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Non-invasive strati...
Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.
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Bianco, Cristina (author)
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- Oveis, Jamialahmadi (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Pelusi, Serena (author)
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Baselli, Guido (author)
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Dongiovanni, Paola (author)
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Zanoni, Irene (author)
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Santoro, Luigi (author)
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Maier, Silvia (author)
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Liguori, Antonio (author)
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Meroni, Marica (author)
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Borroni, Vittorio (author)
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D´Ambrosio, Roberta (author)
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Spagnuolo, Rocco (author)
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Alisi, Anna (author)
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Federico, Alessandro (author)
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Bugianesi, Elisabetta (author)
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Petta, Salvatore (author)
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Miele, Luca (author)
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Vespasiani-Gentilucci, Umberto (author)
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Anstee, Quentin M (author)
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Stickel, Felix (author)
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Hampe, Jochen (author)
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Fischer, Janett (author)
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Berg, Thomas (author)
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Fracanzani, Anna Ludovica (author)
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Soardo, Giorgio (author)
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Reeves, Helen (author)
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Prati, Daniele (author)
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- Romeo, Stefano, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Valenti, Luca (author)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:4, s. 775-782
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https://doi.org/10.1...
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Abstract
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- Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification.We examined at-risk individuals (NAFLD cohort, n=2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n=364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5).In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p=0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p<10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p<0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p<10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ∼90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p<10-5) and without cirrhosis (p<0.05).Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy to detect HCC and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bianco, Cristina
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Oveis, Jamialahm ...
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Pelusi, Serena
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Baselli, Guido
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Dongiovanni, Pao ...
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Zanoni, Irene
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show more...
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Santoro, Luigi
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Maier, Silvia
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Liguori, Antonio
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Meroni, Marica
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Borroni, Vittori ...
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D´Ambrosio, Robe ...
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Spagnuolo, Rocco
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Alisi, Anna
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Federico, Alessa ...
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Bugianesi, Elisa ...
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Petta, Salvatore
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Miele, Luca
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Vespasiani-Genti ...
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Anstee, Quentin ...
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Stickel, Felix
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Hampe, Jochen
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Fischer, Janett
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Berg, Thomas
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Fracanzani, Anna ...
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Soardo, Giorgio
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Reeves, Helen
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Prati, Daniele
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Romeo, Stefano, ...
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Valenti, Luca
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Journal of hepat ...
- By the university
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University of Gothenburg