Extrahepatic malignancies in metabolic dysfunction‐associated fatty liver disease: A nationwide cohort study
Background and Aims Metabolic dysfunction‐associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes. Methods This nationwide cohor...
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| Veröffentlicht in: | Liver international 2024-03, Vol.44 (3), p.799-810 |
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| creator | Park, Min Kyung Hur, Moon Haeng Moon, Hye‐Sung Shin, Hyunjae Chung, Sung Won Won, Sungho Lee, Yun Bin Cho, Eun Ju Lee, Jeong‐Hoon Yu, Su Jong Yoon, Jung‐Hwan Kim, Yoon Jun |
| description | Background and Aims
Metabolic dysfunction‐associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes.
Methods
This nationwide cohort study included 9 298 497 patients who participated in a health‐screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non‐MAFLD, diabetes mellitus (DM)‐MAFLD, overweight/obese‐MAFLD and lean‐MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all‐cause and extrahepatic malignancy‐related mortality.
Results
In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow‐up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM‐MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11–1.14; p |
| doi_str_mv | 10.1111/liv.15832 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2915988144</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2915988144</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3532-949a9680693fbe05850bd93806bdf215f6da686fc10371d5b5d6caa0a21de3fe3</originalsourceid><addsrcrecordid>eNp10c1OFTEUB_DGaATRhS9gmrjBxYV-TOe27ghBILmJG3U7OdOeSslMe512xNnxCD6jT0LxAgsTu2lz-ss_J-cQ8pazI17P8RB-HnGlpXhG9nmz1ispJH_-9BZyj7zK-ZoxboziL8me1EIy3eh9Es9-lQmucAslWDrCEL5HiDZgpiHSEQv0aag_bsl-jraEFP_c_oackw1Q0FEPpSy0doATdSEjZPxIT2iEe3oTHFKbrtJUaC6zW16TFx6GjG8e7gPy9dPZl9OL1ebz-eXpyWZlpZJiZRoDptWsNdL3yJRWrHdG1kLvvODKtw5a3XrLmVxzp3rlWgvAQHCH0qM8IIe73O2UfsyYSzeGbHEYIGKacycMV0Zr3jSVvv-HXqd5irW7qqRYM824rurDTtkp5Tyh77ZTGGFaOs66-yV0dQTd3yVU--4hce5HdE_yceoVHO_ATRhw-X9St7n8tou8AwsWkzg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2932708018</pqid></control><display><type>article</type><title>Extrahepatic malignancies in metabolic dysfunction‐associated fatty liver disease: A nationwide cohort study</title><source>Access via Wiley Online Library</source><creator>Park, Min Kyung ; Hur, Moon Haeng ; Moon, Hye‐Sung ; Shin, Hyunjae ; Chung, Sung Won ; Won, Sungho ; Lee, Yun Bin ; Cho, Eun Ju ; Lee, Jeong‐Hoon ; Yu, Su Jong ; Yoon, Jung‐Hwan ; Kim, Yoon Jun</creator><creatorcontrib>Park, Min Kyung ; Hur, Moon Haeng ; Moon, Hye‐Sung ; Shin, Hyunjae ; Chung, Sung Won ; Won, Sungho ; Lee, Yun Bin ; Cho, Eun Ju ; Lee, Jeong‐Hoon ; Yu, Su Jong ; Yoon, Jung‐Hwan ; Kim, Yoon Jun</creatorcontrib><description>Background and Aims
Metabolic dysfunction‐associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes.
Methods
This nationwide cohort study included 9 298 497 patients who participated in a health‐screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non‐MAFLD, diabetes mellitus (DM)‐MAFLD, overweight/obese‐MAFLD and lean‐MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all‐cause and extrahepatic malignancy‐related mortality.
Results
In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow‐up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM‐MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11–1.14; p < .001) and the lean‐MAFLD (aSHR = 1.12; 95% CI = 1.10–1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non‐MAFLD group. However, the overweight/obese‐MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non‐MAFLD group (aSHR = 1.00; 95% CI = .99–1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM‐MAFLD was an independent risk factor for all‐cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40–1.43; p < .001) and extrahepatic malignancy‐related mortality (aHR = 1.20; 95% CI = 1.17–1.23; p < .001).
Conclusion
The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non‐MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.15832</identifier><identifier>PMID: 38230848</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Body weight ; Cirrhosis ; Cohort analysis ; diabetes ; Diabetes mellitus ; Fatty liver ; Health hazards ; lean NAFLD ; Liver ; Liver diseases ; Liver transplantation ; Malignancy ; Metabolic disorders ; Metabolism ; Mortality ; non‐liver cancer ; Overweight ; Risk factors ; Sensitivity analysis ; Subgroups</subject><ispartof>Liver international, 2024-03, Vol.44 (3), p.799-810</ispartof><rights>2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2024 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-949a9680693fbe05850bd93806bdf215f6da686fc10371d5b5d6caa0a21de3fe3</citedby><cites>FETCH-LOGICAL-c3532-949a9680693fbe05850bd93806bdf215f6da686fc10371d5b5d6caa0a21de3fe3</cites><orcidid>0000-0002-9128-3610 ; 0000-0002-0315-2080 ; 0000-0002-3193-9745 ; 0000-0001-7263-6866 ; 0000-0001-9141-7773 ; 0000-0002-2677-3189</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fliv.15832$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fliv.15832$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38230848$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Min Kyung</creatorcontrib><creatorcontrib>Hur, Moon Haeng</creatorcontrib><creatorcontrib>Moon, Hye‐Sung</creatorcontrib><creatorcontrib>Shin, Hyunjae</creatorcontrib><creatorcontrib>Chung, Sung Won</creatorcontrib><creatorcontrib>Won, Sungho</creatorcontrib><creatorcontrib>Lee, Yun Bin</creatorcontrib><creatorcontrib>Cho, Eun Ju</creatorcontrib><creatorcontrib>Lee, Jeong‐Hoon</creatorcontrib><creatorcontrib>Yu, Su Jong</creatorcontrib><creatorcontrib>Yoon, Jung‐Hwan</creatorcontrib><creatorcontrib>Kim, Yoon Jun</creatorcontrib><title>Extrahepatic malignancies in metabolic dysfunction‐associated fatty liver disease: A nationwide cohort study</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>Background and Aims
Metabolic dysfunction‐associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes.
Methods
This nationwide cohort study included 9 298 497 patients who participated in a health‐screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non‐MAFLD, diabetes mellitus (DM)‐MAFLD, overweight/obese‐MAFLD and lean‐MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all‐cause and extrahepatic malignancy‐related mortality.
Results
In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow‐up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM‐MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11–1.14; p < .001) and the lean‐MAFLD (aSHR = 1.12; 95% CI = 1.10–1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non‐MAFLD group. However, the overweight/obese‐MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non‐MAFLD group (aSHR = 1.00; 95% CI = .99–1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM‐MAFLD was an independent risk factor for all‐cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40–1.43; p < .001) and extrahepatic malignancy‐related mortality (aHR = 1.20; 95% CI = 1.17–1.23; p < .001).
Conclusion
The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non‐MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.</description><subject>Body weight</subject><subject>Cirrhosis</subject><subject>Cohort analysis</subject><subject>diabetes</subject><subject>Diabetes mellitus</subject><subject>Fatty liver</subject><subject>Health hazards</subject><subject>lean NAFLD</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Liver transplantation</subject><subject>Malignancy</subject><subject>Metabolic disorders</subject><subject>Metabolism</subject><subject>Mortality</subject><subject>non‐liver cancer</subject><subject>Overweight</subject><subject>Risk factors</subject><subject>Sensitivity analysis</subject><subject>Subgroups</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp10c1OFTEUB_DGaATRhS9gmrjBxYV-TOe27ghBILmJG3U7OdOeSslMe512xNnxCD6jT0LxAgsTu2lz-ss_J-cQ8pazI17P8RB-HnGlpXhG9nmz1ispJH_-9BZyj7zK-ZoxboziL8me1EIy3eh9Es9-lQmucAslWDrCEL5HiDZgpiHSEQv0aag_bsl-jraEFP_c_oackw1Q0FEPpSy0doATdSEjZPxIT2iEe3oTHFKbrtJUaC6zW16TFx6GjG8e7gPy9dPZl9OL1ebz-eXpyWZlpZJiZRoDptWsNdL3yJRWrHdG1kLvvODKtw5a3XrLmVxzp3rlWgvAQHCH0qM8IIe73O2UfsyYSzeGbHEYIGKacycMV0Zr3jSVvv-HXqd5irW7qqRYM824rurDTtkp5Tyh77ZTGGFaOs66-yV0dQTd3yVU--4hce5HdE_yceoVHO_ATRhw-X9St7n8tou8AwsWkzg</recordid><startdate>202403</startdate><enddate>202403</enddate><creator>Park, Min Kyung</creator><creator>Hur, Moon Haeng</creator><creator>Moon, Hye‐Sung</creator><creator>Shin, Hyunjae</creator><creator>Chung, Sung Won</creator><creator>Won, Sungho</creator><creator>Lee, Yun Bin</creator><creator>Cho, Eun Ju</creator><creator>Lee, Jeong‐Hoon</creator><creator>Yu, Su Jong</creator><creator>Yoon, Jung‐Hwan</creator><creator>Kim, Yoon Jun</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9128-3610</orcidid><orcidid>https://orcid.org/0000-0002-0315-2080</orcidid><orcidid>https://orcid.org/0000-0002-3193-9745</orcidid><orcidid>https://orcid.org/0000-0001-7263-6866</orcidid><orcidid>https://orcid.org/0000-0001-9141-7773</orcidid><orcidid>https://orcid.org/0000-0002-2677-3189</orcidid></search><sort><creationdate>202403</creationdate><title>Extrahepatic malignancies in metabolic dysfunction‐associated fatty liver disease: A nationwide cohort study</title><author>Park, Min Kyung ; Hur, Moon Haeng ; Moon, Hye‐Sung ; Shin, Hyunjae ; Chung, Sung Won ; Won, Sungho ; Lee, Yun Bin ; Cho, Eun Ju ; Lee, Jeong‐Hoon ; Yu, Su Jong ; Yoon, Jung‐Hwan ; Kim, Yoon Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-949a9680693fbe05850bd93806bdf215f6da686fc10371d5b5d6caa0a21de3fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Body weight</topic><topic>Cirrhosis</topic><topic>Cohort analysis</topic><topic>diabetes</topic><topic>Diabetes mellitus</topic><topic>Fatty liver</topic><topic>Health hazards</topic><topic>lean NAFLD</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Liver transplantation</topic><topic>Malignancy</topic><topic>Metabolic disorders</topic><topic>Metabolism</topic><topic>Mortality</topic><topic>non‐liver cancer</topic><topic>Overweight</topic><topic>Risk factors</topic><topic>Sensitivity analysis</topic><topic>Subgroups</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Min Kyung</creatorcontrib><creatorcontrib>Hur, Moon Haeng</creatorcontrib><creatorcontrib>Moon, Hye‐Sung</creatorcontrib><creatorcontrib>Shin, Hyunjae</creatorcontrib><creatorcontrib>Chung, Sung Won</creatorcontrib><creatorcontrib>Won, Sungho</creatorcontrib><creatorcontrib>Lee, Yun Bin</creatorcontrib><creatorcontrib>Cho, Eun Ju</creatorcontrib><creatorcontrib>Lee, Jeong‐Hoon</creatorcontrib><creatorcontrib>Yu, Su Jong</creatorcontrib><creatorcontrib>Yoon, Jung‐Hwan</creatorcontrib><creatorcontrib>Kim, Yoon Jun</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Min Kyung</au><au>Hur, Moon Haeng</au><au>Moon, Hye‐Sung</au><au>Shin, Hyunjae</au><au>Chung, Sung Won</au><au>Won, Sungho</au><au>Lee, Yun Bin</au><au>Cho, Eun Ju</au><au>Lee, Jeong‐Hoon</au><au>Yu, Su Jong</au><au>Yoon, Jung‐Hwan</au><au>Kim, Yoon Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extrahepatic malignancies in metabolic dysfunction‐associated fatty liver disease: A nationwide cohort study</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2024-03</date><risdate>2024</risdate><volume>44</volume><issue>3</issue><spage>799</spage><epage>810</epage><pages>799-810</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>Background and Aims
Metabolic dysfunction‐associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes.
Methods
This nationwide cohort study included 9 298 497 patients who participated in a health‐screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non‐MAFLD, diabetes mellitus (DM)‐MAFLD, overweight/obese‐MAFLD and lean‐MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all‐cause and extrahepatic malignancy‐related mortality.
Results
In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow‐up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM‐MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11–1.14; p < .001) and the lean‐MAFLD (aSHR = 1.12; 95% CI = 1.10–1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non‐MAFLD group. However, the overweight/obese‐MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non‐MAFLD group (aSHR = 1.00; 95% CI = .99–1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM‐MAFLD was an independent risk factor for all‐cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40–1.43; p < .001) and extrahepatic malignancy‐related mortality (aHR = 1.20; 95% CI = 1.17–1.23; p < .001).
Conclusion
The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non‐MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38230848</pmid><doi>10.1111/liv.15832</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9128-3610</orcidid><orcidid>https://orcid.org/0000-0002-0315-2080</orcidid><orcidid>https://orcid.org/0000-0002-3193-9745</orcidid><orcidid>https://orcid.org/0000-0001-7263-6866</orcidid><orcidid>https://orcid.org/0000-0001-9141-7773</orcidid><orcidid>https://orcid.org/0000-0002-2677-3189</orcidid></addata></record> |
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| subjects | Body weight Cirrhosis Cohort analysis diabetes Diabetes mellitus Fatty liver Health hazards lean NAFLD Liver Liver diseases Liver transplantation Malignancy Metabolic disorders Metabolism Mortality non‐liver cancer Overweight Risk factors Sensitivity analysis Subgroups |
| title | Extrahepatic malignancies in metabolic dysfunction‐associated fatty liver disease: A nationwide cohort study |
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