Diabetes and Hepatocellular Carcinoma: What Role Does Diabetes Have in the Presence of Other Known Risk Factors?

Abstract

Known risk factors for hepatocellular carcinoma (HCC) include hepatitis C, hepatitis B, and alcoholic liver disease. Several studies have examined diabetes as a risk factor for HCC because of its association with fatty liver disease and nonalcoholic steatohepatitis. The current study by Tung et al. found that neither diabetes nor overweight was a risk factor for HCC. Results were consistent using both a cross-sectional and a case -control study approach. Findings from this study suggest that diabetes and overweight alone are not adequate to increase the risk of HCC in the absence of concomitant viral hepatitis or liver disease. Am J Gastroenterol 2010; 105:632 -634; doi: 10.1038/ajg.2009 Th e incidence of hepatocellular carcinoma (HCC) in the United States has more than doubled over the past two decades ( 1 ). Primary known risk factors for HCC are hepatitis C virus (HCV), hepatitis B virus (HBV), and alcoholic liver disease ( 2,3 ). Yet previous studies have reported the absence of these risk factors in up to 50 % of HCC cases ( 4 ). Other potential risk factors for HCC include diabetes and obesity as measured by body mass index (BMI). Th e proposed mechanism of HCC development for diabetes and obesity is through the development of fatty liver disease and non-alcoholic steatohepatitis (NASH). Th e pathogenesis of NASH involves insulin resistance, which is associated with both obesity and diabetes ( 5 ). Several studies have examined the association between HCC and diabetes. Earlier studies reported no association between diabetes and HCC, while more recent studies have identifi ed diabetes as a risk factor for HCC ( 6 -15 ). A study conducted among a large cohort of Veterans found that the incidence of HCC was increased more than twofold among patients with diabetes, and that the risk of developing HCC among patients with diabetes was 2.2 times greater than in patients without diabetes ( 9 ). Another population-based case -control study using the Surveillance, Epidemiology and End Results Medicare database reported an odds ratio of 2.87 (95 % confi dence interval (CI): 2.49 -3.30) for diabetes among patients without other major risk factors (HCV, HBV, alcoholic liver disease, or hemochromatosis) for HCC ( 7 ).Other studies have focused on the association between HCC and obesity. It is estimated that 90 % of people with obesity have fatty liver disease, including NASH and cirrhosis ( 16 ). One study of over 19,000 patients found that the incidence of HCC was higher in obese (defi ned as BMI > 30 kg / m 2 ) patients than in nonobese patients (4.0 % vs. 3.0 % , respectively; P = 0.013), and that obesity was associated with a 65 % increased risk of developing HCC ( 13 ). Another large prospective cohort study of more than 900,000 individuals reported that the mortality rate from liver cancer was fi ve times greater among those with a BMI between 35 -40 compared with those with a normal BMI ( 5 ).A synergistic relationship has also been reported to exist between diabetes and other known risk factors for HC...

Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

“…A recent finding has demonstrated that genes involved in the lipid metabolism are crucial in cell transformation and over-expressed in tumor tissues [36]. Diabetes and non-alcoholic fatty liver disease may significantly increase the risk of developing HCC when other risk factors, such as hepatitis B virus, are present [37]. It is speculated that metabolic diseases, such as diabetes mellitus, and cancer may share common disrupted metabolic pathways [36].…”

Hepatocellular carcinoma screening practices and impact on survival among hepatitis B‐infected Asian Americans

“…It is unclear why high ALT levels were negatively associated with screening, though this effect was not observed among cirrhotic patients who attended liver subspecialty clinic. Limited studies have shown that noncirrhotic hepatitis B-infected Asians are less frequently screened for HCC compared to cirrhotics, and patients seen by gastroenterologists or hepatologists are more likely to receive regular HCC screening, with higher rates of screening rates reported among gastroenterologists compared to internists or family practitioners [13,19,21].…”

Nonalcoholic fatty liver disease: Evolving paradigms

“…NAFLD in those with T2D will follow a worse prognosis via hastened progression to NASH, liver cirrhosis and its complications and increased risk of developing NAFLD-HCC[ 43 , 207 - 210 ]. Specularly, concurrent NAFLD will often worsen the course of T2D[ 211 ].…”