Validity of noninvasive markers of methotrexate-induced hepatotoxicity: a retrospective cohort study

C L Martyn-Simmons; W M C Rosenberg; R Cross; T Wong; C H Smith; J N W N Barker

doi:10.1111/bjd.12782

Validity of noninvasive markers of methotrexate-induced hepatotoxicity: a retrospective cohort study

C L Martyn-Simmons, W M C Rosenberg, R Cross, T Wong, C H Smith, J N W N Barker

Dermatology

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

BACKGROUND: Methotrexate is a cost-effective systemic treatment for moderate-to-severe psoriasis, but the perceived risk of associated liver fibrosis prevents optimal use. Procollagen III aminoterminal propeptide (PIIINP) is a widely adopted noninvasive biomarker of liver fibrosis; however, its clinical utility is narrow owing to limited evidence of performance and the need for serial measurement. The Enhanced Liver Fibrosis (ELF) assay is a validated biomarker of liver fibrosis.

OBJECTIVES: To evaluate the diagnostic accuracy of the ELF test compared with PIIINP for the diagnosis of liver fibrosis in a cohort of patients with psoriasis treated with methotrexate.

METHODS: A retrospective cohort study comparing the diagnostic accuracy of PIIINP and ELF in detecting liver fibrosis in patients treated with methotrexate. Liver biopsy was the reference standard.

RESULTS: Twenty-seven patients were identified and included in the study. The diagnostic accuracies [area under the receiver operating curve (AUROC)] of serial PIIINP and serial ELF were 0·589 [95% confidence interval (CI) 0·379-0·800] and 0·643 (95% CI 0·391-0·895), respectively, for mild fibrosis; and 0·576 (95% CI 0·237-0·916) and 0·674 (95% CI 0·421-0·927) for at least moderate fibrosis. The AUROC values for single PIIINP and single ELF were 0·582 (95% CI 0·363-0·801) and 0·693 (95% CI 0·482-0·904), respectively, for mild fibrosis; and 0·667 (95% CI 0·363-0·971) and 0·806 (95% CI 0·564-1·000) for at least moderate fibrosis.

CONCLUSIONS: This pilot study suggests that ELF may be at least equivalent or possibly superior to PIIINP in the detection of liver fibrosis in patients with psoriasis treated with methotrexate, and supports further investigations into the performance of ELF in this clinical setting.

Original language	English
Pages (from-to)	267-73
Number of pages	7
Journal	British Journal of Dermatology
Volume	171
Issue number	2
DOIs	https://doi.org/10.1111/bjd.12782
Publication status	Published - Aug 2014

Keywords

Adult
Aged
Biomarkers
Chemical and Drug Induced Liver Injury
Dermatologic Agents
Female
Humans
Life Style
Liver Cirrhosis
Male
Methotrexate
Middle Aged
Peptide Fragments
Pilot Projects
Procollagen
Psoriasis
ROC Curve
Retrospective Studies

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10.1111/bjd.12782

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@article{e020d08920c340f4a143b5b6f54fa9a2,

title = "Validity of noninvasive markers of methotrexate-induced hepatotoxicity: a retrospective cohort study",

abstract = "BACKGROUND: Methotrexate is a cost-effective systemic treatment for moderate-to-severe psoriasis, but the perceived risk of associated liver fibrosis prevents optimal use. Procollagen III aminoterminal propeptide (PIIINP) is a widely adopted noninvasive biomarker of liver fibrosis; however, its clinical utility is narrow owing to limited evidence of performance and the need for serial measurement. The Enhanced Liver Fibrosis (ELF) assay is a validated biomarker of liver fibrosis.OBJECTIVES: To evaluate the diagnostic accuracy of the ELF test compared with PIIINP for the diagnosis of liver fibrosis in a cohort of patients with psoriasis treated with methotrexate.METHODS: A retrospective cohort study comparing the diagnostic accuracy of PIIINP and ELF in detecting liver fibrosis in patients treated with methotrexate. Liver biopsy was the reference standard.RESULTS: Twenty-seven patients were identified and included in the study. The diagnostic accuracies [area under the receiver operating curve (AUROC)] of serial PIIINP and serial ELF were 0·589 [95% confidence interval (CI) 0·379-0·800] and 0·643 (95% CI 0·391-0·895), respectively, for mild fibrosis; and 0·576 (95% CI 0·237-0·916) and 0·674 (95% CI 0·421-0·927) for at least moderate fibrosis. The AUROC values for single PIIINP and single ELF were 0·582 (95% CI 0·363-0·801) and 0·693 (95% CI 0·482-0·904), respectively, for mild fibrosis; and 0·667 (95% CI 0·363-0·971) and 0·806 (95% CI 0·564-1·000) for at least moderate fibrosis.CONCLUSIONS: This pilot study suggests that ELF may be at least equivalent or possibly superior to PIIINP in the detection of liver fibrosis in patients with psoriasis treated with methotrexate, and supports further investigations into the performance of ELF in this clinical setting.",

keywords = "Adult, Aged, Biomarkers, Chemical and Drug Induced Liver Injury, Dermatologic Agents, Female, Humans, Life Style, Liver Cirrhosis, Male, Methotrexate, Middle Aged, Peptide Fragments, Pilot Projects, Procollagen, Psoriasis, ROC Curve, Retrospective Studies",

author = "Martyn-Simmons, {C L} and Rosenberg, {W M C} and R Cross and T Wong and Smith, {C H} and Barker, {J N W N}",

note = "{\textcopyright} 2014 British Association of Dermatologists.",

year = "2014",

month = aug,

doi = "10.1111/bjd.12782",

language = "English",

volume = "171",

pages = "267--73",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "John Wiley & Sons, Ltd (10.1111)",

number = "2",

}

TY - JOUR

T1 - Validity of noninvasive markers of methotrexate-induced hepatotoxicity

T2 - a retrospective cohort study

AU - Martyn-Simmons, C L

AU - Rosenberg, W M C

AU - Cross, R

AU - Wong, T

AU - Smith, C H

AU - Barker, J N W N

PY - 2014/8

Y1 - 2014/8

N2 - BACKGROUND: Methotrexate is a cost-effective systemic treatment for moderate-to-severe psoriasis, but the perceived risk of associated liver fibrosis prevents optimal use. Procollagen III aminoterminal propeptide (PIIINP) is a widely adopted noninvasive biomarker of liver fibrosis; however, its clinical utility is narrow owing to limited evidence of performance and the need for serial measurement. The Enhanced Liver Fibrosis (ELF) assay is a validated biomarker of liver fibrosis.OBJECTIVES: To evaluate the diagnostic accuracy of the ELF test compared with PIIINP for the diagnosis of liver fibrosis in a cohort of patients with psoriasis treated with methotrexate.METHODS: A retrospective cohort study comparing the diagnostic accuracy of PIIINP and ELF in detecting liver fibrosis in patients treated with methotrexate. Liver biopsy was the reference standard.RESULTS: Twenty-seven patients were identified and included in the study. The diagnostic accuracies [area under the receiver operating curve (AUROC)] of serial PIIINP and serial ELF were 0·589 [95% confidence interval (CI) 0·379-0·800] and 0·643 (95% CI 0·391-0·895), respectively, for mild fibrosis; and 0·576 (95% CI 0·237-0·916) and 0·674 (95% CI 0·421-0·927) for at least moderate fibrosis. The AUROC values for single PIIINP and single ELF were 0·582 (95% CI 0·363-0·801) and 0·693 (95% CI 0·482-0·904), respectively, for mild fibrosis; and 0·667 (95% CI 0·363-0·971) and 0·806 (95% CI 0·564-1·000) for at least moderate fibrosis.CONCLUSIONS: This pilot study suggests that ELF may be at least equivalent or possibly superior to PIIINP in the detection of liver fibrosis in patients with psoriasis treated with methotrexate, and supports further investigations into the performance of ELF in this clinical setting.

AB - BACKGROUND: Methotrexate is a cost-effective systemic treatment for moderate-to-severe psoriasis, but the perceived risk of associated liver fibrosis prevents optimal use. Procollagen III aminoterminal propeptide (PIIINP) is a widely adopted noninvasive biomarker of liver fibrosis; however, its clinical utility is narrow owing to limited evidence of performance and the need for serial measurement. The Enhanced Liver Fibrosis (ELF) assay is a validated biomarker of liver fibrosis.OBJECTIVES: To evaluate the diagnostic accuracy of the ELF test compared with PIIINP for the diagnosis of liver fibrosis in a cohort of patients with psoriasis treated with methotrexate.METHODS: A retrospective cohort study comparing the diagnostic accuracy of PIIINP and ELF in detecting liver fibrosis in patients treated with methotrexate. Liver biopsy was the reference standard.RESULTS: Twenty-seven patients were identified and included in the study. The diagnostic accuracies [area under the receiver operating curve (AUROC)] of serial PIIINP and serial ELF were 0·589 [95% confidence interval (CI) 0·379-0·800] and 0·643 (95% CI 0·391-0·895), respectively, for mild fibrosis; and 0·576 (95% CI 0·237-0·916) and 0·674 (95% CI 0·421-0·927) for at least moderate fibrosis. The AUROC values for single PIIINP and single ELF were 0·582 (95% CI 0·363-0·801) and 0·693 (95% CI 0·482-0·904), respectively, for mild fibrosis; and 0·667 (95% CI 0·363-0·971) and 0·806 (95% CI 0·564-1·000) for at least moderate fibrosis.CONCLUSIONS: This pilot study suggests that ELF may be at least equivalent or possibly superior to PIIINP in the detection of liver fibrosis in patients with psoriasis treated with methotrexate, and supports further investigations into the performance of ELF in this clinical setting.

KW - Adult

KW - Aged

KW - Biomarkers

KW - Chemical and Drug Induced Liver Injury

KW - Dermatologic Agents

KW - Female

KW - Humans

KW - Life Style

KW - Liver Cirrhosis

KW - Male

KW - Methotrexate

KW - Middle Aged

KW - Peptide Fragments

KW - Pilot Projects

KW - Procollagen

KW - Psoriasis

KW - ROC Curve

KW - Retrospective Studies

U2 - 10.1111/bjd.12782

DO - 10.1111/bjd.12782

M3 - Article

C2 - 24942271

SN - 0007-0963

VL - 171

SP - 267

EP - 273

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 2

ER -

Validity of noninvasive markers of methotrexate-induced hepatotoxicity: a retrospective cohort study

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Keywords

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