Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis

Eric Nguyen-Khac*, Maja Thiele, Cosmin Voican, Pierre Nahon, Christophe Moreno, Jerome Boursier, Sebastian Mueller, Victor de Ledinghen, Peter Stärkel, Sang Gyune Kim, Michael Fernandez, Bjorn Madsen, Sylvie Naveau, Aleksander Krag, Gabriel Perlemuter, Marianne Ziol, Denis Chatelain, Momar Diouf

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Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness. Methods: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis. Findings: Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79–0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82–0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86–0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83–0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (p<0·0001), and with significantly higher cutoff values for diagnosis of all fibrosis stages but F≥1. The presence of histological features of asymptomatic and non-severe alcoholic hepatitis was associated with increased liver stiffness (p<0·0001). In a multivariate analysis, AST (p<0·0001) and bilirubin (p=0·0002) concentrations, and prothrombin activity (p=0·01), were independently associated with the presence of histological features of asymptomatic and non-severe alcoholic hepatitis. Lastly, specific liver stiffness cutoffs were determined on the basis of concentrations of AST and bilirubin. Liver stiffness cutoff values increased in patients with increased AST concentrations, bilirubin concentrations, or both. Interpretation: This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs. Funding: None.

OriginalsprogEngelsk
TidsskriftThe Lancet Gastroenterology and Hepatology
Vol/bind3
Udgave nummer9
Sider (fra-til)614-625
ISSN2468-1253
DOI
StatusUdgivet - 1. sep. 2018

Fingeraftryk

Liver Cirrhosis
Meta-Analysis
Liver Diseases
Alcohols
Alcoholic Hepatitis
Liver
Prothrombin
PubMed
ROC Curve
Multivariate Analysis
Databases

Citer dette

Nguyen-Khac, Eric ; Thiele, Maja ; Voican, Cosmin ; Nahon, Pierre ; Moreno, Christophe ; Boursier, Jerome ; Mueller, Sebastian ; de Ledinghen, Victor ; Stärkel, Peter ; Gyune Kim, Sang ; Fernandez, Michael ; Madsen, Bjorn ; Naveau, Sylvie ; Krag, Aleksander ; Perlemuter, Gabriel ; Ziol, Marianne ; Chatelain, Denis ; Diouf, Momar. / Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography : an individual patient data meta-analysis. I: The Lancet Gastroenterology and Hepatology. 2018 ; Bind 3, Nr. 9. s. 614-625.
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title = "Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis",
abstract = "Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness. Methods: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis. Findings: Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95{\%} CI 0·79–0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82–0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86–0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83–0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (p<0·0001), and with significantly higher cutoff values for diagnosis of all fibrosis stages but F≥1. The presence of histological features of asymptomatic and non-severe alcoholic hepatitis was associated with increased liver stiffness (p<0·0001). In a multivariate analysis, AST (p<0·0001) and bilirubin (p=0·0002) concentrations, and prothrombin activity (p=0·01), were independently associated with the presence of histological features of asymptomatic and non-severe alcoholic hepatitis. Lastly, specific liver stiffness cutoffs were determined on the basis of concentrations of AST and bilirubin. Liver stiffness cutoff values increased in patients with increased AST concentrations, bilirubin concentrations, or both. Interpretation: This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs. Funding: None.",
author = "Eric Nguyen-Khac and Maja Thiele and Cosmin Voican and Pierre Nahon and Christophe Moreno and Jerome Boursier and Sebastian Mueller and {de Ledinghen}, Victor and Peter St{\"a}rkel and {Gyune Kim}, Sang and Michael Fernandez and Bjorn Madsen and Sylvie Naveau and Aleksander Krag and Gabriel Perlemuter and Marianne Ziol and Denis Chatelain and Momar Diouf",
year = "2018",
month = "9",
day = "1",
doi = "10.1016/S2468-1253(18)30124-9",
language = "English",
volume = "3",
pages = "614--625",
journal = "The Lancet Gastroenterology & Hepatology",
issn = "2468-1253",
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Nguyen-Khac, E, Thiele, M, Voican, C, Nahon, P, Moreno, C, Boursier, J, Mueller, S, de Ledinghen, V, Stärkel, P, Gyune Kim, S, Fernandez, M, Madsen, B, Naveau, S, Krag, A, Perlemuter, G, Ziol, M, Chatelain, D & Diouf, M 2018, 'Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis', The Lancet Gastroenterology and Hepatology, bind 3, nr. 9, s. 614-625. https://doi.org/10.1016/S2468-1253(18)30124-9

Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography : an individual patient data meta-analysis. / Nguyen-Khac, Eric; Thiele, Maja; Voican, Cosmin; Nahon, Pierre; Moreno, Christophe; Boursier, Jerome; Mueller, Sebastian; de Ledinghen, Victor; Stärkel, Peter; Gyune Kim, Sang; Fernandez, Michael; Madsen, Bjorn; Naveau, Sylvie; Krag, Aleksander; Perlemuter, Gabriel; Ziol, Marianne; Chatelain, Denis; Diouf, Momar.

I: The Lancet Gastroenterology and Hepatology, Bind 3, Nr. 9, 01.09.2018, s. 614-625.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography

T2 - an individual patient data meta-analysis

AU - Nguyen-Khac, Eric

AU - Thiele, Maja

AU - Voican, Cosmin

AU - Nahon, Pierre

AU - Moreno, Christophe

AU - Boursier, Jerome

AU - Mueller, Sebastian

AU - de Ledinghen, Victor

AU - Stärkel, Peter

AU - Gyune Kim, Sang

AU - Fernandez, Michael

AU - Madsen, Bjorn

AU - Naveau, Sylvie

AU - Krag, Aleksander

AU - Perlemuter, Gabriel

AU - Ziol, Marianne

AU - Chatelain, Denis

AU - Diouf, Momar

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness. Methods: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis. Findings: Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79–0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82–0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86–0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83–0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (p<0·0001), and with significantly higher cutoff values for diagnosis of all fibrosis stages but F≥1. The presence of histological features of asymptomatic and non-severe alcoholic hepatitis was associated with increased liver stiffness (p<0·0001). In a multivariate analysis, AST (p<0·0001) and bilirubin (p=0·0002) concentrations, and prothrombin activity (p=0·01), were independently associated with the presence of histological features of asymptomatic and non-severe alcoholic hepatitis. Lastly, specific liver stiffness cutoffs were determined on the basis of concentrations of AST and bilirubin. Liver stiffness cutoff values increased in patients with increased AST concentrations, bilirubin concentrations, or both. Interpretation: This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs. Funding: None.

AB - Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness. Methods: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis. Findings: Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79–0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82–0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86–0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83–0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (p<0·0001), and with significantly higher cutoff values for diagnosis of all fibrosis stages but F≥1. The presence of histological features of asymptomatic and non-severe alcoholic hepatitis was associated with increased liver stiffness (p<0·0001). In a multivariate analysis, AST (p<0·0001) and bilirubin (p=0·0002) concentrations, and prothrombin activity (p=0·01), were independently associated with the presence of histological features of asymptomatic and non-severe alcoholic hepatitis. Lastly, specific liver stiffness cutoffs were determined on the basis of concentrations of AST and bilirubin. Liver stiffness cutoff values increased in patients with increased AST concentrations, bilirubin concentrations, or both. Interpretation: This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs. Funding: None.

U2 - 10.1016/S2468-1253(18)30124-9

DO - 10.1016/S2468-1253(18)30124-9

M3 - Journal article

AN - SCOPUS:85049423400

VL - 3

SP - 614

EP - 625

JO - The Lancet Gastroenterology & Hepatology

JF - The Lancet Gastroenterology & Hepatology

SN - 2468-1253

IS - 9

ER -