Diabetes and Risk of Hepatocellular Carcinoma in Cirrhosis Patients with Nonalcoholic Fatty Liver Disease
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. NAFLD is a hepatic manifestation of insulin resistance, the core pathophysiology of diabetes. Multiple clinical studies show that diabetes increases the risk of liver disease progression and cirrhosis development in patients with NAFLD. Diabetes has causal associations with many different cancers, including hepatocellular carcinoma (HCC). More recent studies demonstrate that diabetes increases the risk of HCC in patients with underlying NAFLD cirrhosis, confirming the direct hepatocarcinogenic effect of diabetes among cirrhosis patients. Diabetes promotes hepatocarcinogenesis via the activation of inflammatory cascades producing reactive oxygen species and proinflammatory cytokines, leading to genomic instability, cellular proliferation, and inhibition of apoptosis. Given the global increase in the burden of NAFLD and HCC, high-risk patients such as older diabetic individuals should be carefully monitored for HCC development. Future larger studies should explore whether the effect of diabetes on HCC risk in NAFLD cirrhosis is modifiable by the type of antidiabetic medication and the effectiveness of diabetes control.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. NAFLD is a hepatic manifestation of insulin resistance, the core pathophysiology of diabetes. Multiple clinical studies show that diabetes increases the risk of liver disease progression and cirrhosis development in patients with NAFLD. Diabetes has causal associations with many different cancers, including hepatocellular carcinoma (HCC). More recent studies demonstrate that diabetes increases the risk of HCC in patients with underlying NAFLD cirrhosis, confirming the direct hepatocarcinogenic effect of diabetes among cirrhosis patients. Diabetes promotes hepatocarcinogenesis via the activation of inflammatory cascades producing reactive oxygen species and proinflammatory cytokines, leading to genomic instability, cellular proliferation, and inhibition of apoptosis. Given the global increase in the burden of NAFLD and HCC, high-risk patients such as older diabetic individuals should be carefully monitored for HCC development. Future larger studies should explore whether the effect of diabetes on HCC risk in NAFLD cirrhosis is modifiable by the type of antidiabetic medication and the effectiveness of diabetes control.
참고문헌 (90)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
- Yang JD, "A global view of hepatocellular carcinoma : trends, risk, prevention and management", Nat Rev Gastroenterol Hepatol, 16, pp.589~604 (2019)
- Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)
- Finn RS, "Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma", N Engl J Med, 382, pp.1894~1905 (2020)
- Yang JD, "New advances in the diagnosis and management of hepatocellular carcinoma", BMJ, 371, pp.m3544~ (2020)
- Kew MC, "Aflatoxins as a cause of hepatocellular carcinoma", J Gastrointestin Liver Dis, 22, pp.305~310 (2013)
- Huang DQ, "Global epidemiology of NAFLD-related HCC : trends, predictions, risk factors and prevention", Nat Rev Gastroenterol Hepatol, 18, pp.223~238 (2021)
- Teng PC, "Circulating tumor cells : a step toward precision medicine in hepatocellular carcinoma", J Gastroenterol Hepatol, 37, pp.1179~1190 (2022)
- Fattovich G, "Hepatocellular carcinoma in cirrhosis : incidence and risk factors", Gastroenterology, 127(5 Suppl 1), pp.S35~S50 (2004)
- Singal AG, "HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis : a meta-analysis", J Hepatol, 77, pp.128~139 (2022)
- Noureddin M, "Pathogenesis of NASH : the impact of multiple pathways", Curr Hepatol Rep, 17, pp.350~360 (2018)
- Le MH, "2019 Global NAFLD prevalence : a systematic review and meta-analysis", Clin Gastroenterol Hepatol, 20, pp.2809~2817 (2022)
- Shah PA, "NAFLD-related hepatocellular carcinoma: the growing challenge", Hepatology (2022)[DOI]
- Noureddin M, "Nonalcoholic fatty liver disease, diabetes, obesity, and hepatocellular carcinoma", Clin Liver Dis, 19, pp.361~379 (2015)
- Pelusi S, "Renin-angiotensin system inhibitors, type 2 diabetes and fibrosis progression : an observational study in patients with nonalcoholic fatty liver disease", PLoS One, 11, pp.e0163069~ (2016)
- Noureddin M, "Predicting NAFLD prevalence in the United States using National Health and Nutrition Examination Survey 2017-2018 transient elastography data and application of machine learning", Hepatol Commun, 6, pp.1537~1548 (2022)
- Welzel TM, "Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States", Am J Gastroenterol, 108, pp.1314~1321 (2013)
- Huang DQ, "Changing global epidemiology of liver cancer from 2010 to 2019 : NASH is the fastest growing cause of liver cancer", Cell Metab, 34, pp.969~977 (2022)
- Karim MA, "Clinical characteristics and outcomes of nonalcoholic fatty liver diseaseassociated hepatocellular carcinoma in the United States", Clin Gastroenterol Hepatol (2022)[DOI]
- Dyson J, "Hepatocellular cancer : the impact of obesity, type 2 diabetes and a multidisciplinary team", J Hepatol, 60, pp.110~117 (2014)
- Estes C, "Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030", J Hepatol, 69, pp.896~904 (2018)
- Lee YT, "State-level HCC incidence and association with obesity and physical activity in the United States", Hepatology, 74, pp.1384~1394 (2021)
- Orci LA, "Incidence of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease : a systematic review, meta-analysis, and meta-regression", Clin Gastroenterol Hepatol, 20, pp.283~292 (2022)
- Stine JG, "Systematic review with meta-analysis : risk of hepatocellular carcinoma in nonalcoholic steatohepatitis without cirrhosis compared to other liver diseases", Aliment Pharmacol Ther, 48, pp.696~703 (2018)
- Tan DJH, "Clinical characteristics, surveillance, treatment allocation, and outcomes of nonalcoholic fatty liver disease-related hepatocellular carcinoma : a systematic review and meta-analysis", Lancet Oncol, 23, pp.521~530 (2022)
- El-Serag HB, "Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma", Gastroenterology, 126, pp.460~468 (2004)
- Hassan MM, "Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma", Cancer, 116, pp.1938~1946 (2010)
- El-Serag HB, "The association between diabetes and hepatocellular carcinoma : a systematic review of epidemiologic evidence", Clin Gastroenterol Hepatol, 4, pp.369~380 (2006)
- Kanwal F, "Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in nonalcoholic fatty liver disease", Hepatology, 71, pp.808~819 (2020)
- Targher G, "The complex link between NAFLD and type 2 diabetes mellitus : mechanisms and treatments", Nat Rev Gastroenterol Hepatol, 18, pp.599~612 (2021)
- Veldt BJ, "Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus", Hepatology, 47, pp.1856~1862 (2008)
- Gentile S, "Incidence of altered glucose tolerance in liver cirrhosis", Diabetes Res Clin Pract, 22, pp.37~44 (1993)
- Yang JD, "Diabetes is associated with increased risk of hepatocellular carcinoma in patients with cirrhosis from nonalcoholic fatty liver disease", Hepatology, 71, pp.907~916 (2020)
- Kanwal F, "Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease", Gastroenterology, 155, pp.1828~1837 (2018)
- Singh MK, "Diabetes and hepatocellular carcinoma : a pathophysiological link and pharmacological management", Biomed Pharmacother, 106, pp.991~1002 (2018)
- Moon WS, "Overexpression of VEGF and angiopoietin 2 : a key to high vascularity of hepatocellular carcinoma?", Mod Pathol, 16, pp.552~557 (2003)
- Popova EA, "Non-enzymatic glycosylation and deglycating enzymes", Biotechnol Biotechnol Equip, 24, pp.1928~1935 (2014)
- Assi M, "The differential role of reactive oxygen species in early and late stages of cancer", Am J Physiol Regul Integr Comp Physiol, 313, pp.R646~R653 (2017)
- Peverill W, "Evolving concepts in the pathogenesis of NASH : beyond steatosis and inflammation", Int J Mol Sci, 15, pp.8591~8638 (2014)
- Wang TN, "Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss", Kaohsiung J Med Sci, 29, pp.436~443 (2013)
- Coppack SW, "Adipose tissue changes in obesity", Biochem Soc Trans, 33(Pt 5), pp.1049~1052 (2005)
- Cerf ME, "Beta cell dysfunction and insulin resistance", Front Endocrinol(Lausanne), 4, pp.37~ (2013)
- Allaire M, "Type 2 diabetes-associated hepatocellular carcinoma: a molecular profile", Clin Liver Dis(Hoboken), 8, pp.53~58 (2016)
- Yadav A, "Correlation of adiponectin and leptin with insulin resistance : a pilot study in healthy north Indian population", Indian J Clin Biochem, 26, pp.193~196 (2011)
- Finucane FM, "Correlation of the leptin : adiponectin ratio with measures of insulin resistance in non-diabetic individuals", Diabetologia, 52, pp.2345~2349 (2009)
- Tovar V, "IGF activation in a molecular subclass of hepatocellular carcinoma and preclinical efficacy of IGF-1R blockage", J Hepatol, 52, pp.550~559 (2010)
- Chettouh H, "Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma", Liver Int, 35, pp.2203~2217 (2015)
- Michelotti GA, "NAFLD, NASH and liver cancer", Nat Rev Gastroenterol Hepatol, 10, pp.656~665 (2013)
- Fujii M, "A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma", Med Mol Morphol, 46, pp.141~152 (2013)
- Flemming JA, "Risk prediction of hepatocellular carcinoma in patients with cirrhosis : the ADRESS-HCC risk model", Cancer, 120, pp.3485~3493 (2014)
- Sharma SA, "Toronto HCC risk index : a validated scoring system to predict 10-year risk of HCC in patients with cirrhosis", J Hepatol, 68, pp.P92~P99 (2018)
- Lambrecht J, "The APAC score : a novel and highly performant serological tool for early diagnosis of hepatocellular carcinoma in patients with liver cirrhosis", J Clin Med, 10, pp.3392~ (2021)
- Fujiwara N, "Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease", Sci Transl Med, 14, pp.eabo4474~ (2022)
- Weston SR, "Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease", Hepatology, 41, pp.372~379 (2005)
- Ford ES, "Prevalence of the metabolic syndrome among US adults : findings from the third National Health and Nutrition Examination Survey", JAMA, 287, pp.356~359 (2002)
- Bianco C, "Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores", J Hepatol, 74, pp.775~782 (2021)
- Gellert-Kristensen H, "Combined effect of PNPLA3, TM6SF2, and HSD17B13 variants on risk of cirrhosis and hepatocellular carcinoma in the general population", Hepatology, 72, pp.845~856 (2020)
- Pelusi S, "Rare pathogenic variants predispose to hepatocellular carcinoma in nonalcoholic fatty liver disease", Sci Rep, 9, pp.3682~ (2019)
- Donati B, "MBOAT7 rs641738variant and hepatocellular carcinoma in non-cirrhotic individuals", Sci Rep, 7, pp.4492~ (2017)
- Yang JD, "GALAD score for hepatocellular carcinoma detection in comparison with liver ultrasound and proposal of GALADUS score", Cancer Epidemiol Biomarkers Prev, 28, pp.531~538 (2019)
- Younes R, "Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease", J Hepatol, 75, pp.786~794 (2021)
- Wu X, "Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma", Int J Biol Sci, 16, pp.1551~1562 (2020)
- Ahn JC, "Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma", Hepatology, 73, pp.422~436 (2021)
- Lee YT, "The role of extracellular vesicles in disease progression and detection of hepatocellular carcinoma", Cancers(Basel), 13, pp.3076~ (2021)
- Kalinich M, "An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma", Proc Natl Acad Sci U S A, 114, pp.1123~1128 (2017)
- Sun N, "Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring", Nat Commun, 11, pp.4489~ (2020)
- Polesel J, "The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma", Ann Oncol, 20, pp.353~357 (2009)
- Regimbeau JM, "Obesity and diabetes as a risk factor for hepatocellular carcinoma", Liver Transpl, 10(2 Suppl 1), pp.S69~S73 (2004)
- Caldwell SH, "Obesity and hepatocellular carcinoma", Gastroenterology, 127(5Suppl 1), pp.S97~S103 (2004)
- Abdel-Rahman O, "Cigarette smoking as a risk factor for the development of and mortality from hepatocellular carcinoma : an updated systematic review of 81 epidemiological studies", J Evid Based Med, 10, pp.245~254 (2017)
- Amable G, "Metformin inhibits β-catenin phosphorylation on Ser-552 through an AMPK", PI3K, Int J Biochem Cell Biol, pp.2019, 112[DOI]
- Loubière C, "Metformin-induced energy deficiency leads to the inhibition of lipogenesis in prostate cancer cells", Oncotarget, 6, pp.15652~15661 (2015)
- Zhao B, "Anticancer mechanisms of metformin : a review of the current evidence", Life Sci, 254, pp.117717~ (2020)
- Golay A, "Metformin and body weight", Int J Obes(Lond), 32, pp.61~72 (2008)
- Chen HP, "Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner : population-based and in vitro studies", Gut, 62, pp.606~615 (2013)
- Singh S, "Antidiabetic medications and the risk of hepatocellular cancer : a systematic review and meta-analysis", Am J Gastroenterol, 108, pp.881~891 (2013)
- Kramer JR, "Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease", Hepatology, 75, pp.1420~1428 (2022)
- Cunha V, "Metformin in the prevention of hepatocellular carcinoma in diabetic patients : a systematic review", Ann Hepatol, 19, pp.232~237 (2020)
- Tseng CH, "Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes", Liver Int, 38, pp.2018~2027 (2018)
- McGuire DK, "Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes : a meta-analysis", JAMA Cardiol, 6, pp.148~158 (2021)
- Zelniker TA, "SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes : a systematic review and meta-analysis of cardiovascular outcome trials", Lancet, 393, pp.31~39 (2019)
- Arvanitakis K, "The effects of sodium-glucose cotransporter 2 inhibitors on hepatocellular carcinoma : from molecular mechanisms to potential clinical implications", Pharmacol Res, 181, pp.106261~ (2022)
- Luo J, "Canagliflozin modulates hypoxia-induced metastasis, angiogenesis and glycolysis by decreasing HIF-1α protein synthesis via AKT", mTOR pathway, 2021, pp.22, 13336~
- Benedetti R, "Effects of novel SGLT2 inhibitors on cancer incidence in hyperglycemic patients : a meta-analysis of randomized clinical trials", Pharmacol Res, 175, pp.106039~ (2022)
- El-Serag HB, "Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes", Gastroenterology, 136, pp.1601~1608 (2009)
- Singh S, "Statins are associated with a reduced risk of hepatocellular cancer : a systematic review and meta-analysis", Gastroenterology, 144, pp.323~332 (2013)
- Zou B, "Statin use and reduced hepatocellular carcinoma risk in patients with nonalcoholic fatty liver disease", Clin Gastroenterol Hepatol (2022)[DOI]
- Chen H, "Hepatic cyclooxygenase-2overexpression induced spontaneous hepatocellular carcinoma formation in mice", Oncogene, 36, pp.4415~4426 (2017)
- Kern MA, "Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells", Hepatology, 36(4 Pt 1), pp.885~894 (2002)
- Simon TG, "Association between aspirin use and risk of hepatocellular carcinoma", JAMA Oncol, 4, pp.1683~1690 (2018)
