Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?

Abstract

Recently, several epidemiologic observations have suggested that obesity might be an independent risk factor for certain malignancies such as breast cancer, colon cancer, renal cell carcinoma, and esophageal adenocarcinoma. However, there are no studies examining the risk of hepatocellular carcinoma (HCC) in obesity. The aim of the present study was to determine whether obesity is an independent risk factor for HCC in patients with cirrhosis. Explanted liver specimens from a national database on patients undergoing liver transplantation were examined for HCC, and the incidence was compared among patients with varying body mass indices according to the etiology of cirrhosis. A multivariate analysis was used for controlling other potentially confounding variables such as age and sex. Among 19,271 evaluable patients, the overall incidence of HCC was 3.4% (n ‫؍‬ 659) with a slightly higher prevalence among obese patients compared with lean patients. Obesity was an independent predictor for HCC in patients with alcoholic cirrhosis (odds ratio [OR], 3.2; 95% CI, 1.5-6.6; P ‫؍‬ .002) and cryptogenic cirrhosis (OR, 11.1; 95% CI, 1.5-87.4; P ‫؍‬ .02). Obesity was not an independent predictor in patients with hepatitis C, hepatitis B, primary biliary cirrhosis, and autoimmune hepatitis. The higher risk of HCC in obese patients is confined to alcoholic liver disease and cryptogenic cirrhosis. In conclusion, more frequent surveillance for HCC may be warranted in obese patients with alcoholic and cryptogenic cirrhosis. However, as this study is based on patients with advanced cirrhosis, our findings need to be confirmed in a broader population of individuals with cirrhosis. (HEPATOLOGY 2002;36:150-155.)

Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies

“…We identified 11 eligible cohort studies (Møller et al, 1994;Wolk et al, 2001;Nair et al, 2002;Calle et al, 2003;Samanic et al, 2004Samanic et al, , 2006Batty et al, 2005;Kuriyama et al, 2005;Oh et al, 2005;Rapp et al, 2005;N'Kontchou et al, 2006), of which 7 on overweight (with a total of 5037 cases) (Calle et al, 2003;Batty et al, 2005;Kuriyama et al, 2005;Oh et al, 2005;Rapp et al, 2005;N'Kontchou et al, 2006;Samanic et al, 2006) and 10 on obesity (with a total of 6042 cases) (Møller et al, 1994;Wolk et al, 2001;Nair et al, 2002;Calle et al, 2003;Samanic et al, 2004Samanic et al, , 2006Batty et al, 2005;Oh et al, 2005;Rapp et al, 2005;N'Kontchou et al, 2006) were suitable for metaanalysis. Characteristics of the studies are shown in Table 1.…”

“…Two studies were based on standardized incidence ratio (Møller et al, 1994;Wolk et al, 2001). Two studies consisted of patients with cirrhosis (Nair et al, 2002;N'Kontchou et al, 2006).…”

“…In a sensitivity analysis excluding the two studies that consisted of patients with cirrhosis (Nair et al, 2002;N'Kontchou et al, 2006), the summary relative risks were 1.07 (95% CI: 1.01 -1.15) for overweight and 1.85 (95% CI: 1.44 -2.37) for obesity. With stratification by assessment of obesity, the summary relative risks for the association between obesity and liver cancer were 2.15 (95% CI: 1.66 -2.77) for studies based on measured or self-reported weight and height (Nair et al, 2002;Calle et al, 2003;Batty et al, 2005;Oh et al, 2005;Rapp et al, 2005;N'Kontchou et al, 2006;Samanic et al, 2006) and 1.61 (95% CI: 1.14 -2.27) for studies based on a discharge diagnosis of obesity (Møller et al, 1994;Wolk et al, 2001;Samanic et al, 2004).…”

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

“…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 ).…”

Inherent growth advantage of (pre)malignant hepatocytes associated with nuclear translocation of pro-transforming growth factor α

“…Thus, initiation causes a change in the growth-regulatory network that becomes evident after the first replication cylce of GSTp þ cells. Treatment with tumour promoters, such as the progestin cyproterone acetate (CPA), or increased food intake further increases cell replication in preneoplasia, which is analogous to human hepatocarcinogenesis driven by anabolic steroids or overnutrition (Schulte-Hermann et al, 1990;Grasl-Kraupp et al, 1994;Fiel et al, 1996;Nair et al, 2002). This enhanced sensitivity of liver preneoplasia towards the various growth stimuli could result from an altered uptake, production and/or processing of endogeneous growth regulatory factors by the premalignant cell compartment.…”