Validation of the Blood Test MACK-3 for the Noninvasive Diagnosis of Fibrotic Nonalcoholic Steatohepatitis: An International Study With 1924 Patients

被引：11

作者：

Canivet, Clemence M. ^{[1
,2
]}

Zheng, Ming-Hua ^{[2
,3
]}

Qadri, Sami ^{[4
,5
]}

Vonghia, Luisa ^{[6
]}

Chuah, Kee-Huat ^{[7
,8
]}

Costentin, Charlotte ^{[9
]}

George, Jacob ^{[10
]}

Armandi, Angelo

Adams, Leon A. ^{[1
,12
]}

Lange, Naomi F. ^{[2
,13
,14
]}

Blanchet, Odile ^{[4
,15
]}

Moal, Valerie ^{[16
]}

Younes, Ramy ^{[11
]}

Roux, Marine ^{[1
]}

Chan, Wah-Kheong ^{[7
,8
]}

Sturm, Nathalie ^{[17
]}

Eslam, Mohammed ^{[10
]}

Bugianesi, Elisabetta

Wang, Zhengyi ^{[1
]}

Dufour, Jean-Francois ^{[18
,19
]}

Francque, Sven ^{[6
]}

Yki-Jaervinen, Hannele ^{[4
,5
]}

Zheng, Kenneth I. ^{[3
]}

Boursier, Jerome ^{[1
,2
,20
]}

机构：

[1] Hop Univ Angers, Serv Hepatogastroenterol & Oncol Digest, Angers, France

[2] Univ Angers, Lab HIFIH, UPRES EA3859, SFR ICAT 4208, Angers, France

[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Hepatol, Nonalcohol Fatty Liver Dis Res Ctr, Wenzhou, Zhejiang, Peoples R China

[4] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland

[5] Univ Hosp Helsinki, Minerva Fdn Inst Med Res, Helsinki, Finland

[6] Antwerp Univ Hosp, Dept Gastroenterol & Hepatol, Antwerp, Belgium

[7] Univ Antwerp, Fac Med & Hlth Sci, Div Gastroenterol, Lab Expt Med & Pediat, Antwerp, Belgium

[8] Univ Malaya, Fac Med, Dept Med, Gastroenterol & Hepatol Unit, Kuala Lumpur, Malaysia

[9] Univ Grenoble Alpes, Grenoble Inst Adv Biosci Res Ctr, Ctr Hosp Univ Grenoble Alpes, Serv Hepato Gastroenterol,UGA,Inserm,CNRS 1209 530, Grenoble, France

[10] Univ Sydney, Westmead Hosp, Storr Liver Ctr, Sydney, NSW, Australia

[11] Univ Torino, Dipartimento Sci Med, Turin, Italy

[12] Univ Western Australia, Med Sch, Perth, Australia

[13] Univ Bern, Univ Hosp Bern, Dept Visceral Surg & Med, Inselspital, Bern, Switzerland

[14] Univ Bern, Grad Sch Hlth Sci, Bern, Switzerland

[15] Angers Univ Hosp, CRB BB 0033 00038, Angers, France

[16] Angers Univ Hosp, Dept Biochem, Angers, France

[17] Ctr Hosp Univ Grenoble Alpes, Serv Anat & Cytol Pathol, La Tronche, France

[18] Ctr Malad Digest, Lausanne, Switzerland

[19] Swiss Nonalcohol Steatohepatitis Fdn, Bern, Switzerland

[20] CHU Angers, Serv Radiol, 4 Rue Larrey, Angers 49933, France

来源：

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY | 2023年 / 21卷 / 12期

关键词：

NAFLD; NASH; Fibrotic NASH; Blood Test; FAST; PROSPECTIVE DERIVATION; FIBROSIS; SCORE; PREVALENCE;

D O I：

10.1016/j.cgh.2023.03.032

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: Drug development in nonalcoholic steatohepatitis (NASH) is hampered by a high screening failure rate that reaches 60% to 80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including 3 biomarkers (aspartate aminotransferase, homeostasis model assessment, and cytokeratin 18), recently was developed for the noninvasive diagnosis of fibrotic NASH. We aimed to validate the diagnostic accuracy of this noninvasive test in an international multicenter study.METHODS: A total of 1924 patients with biopsy-proven nonalcoholic fatty liver disease from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all pa-tients. FibroScan-aspartate aminotransferase score (FAST), an elastography-based test for fibrotic NASH, also was available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with a Nonalcoholic Fatty Liver Disease Activity Score of 4 or higher and fibrosis stage of F2 or higher according to the NASH Clinical Research Network scoring system.RESULTS: The area under the receiver operating characteristic of MACK-3 for fibrotic NASH was 0.791 (95% CI 0.768-0.814). Sensitivity at the previously published MACK-3 threshold of less than 0.135 was 91% and specificity at a greater than 0.549 threshold was 85%. The MACK-3 area under the receiver operating characteristic was not affected by age, sex, diabetes, or body mass index. MACK-3 and FAST results were well correlated (Spearman correlation coefficient, 0.781; P < .001). Except for an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate).CONCLUSIONS: The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials.

引用

页码：3097 / 3106

页数：10