Liver biopsy (LB) is an important diagnostic tool that assists determination of specific diagnoses and directs therapeutic decisions in patients with acute and chronic liver diseases. Over one hundred years ago, Paul Ehrlich introduced the procedure as a means of studying liver histology.[1
] Since then LB has gained widespread acceptance for the assessment of liver abnormalities associated with many types of liver diseases. The popularity of LB was facilitated by the Menghini “one-second liver biopsy” technique,[2
] which provides samples suitable for various morphological studies, including histochemical, immunohistochemical, ultrastructural and, more recently, molecular biology studies.
The examination of an LB specimen under the microscope is a direct way to identify changes in hepatic tissue and either make a specific diagnosis or determine the grade and stage of chronic liver disease. When it was initially developed, LB primarily served as a diagnostic aid to determine the etiology of liver dysfunction. However, with expansion of knowledge in relation to pathogenesis and natural history of various liver diseases, and the availability of more sensitive and accurate serologic, virologic, genetic and immunologic laboratory tests as well as radiographic techniques, the role of LB in clinical practice has undergone a major change. LB remains a key test to provide a diagnosis, especially in the presence of significant hepatic dysfunction and lack of diagnosis in spite of a comprehensive laboratory evaluation for viral, genetic and autoimmune diseases. In current practice, however, LB is most often performed to assess the degree of necroinflammatory and fibrotic changes, thereby providing essential prognostic information on which to base therapeutic decisions. LB has remained the “gold standard” mainly because of the absence of better alternatives.
However, at long last, substantial progress has been made to break the monopoly that LB has maintained on the evaluation of hepatic tissue. Alternatives to this invasive test have been proposed and are deemed to be as good as biopsy and less damaging to the patient, and include predictive tests for assessment of steatosis, inflammation and fibrosis.[3
] Additionally, it has become apparent that LB, far from being a “gold standard,” is at best an imperfect standard that has attracted criticism over its general application. Increasing evidence challenges the notion of LB as the reference against which all other techniques must be measured.[4
] Its role remains a controversial subject, and an ever-increasing number of authors have questioned the need for its routine application in all patients with liver dysfunction.[11
Simultaneously, evidence has accumulated promoting the use of noninvasive means of assessing liver histology. While investigators initially focused on a combination of laboratory tests such as reversal of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio or AST/platelet ratio index (APRI), more recently there has been a concerted effort to identify novel markers of fibrosis, necroinflammation and steatosis.[14
] A recent systematic review of noninvasive biomarkers by Poynard et al
] identified a total of 2237 references between 1991 and 2008 to novel biomarkers of liver fibrosis, of which 14 have been validated. This clearly represents an escalating interest in the study of noninvasive markers of liver disease.
The initial international guidelines, consensus statements and expert panel opinions on the management of chronic viral hepatitis were unanimous in their recommendation of LB for pretreatment evaluation of the disease.[20
] However, more recently, the European Association for the Study of the Liver guideline statement for the management of chronic hepatitis B (CHB) published in 2009 supports the use of noninvasive markers for disease stratification, providing credibility to their reliability and reproducibility.[27
] Moreover, the use of such tests is rapidly evolving in practice. A recent survey of 546 hepatologists in France revealed that 81% used the noninvasive biomarker FibroTest–ActiTest (Biopredictive, Paris, France) and 32% used transient elastography, resulting in an impressive reduction in the use of LB by 50% for chronic hepatitis C (CHC) patients.[28
In this article we will discuss the shortcomings of LB. In the same vein, we aim to demonstrate the diagnostic accuracy, reliability and usefulness of noninvasive markers of liver disease and make the case for their utilization as suitable alternatives to LB in the evaluation of chronic liver diseases.