Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study

被引：78

作者：

Serra-Burriel, Miquel ^{[1
]}

Juanola, Adria ^{[2
,4
,5
]}

Serra-Burriel, Feliu ^{[6
]}

Thiele, Maja ^{[7
]}

Graupera, Isabel ^{[2
,3
,4
,5
]}

Pose, Elisa ^{[4
,5
]}

Pera, Guillem

Grgurevic, Ivica ^{[10
,11
]}

Caballeria, Llorenc ^{[12
]}

Piano, Salvatore ^{[13
]}

van Kleef, Laurens ^{[14
]}

Reichert, Mathias ^{[16
]}

Roulot, Dominique ^{[17
]}

Pericas, Juan M. ^{[18
,19
]}

Schattenberg, Joern M. ^{[20
]}

Tsochatztis, Emmanuel A. ^{[21
]}

Guha, Indra Neil ^{[22
,23
]}

Garcia-Retortillo, Montserrat ^{[24
]}

Hernandez, Rosario ^{[25
]}

Hoyo, Jordi ^{[25
]}

Fuentes, Matilde ^{[25
]}

Exposito, Carmen ^{[26
]}

Martinez, Alba ^{[26
]}

Such, Patricia ^{[27
,28
]}

Madir, Anita ^{[10
,11
]}

Detlefsen, Sonke ^{[8
,9
]}

Tonon, Marta ^{[13
]}

Martini, Andrea ^{[13
]}

Ma, Ann T.

Pich, Judith ^{[29
]}

Bonfill, Eva ^{[29
]}

Juan, Marta ^{[29
]}

Soria, Anna ^{[2
,5
]}

Carol, Marta ^{[2
,3
,4
,5
]}

Gratacos-Gines, Jordi ^{[2
,4
,5
]}

Morillas, Rosa M. ^{[30
]}

Toran, Pere ^{[26
]}

Navarrete, J. M. ^{[27
,28
]}

Torrejon, Antoni ^{[27
,28
]}

Fournier, Celine ^{[31
]}

Llorca, Anne ^{[31
]}

Arslanow, Anita ^{[2
,4
]}

de Koning, Harry J. ^{[15
]}

Cucchietti, Fernando ^{[6
]}

Manns, Michael ^{[32
]}

Newsome, Phillip N. ^{[33
,34
]}

Hernaez, Ruben ^{[35
,36
,37
]}

Allen, Alina ^{[38
]}

Angeli, Paolo ^{[13
]}

de Knegt, Robert J. ^{[14
]}

机构：

[1] Univ Zurich, Epidemiol Stat & Prevent Inst, Zurich, Switzerland

[2] Univ Barcelona, Hosp Clin, Liver Unit, Barcelona, Spain

[3] Univ Barcelona, Fac Med & Hlth Sci, Barcelona, Spain

[4] Inst Invest Biomed August Pi I Sunyer, Barcelona, Catalonia, Spain

[5] Ctr Invest Red Enfermedades Hepat & Diges, Barcelona, Spain

[6] Barcelona Super Comp Ctr, Barcelona, Spain

[7] Univ Southern Denmark Odense, Inst Clin Res, Dept Gastroenterol & Hepatol, Ctr Liver Res, Odense, Denmark

[8] Univ Southern Denmark Odense, Odense Univ Hosp, Dept Pathol, Inst Clin Res, Odense, Denmark

[9] Univ Southern Denmark Odense, Inst Clin Res, Odense, Denmark

[10] Univ Zagreb, Sch Med, Univ Hosp Dubrava, Dept Gastroenterol Hepatol & Clin Nutr, Zagreb, Croatia

[11] Fac Pharm & Biochem, Zagreb, Croatia

[12] ICS Inst Catala Salut, Fundacio Inst Univ Recerca Atencio Primaria Salut, Metropolitana Nord, Unitat Suport Recerca Metropolitana Nord,IDIAP Jo, Barcelona, Spain

[13] Univ Padua, Dept Med, Unit Internal Med & Hepatol, Padua, Italy

[14] Erasmus MC, Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands

[15] Erasmus MC, Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands

[16] Saarland Univ, Med Ctr, Dept Med 2, Homburg, Germany

[17] Univ Paris 13, Hop Avicenne, AP HP, Unite Hepatol, Bobigny, France

[18] Vall dHebron Barcelona Hosp Campus, Vall dHebron Inst Recerca, Hosp Univ Vall dHebron, Dept Internal Med,Liver Unit, Barcelona, Spain

[19] Univ Autonoma Barcelona, Barcelona, Spain

[20] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med 1, Mainz, Germany

[21] UCL, Royal Free Hosp, UCL Inst Liver & Digest Hlth, London, England

[22] Nottingham Univ Hosp NHS Trust, Nottingham Biomed Res Ctr, Nottingham, England

[23] Univ Nottingham, Nottingham, England

[24] Hosp Mar, IMIM, Dept Med, Gastroenterol Dept,Liver Sect, Barcelona, Spain

[25] Inst Catala Salut, BCN, Ambit Atencio Primaria, Barcelona, Spain

[26] Inst Univ Invest Atencio Primaria Jordi Gol, Unitat Suport Recerca Metropolitana Nord, Barcelona, Spain

[27] CUPRA, Hlth Safety & Emergencies SEAT, Martorell, Spain

[28] Volkswagen Grp Co Spain, Martorell, Spain

[29] Hosp Clin Barcelona, Clin Trial Unit, Barcelona, Spain

[30] Hosp Germans Trias i Pujol, IGTP, Liver Unit, Badalona, Spain

[31] Echosens, Paris, France

[32] Hannover Med Sch MHH, Hlth Sci, Hannover, Germany

[33] Univ Hosp Birmingham NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, Birmingham, W Midlands, England

[34] Univ Birmingham, Birmingham, W Midlands, England

[35] Michael E DeBakey VA Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Houston, TX USA

[36] Michael E DeBakey VA Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Houston, TX USA

[37] Baylor Coll Med, Dept Med, Div Gastroenterol & Hepatol, Houston, TX 77030 USA

[38] Mayo Clin, Coll Med & Sci, Div Gastroenterol & Hepatol, Rochester, MN USA

[39] Oslo Univ Hosp, Dept Transplantat Med, Sect Gastroenterol, Oslo, Norway

[40] Oslo Univ Hosp, Inst Clin Med, Oslo, Norway

[41] Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway

[42] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China

[43] Univ Paris, Hop Beaujon, Assistance Publ Hop Paris, Clichy,Dept Hepatol, Clichy, France

[44] Saarland Univ, Inst Occupat Med & Publ Hlth, Homburg, Germany

[45] Hannover Med Sch, Hannover, Germany

来源：

LANCET | 2023年 / 402卷 / 10406期

关键词：

DISEASE; PREVALENCE; FIBROSIS; ADULTS;

D O I：

10.1016/S0140-6736(23)01174-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. Methods We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). Findings We included 14 726 participants: 6357 (43 center dot 2%) in the derivation cohort, 4370 (29 center dot 7%) in the first external validation cohort, and 3999 (27 center dot 2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0 center dot 83 [95% CI [0 center dot 78-0 center dot 89]) versus the fibrosis-4 index (FIB-4; 0 center dot 68 [0 center dot 61-0 center dot 75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liverrelated mortality was 0 center dot 90 (0 center dot 88-0 center dot 91) versus 0.84 (0 center dot 82-0 center dot 86) for FIB-4. Interpretation The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care.

引用

页码：988 / 996

页数：9

共 30 条

[1] Simple Noninvasive Systems Predict Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease [J].

Angulo, Paul ;

Bugianesi, Elisabetta ;

Bjornsson, Einar S. ;

Charatcharoenwitthaya, Phunchai ;

Mills, Peter R. ;

Barrera, Francisco ;

Haflidadottir, Svanhildur ;

Day, Christopher P. ;

George, Jacob .

GASTROENTEROLOGY, 2013, 145 (04) :782-+

[2] Nichtinvasive Früherkennung von Lebererkrankungen im Rahmen der betrieblichen GesundheitsförderungNoninvasive early detection of liver diseases as part of occupational health check-ups [J].

A. Arslanow ;

C. Baum ;

F. Lammert ;

C. S. Stokes .

Zentralblatt für Arbeitsmedizin, Arbeitsschutz und Ergonomie, 2017, 67 (4) :201-210

[3] Burden of liver diseases in the world [J].

Asrani, Sumeet K. ;

Devarbhavi, Harshad ;

Eaton, John ;

Kamath, Patrick S. .

JOURNAL OF HEPATOLOGY, 2019, 70 (01) :151-171

[4] Cost-effectiveness of alcohol use treatments in patients with alcohol-related cirrhosis [J].

Avancena, Anton L. V. ;

Miller, Nicholas ;

Uttal, Sarah E. ;

Hutton, David W. ;

Mellinger, Jessica L. .

JOURNAL OF HEPATOLOGY, 2021, 74 (06) :1286-1294

[5] Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals [J].

Bazerbachi, Fateh ;

Haffar, Samir ;

Wang, Zhen ;

Cabezas, Joaquin ;

Teresa Arias-Loste, Maria ;

Crespo, Javier ;

Darwish-Murad, Sarwa ;

Ikram, M. Arfan ;

Olynyk, John K. ;

Gan, Eng ;

Petta, Salvatore ;

Berzuini, Alessandra ;

Prati, Daniele ;

de Ledinghen, Victor ;

Wong, Vincent W. ;

Del Poggio, Paolo ;

Chavez-Tapia, Norberto C. ;

Chen, Yong-Peng ;

Cheng, Pin-Nan ;

Yuen, Man-Fung ;

Das, Kausik ;

Chowdhury, Abhijit ;

Caballeria, Llorenc ;

Fabrellas, Nuria ;

Gines, Pere ;

Kumar, Manoj ;

Sarin, Shiv Kumar ;

Conti, Fabio ;

Andreone, Pietro ;

Sirli, Roxana ;

Cortez-Pinto, Helena ;

Carvalhana, Sofia ;

Sugihara, Takaaki ;

Kim, Seung Up ;

Parikh, Pathik ;

Chayama, Kazuaki ;

Corpechot, Christophe ;

Kim, Kang Mo ;

Papatheodoridis, George ;

Alsebaey, Ayman ;

Kamath, Patrick S. ;

Murad, M. Hassan ;

Watt, Kymberly D. .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2019, 17 (01) :54-+

[6] EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis-2021 update [J].

Berzigotti, Annalisa ;

Tsochatzis, Emmanouil ;

Boursier, Jerome ;

Castera, Laurent ;

Cazzagon, Nora ;

Friedrich-Rust, Mireen ;

Petta, Salvatore ;

Thiele, Maja .

JOURNAL OF HEPATOLOGY, 2021, 75 (03) :659-689

[7] High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study [J].

Caballeria, Llorenc ;

Pera, Guillem ;

Arteaga, Ingrid ;

Rodriguez, Lluis ;

Aluma, Alba ;

Morillas, Rosa Ma ;

de la Ossa, Napoleon ;

Diaz, Alba ;

Exposito, Carmen ;

Miranda, Dolores ;

Sanchez, Carmen ;

Prats, Rosa M. A. ;

Urquizu, Marta ;

Salgado, Angels ;

Alemany, Magda ;

Martinez, Alba ;

Majeed, Irfan ;

Fabrellas, Nuria ;

Graupera, Isabel ;

Planas, Ramon ;

Ojanguren, Isabel ;

Serra, Miquel ;

Toran, Pere ;

Caballeria, Juan ;

Gines, Pere .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2018, 16 (07) :1138-+

[8] Enhanced recursive feature elimination [J].

Chen, Xue-Wen ;

Jeong, Jong Cheol .

ICMLA 2007: SIXTH INTERNATIONAL CONFERENCE ON MACHINE LEARNING AND APPLICATIONS, PROCEEDINGS, 2007, :429-435

[9]

Culp M, 2006, J STAT SOFTW, V17, P1

[10] Baveno VII - Renewing consensus in portal hypertension [J].

de Franchis, Roberto ;

Bosch, Jaime ;

Garcia-Tsao, Guadalupe ;

Reiberger, Thomas ;

Ripoll, Cristina .

JOURNAL OF HEPATOLOGY, 2022, 76 (04) :959-974

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