Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH

Eduardo Vilar-Gomez, Luis Calzadilla-Bertot, Scott L. Friedman, Bienvenido Gra-Oramas, Licet Gonzalez-Fabian, Sacha Lazo-del Vallin, Moises Diago, Leon A. Adams

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    12 Citations (Scopus)

    Abstract

    Background & Aims: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Methods: Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Results: Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. Conclusions: Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.

    Original languageEnglish
    Pages (from-to)1887-1896
    Number of pages10
    JournalLiver International
    Volume37
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2017

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    Liver Cirrhosis
    Life Style
    Fibrosis
    Biomarkers
    Biopsy
    Serum
    Blood Platelets
    Liver
    Area Under Curve

    Cite this

    Vilar-Gomez, Eduardo ; Calzadilla-Bertot, Luis ; Friedman, Scott L. ; Gra-Oramas, Bienvenido ; Gonzalez-Fabian, Licet ; Lazo-del Vallin, Sacha ; Diago, Moises ; Adams, Leon A. / Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH. In: Liver International. 2017 ; Vol. 37, No. 12. pp. 1887-1896.
    @article{34e5537fb1604b1591a5e693d78491b1,
    title = "Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH",
    abstract = "Background & Aims: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Methods: Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Results: Regression, stabilization and worsening of fibrosis occurred in 51 (20{\%}), 165 (63{\%}) and 45 (17{\%}) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95{\%} CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94{\%} (95{\%} CI, 84-98) and 91{\%} (95{\%} CI, 81-96) respectively. Conclusions: Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.",
    keywords = "fibrosis regression, lifestyle interventions, nonalcoholic steatohepatitis, noninvasive biomarkers",
    author = "Eduardo Vilar-Gomez and Luis Calzadilla-Bertot and Friedman, {Scott L.} and Bienvenido Gra-Oramas and Licet Gonzalez-Fabian and {Lazo-del Vallin}, Sacha and Moises Diago and Adams, {Leon A.}",
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    Vilar-Gomez, E, Calzadilla-Bertot, L, Friedman, SL, Gra-Oramas, B, Gonzalez-Fabian, L, Lazo-del Vallin, S, Diago, M & Adams, LA 2017, 'Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH' Liver International, vol. 37, no. 12, pp. 1887-1896. https://doi.org/10.1111/liv.13480

    Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH. / Vilar-Gomez, Eduardo; Calzadilla-Bertot, Luis; Friedman, Scott L.; Gra-Oramas, Bienvenido; Gonzalez-Fabian, Licet; Lazo-del Vallin, Sacha; Diago, Moises; Adams, Leon A.

    In: Liver International, Vol. 37, No. 12, 01.12.2017, p. 1887-1896.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH

    AU - Vilar-Gomez, Eduardo

    AU - Calzadilla-Bertot, Luis

    AU - Friedman, Scott L.

    AU - Gra-Oramas, Bienvenido

    AU - Gonzalez-Fabian, Licet

    AU - Lazo-del Vallin, Sacha

    AU - Diago, Moises

    AU - Adams, Leon A.

    PY - 2017/12/1

    Y1 - 2017/12/1

    N2 - Background & Aims: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Methods: Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Results: Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. Conclusions: Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.

    AB - Background & Aims: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Methods: Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Results: Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. Conclusions: Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.

    KW - fibrosis regression

    KW - lifestyle interventions

    KW - nonalcoholic steatohepatitis

    KW - noninvasive biomarkers

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    U2 - 10.1111/liv.13480

    DO - 10.1111/liv.13480

    M3 - Article

    VL - 37

    SP - 1887

    EP - 1896

    JO - Liver International

    JF - Liver International

    SN - 1478-3223

    IS - 12

    ER -