The Utility of Liver Biopsy in the Evaluation of Liver Disease and Abnormal Liver Function Tests

Ali Khalifa, MD; David N. Lewin, MD; Roula Sasso, MD; Don C. Rockey, MD


Am J Clin Pathol. 2021;156(2):259-267. 

In This Article

Abstract and Introduction


Objectives: We aimed to assess the value of liver biopsy in the evaluation of abnormal liver tests.

Methods: We analyzed consecutive liver biopsy specimens performed for evaluation of unexplained abnormal liver tests from 2014 to 2018. Diagnoses were categorized histologically and clinically. We determined whether histologic examination led to a specific diagnosis and whether prebiopsy laboratory variables predicted the underlying etiology.

Results: Among the 383 liver biopsy specimens included, chronic hepatitis was the most common histologic (25%) and clinical (17%) diagnosis. Liver biopsy led to a clinical diagnosis in 87% of patients. The most likely clinical diagnoses were autoimmune hepatitis, nonalcoholic fatty liver disease, and drug-induced liver injury (38, 33, and 32 patients, respectively). Using sensitivity, specificity, and positive and negative predictive values, we found that liver tests were not predictive of a specific diagnosis. In patients with no history of liver disease or clinical features of portal hypertension, biopsy specimens revealed histologic cirrhosis in 5% of patients.

Conclusions: Histopathologic diagnoses were made in 85% of patients undergoing liver biopsy for investigation of unexplained liver tests, leading to a clinical diagnosis in 87% of patients. However, neither liver tests themselves nor their patterns were useful in predicting histologic or clinical diagnoses.


Elevated liver function tests (LFTs) are common, being identified in 15% of the general population,[1] and are even more common in patients seen in general internal medicine clinics.[2] For many years, there has been extensive interest in finding reliable noninvasive methods to diagnose liver disease, largely using serologic or immunologic tests. Nevertheless, elevated LFTs that cannot be explained by history, clinical findings, or serologic or immunologic tests remain a difficult clinical challenge, and performing liver biopsy to assess histology remains a cornerstone of diagnosis.

Current data suggest that abnormal liver tests in most of the general population (69%) cannot be explained by obvious disorders such as alcohol consumption, viral hepatitis, or hemochromatosis.[3] Therefore, despite the fact that liver biopsy is considered an invasive test, it is likely that liver biopsy and histologic evaluation of the liver play an important potential role in differential diagnosis. Here, not only do we postulate that hepatic histology is highly effective in diagnosis, but we also hypothesize that characteristic biochemical liver test patterns (including hepatocellular, cholestatic, or mixed patterns) may be associated with specific types of liver diseases.