Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: Distinct clinicopathologic meanings

Elizabeth M Brunt, David E Kleiner, Laura A Wilson, Patricia Belt, Brent A Neuschwander-Tetri, Bradley Aouizerat, NASH Clinical Research Network (CRN)

Research output: Contribution to journalArticle

Abstract

UNLABELLED: The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD during therapeutic trials. However, some studies have used threshold values of the NAS, specifically NAS ≥5, as a surrogate for the histologic diagnosis of NASH. To evaluate whether this unintended use of the NAS is valid, biopsy and clinical data from the 976 adults in NASH Clinical Research Network (CRN) studies were reviewed. Biopsies were evaluated centrally by the NASH CRN Pathology Committee. Definite steatohepatitis (SH) was diagnosed in 58.1%, borderline SH in 19.5% and "not SH" in 22%. The NAS was ≥5 in 50% and ≤4 in 49%; in this cohort only 75% of biopsies with definite SH had an NAS ≥5, whereas 28% of borderline SH and 7% of "not SH" biopsies had NAS ≥5. Of biopsies with an NAS ≥5, 86% had SH and 3% "not SH". NAS ≤4 did not indicate benign histology; 29% had SH and only 42% had "not SH." Higher values of the NAS were associated with higher levels of alanine aminotransferase and aspartate aminotransferase, whereas the diagnosis of SH was associated with features of the metabolic syndrome.

CONCLUSION: The diagnosis of definite SH or the absence of SH based on evaluation of patterns as well as individual lesions on liver biopsies does not always correlate with threshold values of the semiquantitative NAS. Clinical trials and observational studies should take these different performance characteristics into account.

Original languageEnglish (US)
Pages (from-to)810-20
Number of pages11
JournalHepatology
Volume53
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

Fatty Liver
Biopsy
Non-alcoholic Fatty Liver Disease
Liver
Aspartate Aminotransferases
Alanine Transaminase
Research
Observational Studies
Histology
Clinical Trials
Pathology

Keywords

  • Adolescent
  • Adult
  • Aged
  • Alanine Transaminase
  • Aspartate Aminotransferases
  • Biopsy
  • Fatty Liver
  • Female
  • Humans
  • Liver
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Prospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index

Cite this

Brunt, E. M., Kleiner, D. E., Wilson, L. A., Belt, P., Neuschwander-Tetri, B. A., Aouizerat, B., & NASH Clinical Research Network (CRN) (2011). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: Distinct clinicopathologic meanings. Hepatology, 53(3), 810-20. https://doi.org/10.1002/hep.24127

Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD : Distinct clinicopathologic meanings. / Brunt, Elizabeth M; Kleiner, David E; Wilson, Laura A; Belt, Patricia; Neuschwander-Tetri, Brent A; Aouizerat, Bradley; NASH Clinical Research Network (CRN).

In: Hepatology, Vol. 53, No. 3, 03.2011, p. 810-20.

Research output: Contribution to journalArticle

Brunt, EM, Kleiner, DE, Wilson, LA, Belt, P, Neuschwander-Tetri, BA, Aouizerat, B & NASH Clinical Research Network (CRN) 2011, 'Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: Distinct clinicopathologic meanings', Hepatology, vol. 53, no. 3, pp. 810-20. https://doi.org/10.1002/hep.24127
Brunt, Elizabeth M ; Kleiner, David E ; Wilson, Laura A ; Belt, Patricia ; Neuschwander-Tetri, Brent A ; Aouizerat, Bradley ; NASH Clinical Research Network (CRN). / Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD : Distinct clinicopathologic meanings. In: Hepatology. 2011 ; Vol. 53, No. 3. pp. 810-20.
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abstract = "UNLABELLED: The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD during therapeutic trials. However, some studies have used threshold values of the NAS, specifically NAS ≥5, as a surrogate for the histologic diagnosis of NASH. To evaluate whether this unintended use of the NAS is valid, biopsy and clinical data from the 976 adults in NASH Clinical Research Network (CRN) studies were reviewed. Biopsies were evaluated centrally by the NASH CRN Pathology Committee. Definite steatohepatitis (SH) was diagnosed in 58.1{\%}, borderline SH in 19.5{\%} and {"}not SH{"} in 22{\%}. The NAS was ≥5 in 50{\%} and ≤4 in 49{\%}; in this cohort only 75{\%} of biopsies with definite SH had an NAS ≥5, whereas 28{\%} of borderline SH and 7{\%} of {"}not SH{"} biopsies had NAS ≥5. Of biopsies with an NAS ≥5, 86{\%} had SH and 3{\%} {"}not SH{"}. NAS ≤4 did not indicate benign histology; 29{\%} had SH and only 42{\%} had {"}not SH.{"} Higher values of the NAS were associated with higher levels of alanine aminotransferase and aspartate aminotransferase, whereas the diagnosis of SH was associated with features of the metabolic syndrome.CONCLUSION: The diagnosis of definite SH or the absence of SH based on evaluation of patterns as well as individual lesions on liver biopsies does not always correlate with threshold values of the semiquantitative NAS. Clinical trials and observational studies should take these different performance characteristics into account.",
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T1 - Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD

T2 - Distinct clinicopathologic meanings

AU - Brunt, Elizabeth M

AU - Kleiner, David E

AU - Wilson, Laura A

AU - Belt, Patricia

AU - Neuschwander-Tetri, Brent A

AU - Aouizerat, Bradley

AU - NASH Clinical Research Network (CRN)

N1 - Copyright © 2010 American Association for the Study of Liver Diseases.

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N2 - UNLABELLED: The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD during therapeutic trials. However, some studies have used threshold values of the NAS, specifically NAS ≥5, as a surrogate for the histologic diagnosis of NASH. To evaluate whether this unintended use of the NAS is valid, biopsy and clinical data from the 976 adults in NASH Clinical Research Network (CRN) studies were reviewed. Biopsies were evaluated centrally by the NASH CRN Pathology Committee. Definite steatohepatitis (SH) was diagnosed in 58.1%, borderline SH in 19.5% and "not SH" in 22%. The NAS was ≥5 in 50% and ≤4 in 49%; in this cohort only 75% of biopsies with definite SH had an NAS ≥5, whereas 28% of borderline SH and 7% of "not SH" biopsies had NAS ≥5. Of biopsies with an NAS ≥5, 86% had SH and 3% "not SH". NAS ≤4 did not indicate benign histology; 29% had SH and only 42% had "not SH." Higher values of the NAS were associated with higher levels of alanine aminotransferase and aspartate aminotransferase, whereas the diagnosis of SH was associated with features of the metabolic syndrome.CONCLUSION: The diagnosis of definite SH or the absence of SH based on evaluation of patterns as well as individual lesions on liver biopsies does not always correlate with threshold values of the semiquantitative NAS. Clinical trials and observational studies should take these different performance characteristics into account.

AB - UNLABELLED: The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD during therapeutic trials. However, some studies have used threshold values of the NAS, specifically NAS ≥5, as a surrogate for the histologic diagnosis of NASH. To evaluate whether this unintended use of the NAS is valid, biopsy and clinical data from the 976 adults in NASH Clinical Research Network (CRN) studies were reviewed. Biopsies were evaluated centrally by the NASH CRN Pathology Committee. Definite steatohepatitis (SH) was diagnosed in 58.1%, borderline SH in 19.5% and "not SH" in 22%. The NAS was ≥5 in 50% and ≤4 in 49%; in this cohort only 75% of biopsies with definite SH had an NAS ≥5, whereas 28% of borderline SH and 7% of "not SH" biopsies had NAS ≥5. Of biopsies with an NAS ≥5, 86% had SH and 3% "not SH". NAS ≤4 did not indicate benign histology; 29% had SH and only 42% had "not SH." Higher values of the NAS were associated with higher levels of alanine aminotransferase and aspartate aminotransferase, whereas the diagnosis of SH was associated with features of the metabolic syndrome.CONCLUSION: The diagnosis of definite SH or the absence of SH based on evaluation of patterns as well as individual lesions on liver biopsies does not always correlate with threshold values of the semiquantitative NAS. Clinical trials and observational studies should take these different performance characteristics into account.

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KW - Adult

KW - Aged

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KW - Aspartate Aminotransferases

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KW - Fatty Liver

KW - Female

KW - Humans

KW - Liver

KW - Male

KW - Middle Aged

KW - Non-alcoholic Fatty Liver Disease

KW - Prospective Studies

KW - Sensitivity and Specificity

KW - Severity of Illness Index

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JO - Hepatology

JF - Hepatology

SN - 0270-9139

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ER -