Of these patients, 340 subsequently developed HCC. The risk of HCC in patients with chronic HCV increased in proportion to BMI with a hazard ratio of 1.86 for overweight http://www.selleckchem.com/products/ch5424802.html patients and 3.10 for obese patients as compared to underweight patients.90 Recently, Konishi et al. published a study of a cohort of chronic HCV patients without a previous diagnosis of diabetes mellitus.91 The study demonstrated that the presence of diabetes mellitus, as evidenced by a positive 75 g oral glucose tolerance test, independently increased the risk of HCC development in patients with chronic HCV.91 NAFLD and its

associated risk factors appear to act synergistically with other conditions to promote HCC.92 The data suggesting that hepatic steatosis, obesity, and diabetes mellitus increase the risk of HCC development in chronic HCV strengthens the notion that they are risk factors for

the development of HCC in NASH. Treatment of these conditions related to NASH may decrease the risk of carcinogenesis associated with chronic HCV, and should be further evaluated. Multiple case reports of HCC in the setting of NASH have been published and reviewed in the literature (Table 3).8, 52, 57, 93-109 Male patients make up the majority of cases with a mean age at diagnosis of 66.7 (range = 45-82). The patients are typically older at presentation than patients with HCC related to other RG7420 manufacturer chronic liver diseases. This older age at presentation correlates to reports of older ages at presentation in patients with CC and HCC compared to alcohol-related, HBV-related, and HCV-related HCC controls.50 The majority of the patients with HCC in the setting of NASH also have underlying diabetes (64%), obesity (58%), or this website other manifestations of the metabolic syndrome which is consistent with previous findings. Patients typically have large, well-differentiated tumors at the time of presentation

which may be secondary to a delayed diagnosis. Up to 50% of patients have HCC at the time of initial referral, and rarely patients present with HCC in the absence of cirrhosis.8, 93, 94, 96, 101, 105-109 The fact that HCC can arise in the setting of NASH without underlying cirrhosis raises the interesting possibility that carcinogenesis can occur in NAFLD in the absence of advanced liver disease.108 Three recent case studies of patients with HCC in the setting of NASH support the findings of previous case reports.57, 107, 109 Hashizume et al. reviewed nine patients with HCC in NASH. The majority of patients were male and the median age of diagnosis was 71.5 years. All of the patients had diagnoses of diabetes, hypertension, or hypertriglyceridemia, and the majority showed clinical evidence of insulin resistance and the metabolic syndrome. Three of nine patients developed HCC without evidence of underlying cirrhosis. The review supports the associations of age, cirrhosis, diabetes, and obesity with the risk for HCC.107 Chagas et al.