- •
Liver biopsy remains the gold standard for the diagnosis of nonalcoholic fatty liver and is currently the only modality that can reliably differentiate benign fatty liver from nonalcoholic steatohepatitis.
- •
Liver biopsy remains a valuable tool for the assessment of liver disease progression or regression in patients with nonalcoholic steatohepatitis.
- •
Liver biopsy is the only tool that can correctly differentiate which process may be causing liver injury in patients with clinical features of the
The Use of Liver Biopsy in Nonalcoholic Fatty Liver Disease: When to Biopsy and in Whom
Section snippets
Key points
Natural history and clinical features of nonalcoholic fatty liver disease
NAFLD can be divided into 2 categories: benign steatosis, also referred to as isolated fatty liver or NAFL, and NASH. NAFL is present in about 66% to 80% of patients with NAFLD.1, 2, 4 Long-term studies have demonstrated that patients with NAFL have less than a 1% chance of developing fibrosis progression to cirrhosis or liver-related mortality over 15 years.17, 18, 19, 20, 21 Long-term survival is similar to that of the general population. In contrast, 20% to 33% of patients with NAFLD have
Recognition of patients with nonalcoholic fatty liver disease
An elevation in serum liver transaminases, either aspartate transaminase (AST) and/or alanine transaminase (ALT), is often the first hint that patients may have NAFLD. Serologic studies should be performed in such patients to exclude all other causes of chronic liver disease. NAFLD is suspected when all serologic studies are negative. However, many patients with NAFLD may have a moderate elevation in serum ferritin, some have a positive antinuclear (ANA) smooth muscle antibody (ASMA), and
Noninvasive markers of nonalcoholic fatty liver disease
Once patients are suspected of having NAFLD, several noninvasive tests can be used to help confirm this is correct and to determine if this is NAFL or NASH. Cytokeratin (CK)-18 is a serum marker that is increased in patients with hepatocyte apoptosis and is thought to be relatively specific for NASH as opposed to being a general marker of apoptosis from other forms of chronic liver disease. Elevations in CK-18 greater than 210 u/L are suggestive of NASH.32, 37 Unfortunately, CK-18 is not a
What is learned by performing liver biopsy in patients with suspected nonalcoholic fatty liver disease
The goals of performing a liver biopsy in patients suspected of having NAFLD are to confirm this diagnosis, exclude other causes of chronic liver disease, determine if patients have NAFL or NASH, and to demonstrate if patients have cirrhosis. A diagnosis of NAFLD requires that there is at last 5% steatosis in the liver biopsy specimen.1, 2, 3 The NAFLD Activity Score (NAS) is a useful system to assess liver injury in patients with NAFLD and response to therapy for patients enrolled in clinical
In whom and when should a liver biopsy be performed
It is not necessary to perform a liver biopsy in all patients suspected of having NAFLD.15, 16 A liver biopsy should only be performed if it will alter your treatment recommendations for patients, make patients aware they have a serious liver condition, or to confirm or exclude NAFLD in patients with conflicting clinical data. The data that you should use to decide on whether to perform a liver biopsy include liver transaminases, liver ultrasound, serologic studies for other causes of liver
Summary
NAFLD is common in the United States and throughout the world and leads to cirrhosis in a significant percentage of patients. Most patients with NAFLD are identified because they are found to have a liver ultrasound or other imaging study suggesting fatty liver with or without an elevation in liver transaminases. A presumptive diagnosis of NAFLD is correct once other causes of chronic liver disease have been excluded with appropriate serologic testing. NAFLD can exist as NAFL, which does not
References (55)
- et al.
Obesity-associated nonalcoholic fatty liver disease
Clin Liver Dis
(2014) - et al.
Histology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in adults and children
Clin Liver Dis
(2016) - et al.
Nonalcoholic fatty liver disease
Clin Liver Dis
(2012) - et al.
Can NASH be diagnosed, graded and staged non-invasively?
Clin Liver Dis
(2012) - et al.
Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease
J Hepatol
(2011) - et al.
The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology
Gastroenterology
(2012) - et al.
A position statement on NAFLD/NASH based on the EASL 2009 special conference
J Hepatol
(2010) - et al.
Liver fibrosis but no other histologic features, is associated with long term outcomes of patients with non alcoholic fatty liver disease
Gastroenterology
(2015) - et al.
Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome
Hepatology
(2003) - et al.
The metabolic syndrome and its influence on nonalcoholic steatohepatitis
Clin Liver Dis
(2016)
Behavior and significance of autoantibodies in type 1 autoimmune hepatitis
J Hepatol
Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology
J Hepatol
Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study
Gastroenterology
Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values
Hepatology
Discordance in fibrosis staging between liver biopsy and transient elastography using the FibroScan XL probe
J Hepatol
MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: clinical trials to clinical practice
J Hepatol
Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions
Am J Gastroenterol
Effect of weight loss, diet, exercise, and bariatric surgery on nonalcoholic fatty liver disease
Clin Liver Dis
Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease
J Hepatol
Impact of liver biopsy size on the histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease
J Hepatol
Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies
J Hepatol
Sampling variability of liver biopsy in nonalcoholic fatty liver disease
Gastroenterology
The epidemiology of nonalcoholic fatty liver disease: a global perspective
Semin Liver Dis
Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity
Ann Med
Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients
Hepatology
Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, Fibro Scan, and ARFI with liver biopsy
Hepatology
Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease
J Gastroenterol Hepatol
Cited by (0)
Disclosure Statement: Dr N.T. Gunn has received research grant support from Conatus, CymaBay, Galectin, Gilead, and Immuron and has received speaker fees from Abbvie, Gilead, and Salix. Dr M.L. Shiffman receives research grant support from Abbvie, BMS, Conatus, CymaBay, Exalenz, Galectin, Genfit, Gilead, Intercept, Immuron, Merck, NGMBio, Novartis, and Shire; is an advisor to Abbvie, BMS, Gilead, Merck, Optum Rx, and Salix; and has received speaker fees from Abbvie, Bayer, BMS, Daiichi-Sankyo, Gilead, Intercept, and Merck.