11, 15 Japanese investigators first reported that the risk of HCC was reduced significantly in patients with HCV who responded to interferon (both sustained and transient).11

Since then, other groups have find more also shown a protective effect against HCC in patients with HCV who responded to interferon.15 Japanese investigators also showed glycyrrhizin, an aqueous extract of licorice root with anti-inflammatory activity, reduces both cirrhosis and HCC risk in patients with chronic HCV infection.15 A few other chemopreventive agents have also been reported such as vitamins K1, K2, and K3, and coffee and tea, but these observations await prospective validation. Two secondary chemopreventive agents have been studied in patients. The first is interferon-alpha after liver resection in HCV-induced cirrhosis.19 Although there was no difference in HCC recurrence overall, there was a 50% reduction in late recurrence rate in the treatment arm in HCV-pure (no previous contact with HBV) patients who adhered to treatment. The other agent reported to have a beneficial

effect in secondary chemoprevention is acyclic retinoic acid.20 In a prospective, randomized, controlled trial in Japan, acyclic retinoic acid was given for 12 months to patients treated with resection or local ablation of HCC. After 68 months of follow-up, survival rates were 74% in Selleck FK506 patients treated with acyclic retinoic acid versus 46% in the untreated group.15 However, the effectiveness of retinoid in secondary chemoprevention remains to be confirmed by another group. Up to now, the data are compelling that this website for patients infected with HBV and HCV, response

to antiviral therapy correlates with reduced risk of HCC. However, for those nonresponders and for the patients with cirrhosis who are not infected with HBV or HCV, the options are unclear. Ideal chemopreventive agents would be safe to use chronically and affordable for the population at risk. Of the numerous agents studied in animal models, not many have been examined, even in small trials in humans. Currently, of 246 active clinical trials on adult HCC (searched at http://clinicaltrials.gov), three trials examine prevention of HCC recurrence after surgical resection or local ablative therapy, and only one study examines primary chemoprevention of HCC. This study seeks to determine whether 24 weeks of SAMe treatment in HCV-infected patients can reduce serum levels of des-gamma carboxyprothrombin and alpha-fetoprotein and is expected to end on December 31, 2010. Given the magnitude of the problem, more emphasis on and support for conducting these studies are sorely needed. Agents that have been shown in multiple animal models to be effective, safe, and affordable are ideal candidates for these studies. Because different etiologies are likely to have distinct mechanisms in the pathogenesis of HCC, it may also be important to test these agents in models designed for different etiologies, such as HCV and HBV transgenic mice.