Doença hepática gordurosa não-alcoólica e neoplasias extra-hepáticas: uma revisão narrativa

REZENDE, Achiles Queiroz Monteiro de; CAZZO, Everton

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Sumário

ORIGINAL ARTICLE/HEPATOLOGY • Arq. Gastroenterol. 61 • 2024 • https://doi.org/10.1590/S0004-2803.24612023-027 copiar

Doença hepática gordurosa não-alcoólica e neoplasias extra-hepáticas: uma revisão narrativa

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

Contexto:

Recentemente, associações significativas entre a doença hepática gordurosna não-alcoólica (DHGNA) e neoplasias extra-hepáticas têm sido descritas.

Objetivo:

Realizar uma revisão abrangente acerca das evidências atuais na literatura sobre a associação entre DHGNA e neoplasias extra-hepáticas.

Métodos:

Uma revisão narrativa de literatura foi realizada através da busca on-line pelos descritores “fígado gorduroso” e “câncer” em MEDLINE (através do PubMed) e LILACS (através da BVS). Estudos originais que descreveram o impacto da DHGNA em diferentes tipos de neoplasias malignas extra-hepáticas foram incluídos.

Resultados:

Após análise criteriosa, nove estudos prospectivos de coorte, um coorte histórica, três estudos de caso-controle, e três estudos transversais foram selecionados.

Conclusão:

Existem evidências consistentes a respeito da associação entre DHGNA e a carcinogênese extra-hepática, especialmente em relação aos cânceres de cólon e reto, estômago, pâncreas, mama, próstata e bexiga.

Palavras-Chave:
Hepatopatia gordurosa não-alcoólica; obesidade; câncer; carcinogênese; fígado gorduroso.

Study	Year of publication	Country of origin	N	Type of cancer	Methodology	Mean follow-up (years)	Level of evidence	NAFLD Diagnosis	Main findings
Hamaguchi et al.⁵5. Hamaguchi M, Hashimoto Y, Obora A, Kojima T, Fukui M. Non-alcoholic fatty liver disease with obesity as an independent predictor for incident gastric and colorectal cancer: a population-based longitudinal study. BMJ Open Gastroenterol. 2019;6:e000295.	2019	Japan	27,944	Gastric and colorectal	Single-center prospective	6.5	2b	Ultrasound scan	NAFLD with obesity was a risk factor for both incident gastric cancer and colorectal cancer
Nseir et al.¹⁴14. Nseir W, Abu-Rahmeh Z, Tsipis A, Mograbi J, Mahamid M. Relationship between Non-Alcoholic Fatty Liver Disease and Breast Cancer. Isr Med Assoc J. 2017;19:242-5.	2017	Israel	133	Breast	Single-center cross-sectional	NA	3b	Computed tomography	Multivariate analysis showed NAFLD to be associated with breast cancer
Kim et al.¹⁰10. Kim GA, Lee HC, Choe J, Kim MJ, Lee MJ, Chang HS, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate. J Hepatol. 2017;S0168-8278:32294-8.	2017	South Korea	25,947	Several	Single-center prospective	7.5	2b	Ultrasound scan	NAFLD was associated with the development of hepatocellular carcinoma, colorectal cancer in males, and breast cancer in females
Chang et al.³⁶36. Chang CF, Tseng YC, Huang HH, Shih YL, Hsieh TY, Lin HH. Exploring the relationship between nonalcoholic fatty liver disease and pancreatic cancer by computed tomographic survey. Intern Emerg Med. 2018;13:191-7.	2018	Taiwan	557	Pancreatic	Single-center cross-sectional	NA	2c	Computed tomography	NAFLD is positively correlated with pancreatic cancer, a result suggesting that NAFLD may increase the incidence and risk of pancreatic cancer. Patients with pancreatic cancer and NAFLD have poorer overall survival than patients without NAFLD
Hwang et al.⁴¹41. Hwang YC, Ahn HY, Park SW, Park CY. Nonalcoholic Fatty Liver Disease Associates With Increased Overall Mortality and Death From Cancer, Cardiovascular Disease, and Liver Disease in Women but Not Men. Clin Gastroenterol Hepatol. 2018;16:1131-7.e5.	2018	South Korea	318,224	Mortality cause by any cancer	Single-cente-r prospective	5.7	2b	Ultrasound scan	NAFLD was associated with increased overall mortality from cancer
Choi et al.¹⁶16. Choi YJ, Lee DH, Han KD, Yoon H, Shin CM, Park YS, et al. Is nonalcoholic fatty liver disease associated with the development of prostate cancer? A nationwide study with 10,516,985 Korean men. PLoS One. 2019;13:e0201308.	2018	South Korea	10,516,985	Prostate	Nationwide population-based prospective	5.33	2b	Fatty liver index	NAFLD may help identify high-risk individuals for developing prostate cancer, even in the absence of obesity or metabolic syndrome
Kwak et al.¹⁵15. Kwak MS, Yim JY, Yi A, Chung GE, Yang JI, Kim D, et al. Nonalcoholic fatty liver disease is associated with breast cancer in nonobese women. Dig Liver Dis. 2019;51:1030-5.	2019	South Korea	540	Breast	Single-center case-control	NA	3b	Ultrasound scan	NAFLD was significantly associated with breast cancer independent of traditional risk factors in women without obesity
Park et al.¹³13. Park JH, Choi IS, Han KD, Park H, Kim KH, Kim JS. Association Between Fatty Liver Index and Risk of Breast Cancer: A Nationwide Population-Based Study. Clin Breast Cancer. 2020;20:e450-e457.	2020	South Korea	7,046,153	Breast	Nationwide population-based prospective cohort	7.0	2b	Fatty liver index	High FLI values significantly associated with increased breast cancer risk in postmenopausal women, but not in premenopausal women
Choi et al.⁴²42. Choi YJ, Lee DH, Han KD. Association between high fatty liver index and development of colorectal cancer: a nationwide cohort study with 21,592,374 Korean. Korean J Intern Med. 2020;35:1354-63.	2020	South Korea	21,592,374	Colorectal	Nationwide population-based prospective	5.3	2b	Fatty liver index	Multivariate logistic regression analysis demonstrated an independent association between NAFLD and colorectal cancer after adjusting for other confounders. In subgroup analyses, fatty liver index ≥60 was associated with CRC regardless of body mass index, but the association was more prominent in lean persons
Chiang et al.¹⁷17. Chiang CL, Huang HH, Huang TY, Shih YL, Hsieh TY, Lin HH. Nonalcoholic Fatty Liver Disease Associated With Bladder Cancer. Am J Med Sci. 2020;360:161-5.	2020	Taiwan	517	Bladder	Single-center case-control	NA	3b	Computed tomography	NAFLD was positively associated with bladder cancer and was a poor prognostic factor of bladder cancer
Lee et al.⁴³43. Lee JM, Park YM, Yun JS, Ahn YB, Lee KM, Kim DB, et al. The association between nonalcoholic fatty liver disease and esophageal, stomach, or colorectal cancer: National population-based cohort study. PLoS One. 2020;15:e0226351.	2020	South Korea	8,120,674	Esophageal, gastric, and colorectal	Nationwide population-based cross-sectional	NA	2c	Fatty liver index	FLI ≥60 was significantly associated with the development of esophageal, stomach, and colon cancer after multivariable adjustment
Simon et al.¹²12. Simon TG, Roelstraete B, Sharma R, Khalili H, Hagström H, Ludvigsson JF. Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study. Hepatology. 2021;74:2410-23.	2021	Sweden	8,892	Several	Nationwide population-based prospective cohort	15.5	2b	Liver biopsy	NAFLD was associated with highly increased rates of HCC and modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma, but no other cancers
Yamamoto et al.⁴⁴44. Yamamoto K, Ikeya T, Okuyama S, Fukuda K, Kobayashi D. The association between non-alcoholic fatty liver disease (with or without metabolic syndrome) and extra-hepatic cancer development. J Gastroenterol Hepatol. 2021;36:1971-8.	2021	Japan	30,172	Several	Single-center retrospective	14.0	2b	Ultrasound scan	NAFLD associated with the development of gastrointestinal malignancies, especially in the stomach and small intestine
Rezende et al.⁸8. Rezende AQM, Gestic MA, Utrini MP, Chaim FDM, Saito HPA, Chaim E, et al. Is there a link between non-alcoholic fatty liver disease aspects and pancreatic cancer? Results of a case-matched study. Rev Col Bras Cir. 2021;48:e20202913.	2021	Brazil	56	Pancreatic	Single-center case-control	NA	3b	Liver Biopsy	Significant associations were identified between histopathological aspects of NAFLD (microvesicular steatosis, hepatocellular ballooning, fibrosis, and steatohepatitis) and pancreatic cancer
Lee et al.⁴⁵45. Lee H, Lee HW, Kim SU, Chang Kim H. Metabolic Dysfunction-Associated Fatty Liver Disease Increases Colon Cancer Risk: A Nationwide Cohort Study. Clin Transl Gastroenterol. 2022;13:e00435.	2022	South Korea	8,933,017	Colorectal	Nationwide population-based prospective	10.1	2b	Fatty liver index	NAFLD was associated with a higher risk of CRC development
Park et al.⁴⁶46. Park JH, Hong JY, Han K, Kang W, Park JK. Increased risk of pancreatic cancer in individuals with non-alcoholic fatty liver disease. Sci Rep. 2022;12:10681.	2022	South Korea	8,120,674	Pancreatic	Nationwide population-based prospective	7.2	2b	Fatty liver index	NAFLD was independently associated with an increased risk of pancreatic cancer, regardless of obesity

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[1] Corresponding author: Everton Cazzo. notrevezzo@yahoo.com.br