Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly

Abstract

Limited data exist regarding metabolic risk factors for deaths from hepatocellular carcinoma (HCC) in aging individuals. We investigated the association between diabetes, dyslipidemia, and HCC mortality in those aged 40 years or more (middle-aged and elderly). In this prospective cohort study based on nationwide health screening units, we consecutively followed middle-aged and elderly participants who had no chronic hepatitis B or C virus infection and received health screening from January 1 1998 to December 31 2008. There were 235 deaths from HCC among 50,080 individuals, ascertained by validated death certificates and the national death registry. Diabetes (adjusted hazard ratio [HR], 3.38; 95% confidence interval [CI], 2.35 to 4.86) was positively associated with deaths from HCC. However, hypertriglyceridemia (HR, 0.38; 95% CI, 0.26 to 0.55) and hypercholesterolemia (HR, 0.50; 95% CI, 0.37 to 0.67) were inversely associated with HCC mortality. The above significant associations remained in the lag time analyses, applied to check for reverse causation. Metabolic syndrome, as defined by the American Heart Association / National Heart Lung Blood Institute criteria (HR, 0.63; 95% CI, 0.46 to 0.86) or by the International Diabetes Federation criteria (HR, 0.62; 95% CI, 0.43 to 0.89), was inversely associated with deaths from HCC, especially in men. Conclusion: Middle-aged and elderly individuals, once having diabetes, deserve HCC surveillance to reduce HCC mortality. More research is needed to elucidate why having baseline dyslipidemia relates to lower future HCC mortality. (HEPATOLOGY 2014;59:2207-2215

Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U.S. Adults

“…Few studies have examined the association between WC and risk of liver cancer (12–14) and the results are mixed. A large European cohort study identified 177 liver cancers and reported HRs for the associations of WC (per 5 cm) and liver cancer risk that were similar with (HR: 1.29) and without (HR: 1.25) control for BMI (14).…”

“…To date, U.S.-based prospective studies on this topic are especially rare: a two-fold higher risk of HCC was reported when comparing obese (≥30 kg/m 2 ) to normal BMI (18.5<25 kg/m 2 ) in a cohort study of 2,126 cirrhosis patients (11). The few prospective studies that examined the association between waist circumference (WC), an indicator of central adiposity, and liver cancer risk are somewhat conflicting, likely due to small sample sizes, but generally suggest higher risk with increasing WC (12–14). These observations are supported by findings that general and central adiposity are associated with higher risks of nonalcoholic fatty liver disease (NAFLD) and the more severe nonalcoholic steatohepatitis (NASH), both of which are major risk factors for liver cancer (15).…”

“…Several prospective studies and meta-analyses support a higher risk of liver cancer incidence and mortality among persons with diabetes (8, 12, 16–21), but many early studies were from administrative datasets that were unable to adjust for important confounders, including BMI, or had short follow-up times that may have been prone to biases. Prospectively collected data with sufficiently long follow-up time are important in this context because the clinical diagnosis of liver cancer and diabetes may coincide (i.e., reverse causation) (22).…”

Metabolic disorders across hepatocellular carcinoma in Italy

“…However, in concert with the recent epidemic of obesity and metabolic syndrome in developed countries, the incidence and prevalence of non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) have also increased, and today they represent rapidly growing causes of end‐stage liver disease and HCC . Moreover, regardless of the aetiology of liver disease, metabolic disorders, such as obesity and diabetes, contribute to hepato‐cancerogenesis . Indeed, there are well established pathophysiological mechanisms linking obesity, diabetes and HCC .…”

Hyperglycemia and chronic liver diseases on risk of hepatocellular carcinoma in Chinese patients with type 2 diabetes––National cohort of Taiwan Diabetes Study

“…The International Diabetes Federation proposed that the causes for increased diabetes prevalence are population ageing and unhealthy lifestyle behaviors, including physical inactivity, smoking, alcohol consumption and an unhealthy diet. Recent epidemiological findings of cohort and case‐control studies have indicated a link between Type 2 diabetes and cancer in several organs, particularly the liver . Type 2 diabetes mellitus and many types of cancer share common risk factors such as smoking, alcohol consumption, obesity, physical inactivity, a high calorie intake and particularly saturated fat intake .…”