Clinical Pearls & Morning Reports

By Carla Rothaus

Published August 23, 2017


How can noninvasive tests for liver fibrosis be incorporated into clinical practice?

Liver biopsies are traditionally performed to determine the cause and stage of liver disease, as well as to inform treatment decisions and determine prognosis. Much of the interest in noninvasive evaluation of liver disease comes from the risk of complications with liver biopsy and the technical limitations of the procedure. Read the latest Review Article.

Clinical Pearls

Q. What are some of the limitations of liver biopsy?

A. Sampling error is common, and many liver diseases do not affect the liver uniformly. Complicating matters further, both diagnostic accuracy and disease staging depend on specimen size. Small biopsy samples may be nondiagnostic or may not reveal cirrhosis. Additionally, biopsy interpretation is subjective.

Q. What does liver elastography measure?

A. Liver elastography provides more accurate assessments of advanced fibrosis than imaging tests do. There are multiple approaches to the use of this technique: vibration-controlled transient elastography, magnetic resonance elastography, acoustic radiation force–based elastography, and shear wave elastography. In each case, a shear wave is introduced into the liver across the chest wall by means of a probe, and wave propagation is then evaluated by a receiver in the probe, except that with magnetic resonance elastography, the wave is interpreted by the magnetic resonance scanner. The wave’s velocity is then converted into a measurement of liver stiffness, expressed in kilopascals, which correlates with the fibrosis burden. Liver stiffness is a continuous measure that does not stage fibrosis. Cutoffs suggestive of advanced fibrosis have been proposed but vary substantially according to the technique used and the underlying liver disease; cutoffs also differ among studies of the same disease. The use of any cutoff for liver stiffness therefore carries a degree of uncertainty. In general, elastography offers excellent negative likelihood ratios for advanced fibrosis but much poorer positive likelihood ratios.

Morning Report Questions

Q: How can noninvasive tests for liver fibrosis be incorporated into clinical practice?

A: Risk assessment has shifted from fibrosis staging to the dichotomization of fibrosis as advanced or not advanced. The goal is thus to categorize patients as having a low, indeterminate, or high likelihood of advanced fibrosis. Strategies that reserve biopsy for indeterminate results reduce the number of biopsies needed to accurately risk-stratify patients by more than 70%, as compared with biopsy-first approaches. To incorporate noninvasive indexes into practice, the simplest strategy is to begin with a test that has a high negative likelihood ratio in order to rule out high-risk cases. A useful strategy is to order two tests and seek concordant results. To this end, clinicians should order both a serologic test and an imaging or elastographic test during a single clinic visit, so that patients can be assigned to one of three risk strata: concordant low risk, concordant high risk, or discordant or indeterminate results. Approximately 21% of patients will have discordant or indeterminate results. For these patients, the choice is to repeat the tests or perform a liver biopsy, depending on how the results might change management. The results of each test can vary slightly on different days, and when tests are repeated at a follow-up visit, concordance is achieved — precluding the need for a biopsy — in as many as 70% of patients with discordant results.

Q: When is liver biopsy indicated?

A: Liver biopsy continues to play a role in the management of nonalcoholic fatty liver disease. Despite poor interobserver concordance, only a biopsy can differentiate simple steatosis from nonalcoholic steatohepatitis. Biopsy remains important for the diagnosis of some liver diseases — notably, autoimmune hepatitis, small-duct primary sclerosing cholangitis, and antimitochondrial antibody–negative primary biliary cholangitis — and for treatment decisions in some cases of chronic hepatitis B virus infection. Finally, in rare cases, biopsy is necessary to diagnose infiltrative diseases such as amyloidosis, lymphoma, and granulomatous hepatitis.

Browse more Clinical Pearls & Morning Reports »

NEJM Knowledge+