was not affected by body mass index (BMI) or steatosis grade and was similar to that of other clinical and biochemical noninvasive measures: APRI, FIB-4, NAFLD fibrosis score, and BARD score (derived from BMI, AST/ALT ratio, and the presence of diabetes).

Degos and colleagues[24] compared the accuracy of TE, assessed using FibroScan, with that of serum biomarkers in the prediction of significant biopsy-proven fibrosis in patients with chronic viral hepatitis. The overall accuracy of FibroScan was significantly higher than that of biomarkers.

Pang and colleagues[17] tested the ability of liver stiffness measurement by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease. They used Cox regression to determine the independent association between liver stiffness and hepatic complications or death. After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications. TE may help estimate prognosis and guide management of patients with chronic liver disease.

Significant fibrosis may be present in patients with NAFLD despite normal liver tests and ultrasonography.[5,25] Liver stiffness measurement by TE proved to be useful and specific to screen for cirrhosis in the general population and to detect undiagnosed chronic liver disease in apparently healthy persons.[26,27] Liver stiffness values in the general population were found to be influenced independently by sex, BMI, and the metabolic syndrome.[28,29]

Liver stiffness values vary after a test meal, presumably owing to adaptation of the hepatic microcirculation to increased portal blood flow; postprandial hyperemia is associated with a greater increase in portal pressure in patients with cirrhosis.[30,31] Arena and colleagues[32] characterized the "confounding" increase in liver stiffness after a standardized meal in patients with chronic HCV infection at different stages of evolution of the process of fibrogenesis. They detected evidence of the confounding effect of a meal on the accuracy of liver stiffness measurements for the prediction of fibrosis stage in patients with chronic HCV hepatitis and suggested that patients should fast for 120 minutes before TE is performed.

Magnetic Resonance Elastography

Several MRI techniques have also been proposed for assessing hepatic fibrosis. The most common approach is magnetic resonance elastography (MRE).[5,33,34,35,36,37] MRE quantitatively measures and visualizes propagating acoustic shear waves that progress through liver tissue.[5,38] This test has been of value in the assessment of chronic liver disease in children, a population in which determination of the stage of liver injury is especially limited by lack of validated noninvasive biomarkers of histologic severity. In a case series of 35 children with chronic liver disease, including severely obese children, Xanthakos and colleagues[38] demonstrated that MRE is feasible and accurate in detecting significant hepatic fibrosis.


Acoustic radiation force impulse (ARFI) imaging is a promising method that involves the mechanical excitation of tissue using short-duration acoustic pulses. The ARFI method can be embedded into a conventional ultrasonographic scanner to allow formal examination of the hepatic parenchyma as well.[7] Several published studies have addressed the rationale, reliability, and limitations of this technique; preliminary results suggest very similar performance to that of TE, although further validation is warranted.

Leung and colleagues[6] documented the utility of shear-wave (SW) elastography for assessing liver fibrosis in patients with chronic hepatitis B and compared its performance with that of TE. SW elastography of the liver, SW elastography of the spleen, and TE of the liver were compared and correlated with biopsy-derived fibrosis scores. SW elastography of the liver showed significantly higher accuracy than TE of the liver and SW elastography of the spleen in all fibrosis stages. SW elastography of the liver had a higher success rate than TE of the liver (98.9% vs 89.6%). Real-time SW elastography was also shown to be accurate for assessing liver fibrosis in patients with chronic hepatitis C.[39]

Spleen stiffness as a predictive model. Takuma and colleagues[40] also documented the prognostic value of spleen stiffness, as detected by ultrasonography (ARFI imaging), in the evaluation of patients with cirrhosis, specifically differentiating patients at low risk for decompensation from those at high risk. Similar results were documented in other centers and in a pediatric population.[41,42]

Not the End of Liver Biopsy Yet

It seems that these noninvasive techniques have had an impact by decreasing the number of liver biopsies performed. In addition, such modalities as MRE have given us a "number" to share with the patient—one that reflects the degree of liver fibrosis.

However, the story is incomplete. More data are needed, including studies that compare strategies using TE, MRE, ARFI, or biomarkers (perhaps in combination) in various populations. Finally, the cost-effectiveness of each screening/monitoring strategy must be further evaluated before broad implementation can be recommended.


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