Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis

Thomas Karlas, David Petroff, Magali Sasso, Jian Gao Fan, Yu Qiang Mi, Victor de Lédinghen, Manoj Kumar, Monica Lupsor-Platon, KwangHyub Han, Ana C. Cardoso, Giovanna Ferraioli, Wah Kheong Chan, Vincent Wai Sun Wong, Robert P. Myers, Kazuaki Chayama, Mireen Friedrich-Rust, Michel Beaugrand, Feng Shen, Jean Baptiste Hiriart, Shiv K. Sarin & 12 others Radu Badea, Kyu Sik Jung, Patrick Marcellin, Carlo Filice, Sanjiv Mahadeva, Grace Lai Hung Wong, Pam Crotty, Keiichi Masaki, Joerg Bojunga, Pierre Bedossa, Volker Keim, Johannes Wiegand

Research output: Contribution to journalArticle

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Abstract

Background & Aims The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. Methods A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0–S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. Results Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5–17) for NAFLD/NASH patients, 10 (3.5–16) for diabetics and 4.4 (3.8–5.0) per BMI unit. Areas under the curves were 0.823 (0.809–0.837) and 0.865 (0.850–0.880) respectively. Optimal cut-offs were 248 (237–261) and 268 (257–284) for those above S0 and S1 respectively. Conclusions CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. Lay summary There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

Original languageEnglish
Pages (from-to)1022-1030
Number of pages9
JournalJournal of Hepatology
Volume66
Issue number5
DOIs
Publication statusPublished - 2017 May 1

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Meta-Analysis
Technology
Fatty Liver
Elasticity Imaging Techniques
Liver
Hepatitis C
Vibration
Hepatitis B
ROC Curve
Uncertainty
Area Under Curve
Liver Diseases
Histology
Chronic Disease
Obesity
Biopsy
Non-alcoholic Fatty Liver Disease

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Karlas, T., Petroff, D., Sasso, M., Fan, J. G., Mi, Y. Q., de Lédinghen, V., ... Wiegand, J. (2017). Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. Journal of Hepatology, 66(5), 1022-1030. https://doi.org/10.1016/j.jhep.2016.12.022
Karlas, Thomas ; Petroff, David ; Sasso, Magali ; Fan, Jian Gao ; Mi, Yu Qiang ; de Lédinghen, Victor ; Kumar, Manoj ; Lupsor-Platon, Monica ; Han, KwangHyub ; Cardoso, Ana C. ; Ferraioli, Giovanna ; Chan, Wah Kheong ; Wong, Vincent Wai Sun ; Myers, Robert P. ; Chayama, Kazuaki ; Friedrich-Rust, Mireen ; Beaugrand, Michel ; Shen, Feng ; Hiriart, Jean Baptiste ; Sarin, Shiv K. ; Badea, Radu ; Jung, Kyu Sik ; Marcellin, Patrick ; Filice, Carlo ; Mahadeva, Sanjiv ; Wong, Grace Lai Hung ; Crotty, Pam ; Masaki, Keiichi ; Bojunga, Joerg ; Bedossa, Pierre ; Keim, Volker ; Wiegand, Johannes. / Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. In: Journal of Hepatology. 2017 ; Vol. 66, No. 5. pp. 1022-1030.
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abstract = "Background & Aims The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. Methods A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan{\circledR}) for grading of steatosis (S0–S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. Results Data from 19/21 eligible papers were provided, comprising 3830/3968 (97{\%}) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37{\%} hepatitis B, 36{\%} hepatitis C, 20{\%} NAFLD/NASH, 7{\%} other). Steatosis distribution was 51{\%}/27{\%}/16{\%}/6{\%} for S0/S1/S2/S3. CAP values in dB/m (95{\%} CI) were influenced by several covariates with an estimated shift of 10 (4.5–17) for NAFLD/NASH patients, 10 (3.5–16) for diabetics and 4.4 (3.8–5.0) per BMI unit. Areas under the curves were 0.823 (0.809–0.837) and 0.865 (0.850–0.880) respectively. Optimal cut-offs were 248 (237–261) and 268 (257–284) for those above S0 and S1 respectively. Conclusions CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. Lay summary There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.",
author = "Thomas Karlas and David Petroff and Magali Sasso and Fan, {Jian Gao} and Mi, {Yu Qiang} and {de L{\'e}dinghen}, Victor and Manoj Kumar and Monica Lupsor-Platon and KwangHyub Han and Cardoso, {Ana C.} and Giovanna Ferraioli and Chan, {Wah Kheong} and Wong, {Vincent Wai Sun} and Myers, {Robert P.} and Kazuaki Chayama and Mireen Friedrich-Rust and Michel Beaugrand and Feng Shen and Hiriart, {Jean Baptiste} and Sarin, {Shiv K.} and Radu Badea and Jung, {Kyu Sik} and Patrick Marcellin and Carlo Filice and Sanjiv Mahadeva and Wong, {Grace Lai Hung} and Pam Crotty and Keiichi Masaki and Joerg Bojunga and Pierre Bedossa and Volker Keim and Johannes Wiegand",
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Karlas, T, Petroff, D, Sasso, M, Fan, JG, Mi, YQ, de Lédinghen, V, Kumar, M, Lupsor-Platon, M, Han, K, Cardoso, AC, Ferraioli, G, Chan, WK, Wong, VWS, Myers, RP, Chayama, K, Friedrich-Rust, M, Beaugrand, M, Shen, F, Hiriart, JB, Sarin, SK, Badea, R, Jung, KS, Marcellin, P, Filice, C, Mahadeva, S, Wong, GLH, Crotty, P, Masaki, K, Bojunga, J, Bedossa, P, Keim, V & Wiegand, J 2017, 'Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis', Journal of Hepatology, vol. 66, no. 5, pp. 1022-1030. https://doi.org/10.1016/j.jhep.2016.12.022

Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. / Karlas, Thomas; Petroff, David; Sasso, Magali; Fan, Jian Gao; Mi, Yu Qiang; de Lédinghen, Victor; Kumar, Manoj; Lupsor-Platon, Monica; Han, KwangHyub; Cardoso, Ana C.; Ferraioli, Giovanna; Chan, Wah Kheong; Wong, Vincent Wai Sun; Myers, Robert P.; Chayama, Kazuaki; Friedrich-Rust, Mireen; Beaugrand, Michel; Shen, Feng; Hiriart, Jean Baptiste; Sarin, Shiv K.; Badea, Radu; Jung, Kyu Sik; Marcellin, Patrick; Filice, Carlo; Mahadeva, Sanjiv; Wong, Grace Lai Hung; Crotty, Pam; Masaki, Keiichi; Bojunga, Joerg; Bedossa, Pierre; Keim, Volker; Wiegand, Johannes.

In: Journal of Hepatology, Vol. 66, No. 5, 01.05.2017, p. 1022-1030.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis

AU - Karlas, Thomas

AU - Petroff, David

AU - Sasso, Magali

AU - Fan, Jian Gao

AU - Mi, Yu Qiang

AU - de Lédinghen, Victor

AU - Kumar, Manoj

AU - Lupsor-Platon, Monica

AU - Han, KwangHyub

AU - Cardoso, Ana C.

AU - Ferraioli, Giovanna

AU - Chan, Wah Kheong

AU - Wong, Vincent Wai Sun

AU - Myers, Robert P.

AU - Chayama, Kazuaki

AU - Friedrich-Rust, Mireen

AU - Beaugrand, Michel

AU - Shen, Feng

AU - Hiriart, Jean Baptiste

AU - Sarin, Shiv K.

AU - Badea, Radu

AU - Jung, Kyu Sik

AU - Marcellin, Patrick

AU - Filice, Carlo

AU - Mahadeva, Sanjiv

AU - Wong, Grace Lai Hung

AU - Crotty, Pam

AU - Masaki, Keiichi

AU - Bojunga, Joerg

AU - Bedossa, Pierre

AU - Keim, Volker

AU - Wiegand, Johannes

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Background & Aims The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. Methods A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0–S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. Results Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5–17) for NAFLD/NASH patients, 10 (3.5–16) for diabetics and 4.4 (3.8–5.0) per BMI unit. Areas under the curves were 0.823 (0.809–0.837) and 0.865 (0.850–0.880) respectively. Optimal cut-offs were 248 (237–261) and 268 (257–284) for those above S0 and S1 respectively. Conclusions CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. Lay summary There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

AB - Background & Aims The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. Methods A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0–S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. Results Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5–17) for NAFLD/NASH patients, 10 (3.5–16) for diabetics and 4.4 (3.8–5.0) per BMI unit. Areas under the curves were 0.823 (0.809–0.837) and 0.865 (0.850–0.880) respectively. Optimal cut-offs were 248 (237–261) and 268 (257–284) for those above S0 and S1 respectively. Conclusions CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. Lay summary There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

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