Gastroenterology

Gastroenterology

Volume 128, Issue 7, June 2005, Pages 1898-1906
Gastroenterology

Clinical-liver, pancreas, and biliary tract
Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease

https://doi.org/10.1053/j.gastro.2005.03.084Get rights and content

Background & Aims: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. Methods: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the κ reliability test. Results: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. Conclusions: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.

Section snippets

Selection Criteria

Consecutive patients with a suspected diagnosis of NAFLD were prospectively enrolled in this study. The diagnosis of NAFLD was based on the following: (1) a bright pattern of the liver on abdominal ultrasound, (2) elevated serum transaminase levels, and (3) no other identifiable causes of liver disease. Other causes of liver disease were ruled out by appropriate work-up: these included daily alcohol consumption greater than 30 g for men and 20 g for women; drug-induced hepatotoxicity; infection

General Description

A total of 51 patients was included in this study: 31 men and 20 women. Their mean age was 54.9 years (range, 31–73 years). Median body mass index was 31.6 kg/m2 (range, 21.6–44.6). All patients had compensated liver disease, and abnormal liver function tests were discovered either fortuitously (24%) or during a work-up for dyslipidemia (43%) or diabetes and dyslipidemia (33%).

Characteristics of the biopsy samples and the main histologic results are given in Table 2. The difference in size

Discussion

This study shows that most NAFLD-related pathologic features display considerable sampling variability when collected through percutaneous liver biopsy. Agreement between the 2 biopsy specimens was only moderate for most features, including hepatocyte ballooning and perisinusoidal fibrosis, whereas, for some others, such as acidophilic bodies, lobular inflammation, or Mallory bodies, the agreement was poor. Only steatosis grade and interface hepatitis displayed substantial agreement between the

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    V.R. and F.C. contributed equally to the study.

    Members of the LIDO (Liver Injury in Diabetes and Obesity) Study Group are: André Grimaldi, Philippe Giral, Eric Bruckert, Gérard Turpin, Agnès Heurtier, Sophie Gombert, Francine Lamaison, Joseph Moussalli, Sophie Le Calvez, Yves Benhamou, Cecilia D’Arrondel, Arnaud Cocaul, Isabelle Ravalet, Stéphanie Combet, Hôpital Pitié Salpêtrière; Philippe Podevin, Hôpital Cochin; Arnaud Basdevant, Gérard Slama, Karine Clement, Hôpital Hotel-Dieu; Lawrence Serfaty, Chantal Housset, Jacqueline Capeau, Hôpital Saint Antoine.

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