42 Patients with CC were, on average, 8 years older than patients with HCV at the time of development of cirrhosis and about 3 years older at the time when HCC was detected.42 Emerging evidence has established multiple independent risk factors for the development of HCC including obesity, diabetes, and iron deposition (Table 2). These factors also increase the risk for the development of NASH, a probable precursor to CC. It is well established that HCC develops in the presence of chronic liver

disease, typically associated with cirrhosis from HBV, HCV, and/or alcoholic liver disease. Cirrhosis is the most important single risk factor for HCC and is present in about 80% of patients with HCC, regardless of underlying liver disease.57 As noted previously, NASH likely HKI-272 mouse accounts for a large proportion of the idiopathic cirrhosis that makes up 6.9%-50% of underlying liver disease in patients with HCC in developed countries.7 This conclusion is further supported by evidence of linking common risk factors for NASH with risk factors for HCC. Obesity has been established

as a significant risk factor for the development of various malignancies, including liver cancer.49, 58-60 selleck kinase inhibitor A large, prospective mortality study by the American Cancer Society61 demonstrated increased cancer mortality with increased body weight. The death rates from all types of cancers among the heaviest patients in the cohort (patients with a BMI > 40 kg/m2) were 52% higher for men and 62% higher for women compared with patients

of normal weight. These significant mortality rates included death from esophageal, stomach, colorectal, liver, gallbladder, pancreatic, prostate, and kidney cancer as well as leukemia, non-Hodgkin’s lymphoma, and multiple myeloma. Compared to patients with normal BMI, the relative L-NAME HCl risk (RR) of mortality from liver cancer was 1.68 times higher in women and 4.52 times higher in men with BMI > 35 kg/m2. Death from liver cancer among obese males demonstrated the highest RR of all the cancers in the study. This confirmed the results of another population-based study from Denmark of more than 40,000 obese patients, which showed that the RR of liver cancer was increased to 1.9 compared to the general population.62 A study from Korea published in 2005 examined the relationship between BMI and various cancers in 781,283 men without a prior diagnosis of cancer.63 The patients were followed over a 10-year period. Korean men with a BMI > 30 kg/m2 had a 26% increase in risk for all types of cancer compared to men with a normal BMI.63 An RR of 1.53 was demonstrated for HCC in obese males compared to normal controls, even after controlling for HBV infection, which is the most common cause of HCC in Korea.63, 64 A review of data from 19,271 patients who underwent orthotopic liver transplant in the United States between 1991 and 2000 showed the overall incidence of HCC was 3.4% with a slightly higher incidence among obese patients at 4.0%.