Assessing liver fibrosis without biopsy in patients with HCV or NAFLD

Cleveland Clinic Journal of Medicine. 2019 March;86(3):179-186 | 10.3949/ccjm.86a.17118
March 1, 2019|Cleveland Clinic Journal of Medicine
Tavankit Singh, MD;Daniela S. Allende, MD;Arthur J. McCullough, MD
Author and Disclosure Information

Tavankit Singh, MD
Department of Gastroenterology and Hepatology, Cleveland Clinic

Daniela S. Allende, MD
Director, Hepatobiliary Pathology, Department of Pathology, Cleveland Clinic; Associate
Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Arthur J. McCullough, MD
Departments of Gastroenterology and Hepatology and Pathobiology and Transplantation Center, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Arthur J. McCullough, MD, Department of Gastroenterology and Hepatology, A30, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; mcculla@ccf.org

Release date: March 1, 2019
Expiration date: February 29, 2020
Estimated time of completion: 1 hour

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ABSTRACT

Staging of liver fibrosis is increasingly done using noninvasive methods, in some cases obviating the need for liver biopsy. Scores based on laboratory values and demographic variables have been developed and validated for assessing fibrosis in patients with hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD), as have several imaging methods that measure shear-wave velocity, a reflection of fibrosis severity.

KEY POINTS

  • Liver biopsy remains the gold standard for determining fibrosis stage but is expensive and entails risk of complications.
  • For patients infected with HCV, fibrosis stage should be determined with transient elastography, a transthoracic ultrasonographic technique that measures shear-wave velocity.
  • For patients with cirrhosis, transient elastography combined with a platelet count can detect developing portal hypertension and determine whether to screen for esophageal varices.
  • For NAFLD, combined elastography and NAFLD fibrosis score—which incorporates patient characteristics and laboratory test results—should be used to determine the need for liver biopsy.

IMAGING TO PREDICT FIBROSIS STAGE

Conventional ultrasonography (with or without vascular imaging) and computed tomography can detect cirrhosis on the basis of certain imaging characteristics,39,40 including the nodular contour of the liver, caudate lobe hypertrophy, ascites, reversal of blood flow in the portal vein, and splenomegaly. However, they cannot detect fibrosis in its early stages.

The 3 methods discussed below provide more accurate fibrosis staging by measuring the velocity of shear waves sent across hepatic tissue. Because shear-wave velocity increases with liver stiffness, the fibrosis stage can be estimated from this information.41

Transient elastography

Transient elastography uses a special ultrasound transducer. It is highly accurate for predicting advanced fibrosis for almost all causes of chronic liver disease, including HCV infection42,43 and NAFLD.44 The cutoff values of wave velocity to estimate fibrosis stage differ by liver disease etiology.

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Transient elastography should not be used to evaluate fibrosis in patients with acute hepatitis, which transiently increases liver stiffness, resulting in a falsely high fibrosis stage diagnosis.45 It is also not a good method for evaluating fibrosis in patients with biliary obstruction or extrahepatic venous congestion. Because liver stiffness can increase after eating,46 the test should be done under fasting conditions.

A significant limitation of transient elastography has been its poor accuracy in patients with obesity.47 This has been largely overcome with the use of a more powerful (XL) probe but is still a limitation for those with morbid obesity.48 Because many patients with NAFLD are obese, this limitation can be significant.

Transient elastography has gained popularity for evaluating fibrosis in patients with chronic liver disease for multiple reasons: it is cost-effective and results are highly reproducible, with low variation in results among different observers and in individual observers.49 Combined with a platelet count, it can also be used to detect the development of clinically significant portal hypertension in patients with cirrhosis, thus determining the need to screen for esophageal varices using endoscopy.50 Screening endoscopy can be avoided in patients whose liver stiffness remains below 20 kPa or whose platelet count is above 150 × 109/L.

Acoustic radiation force imaging

Unlike transient elastography, which requires a separate transducer probe to assess shear- wave velocity, acoustic radiation force imaging uses the same transducer for both this function and imaging. Different image modes are available when testing for liver stiffness, so a region of interest that is optimal for avoiding vascular structures or masses can be selected, increasing accuracy.51

Acoustic radiation force imaging has been tested in different causes of chronic liver disease, including HCV and NAFLD,52 with accuracy similar to that of transient elastography.53 For overweight and obese patients, acoustic radiation force imaging is more accurate than transient elastography using the XL probe.54 However, this method is still new, and we need more data to support using one method over the other.

Magnetic resonance elastography

Magnetic resonance elastography uses a special transducer placed under the rib cage to transmit shear waves concurrently with magnetic resonance imaging. It has been tested in patients with HCV and NAFLD and has been found to have better diagnostic accuracy than transient elastography and acoustic radiation force imaging.55,56 Patients must be fasting for better diagnostic accuracy57 and must hold their breath while elastography is performed. The need for breath-holding and the high cost limit the use of this method for assessing fibrosis.

BOTTOM LINE FOR ASSESSING FIBROSIS

Algorithm to determine fibrosis stage for nonalcoholic fatty livery disease.
Figure 2. Algorithm to determine fibrosis stage for nonalcoholic fatty liver disease.
Although liver biopsy remains the gold standard for accurately determining fibrosis stage, noninvasive methods, especially imaging techniques, are fast evolving. Guidelines recommend using transient elastography to determine fibrosis stage noninvasively in patients with HCV,58 but a similar recommendation cannot be made for NAFLD with available data. For NAFLD, combined elastography and NAFLD fibrosis score are recommended to determine the need for a liver biopsy (Figure 2).59 Currently, we recommend using a combination of the scores discussed above and the imaging tests.