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Finally, a comparison between studies was not possible because of the lack of pretreatment stratification of patients for predictive factors such as age, gender, severity of disease and comorbidities that increase the progression of viral hepatitis. Thus, results reporting the efficacy of PEG-IFN-�� in preventing HBV-related HCC diverge greatly and there are several limitations to most studies with positive results. In a study of 233 HBeAg-positive http://www.selleckchem.com/products/sch772984.html IFN-treated patients (8.1% with cirrhosis) and 233 matched controls (10.7% with cirrhosis) [22], the incidence of HCC appeared to be reduced by therapy (2.7% vs. 12% in controls, P? http://www.selleck.cn/products/z-vad-fmk.html vs. 58.9% controls; P?=?0.0086), not in patients without (2.1% treated vs. 2.3% controls). Thus, the apparent beneficial effect of PEG-IFN-�� in reducing HCC was paradoxical, limited to patients with pre-existing cirrhosis. In another study of 313 patients with cirrhosis, the cumulative occurrence of HCC was significantly lowered by the ��intermittent�� administration of IFN compared with those receiving no therapy at 5 (7.0% vs. 19.6%) and 10?years (17.0% and 30.8%) [23]. However, this study was limited by the lack of a fixed treatment protocol as well as of a consistent number of patients without cirrhosis. Other studies may not have http://www.selleckchem.com/products/dabrafenib-gsk2118436.html shown that IFN helped prevent HCC in HBV patients because hepatitis Be antigen (HBeAg) seroconversion was used as the endpoint of treatment. In this case [24-26], most patients continued to have detectable serum HBV DNA after HBeAg clearance, ie HBV DNA was the relevant risk factor for HCC [27]. PEG-IFN-�� did not influence the development of HCC in studies in patients with mild or moderate fibrosis, [25, 26, 28, 29], possibly because unlike in patients with cirrhosis, the risk of HCC in patients without cirrhosis and with chronic hepatitis B is ��diluted�� reflecting a shorter duration of infection or a lack of important predictive factors for HCC such as cirrhosis. Finally, six meta-analyses have evaluated the chemoprevention of HCC in patients who receive IFN to fight viral hepatitis and results are again conflicting (Table 1). Results for chemoprevention were negative in three studies [30-32] and positive in the other three [33-35]. However, the latter studies were flawed by a lack of efficacy of PEG-IFN in patients without cirrhosis in one study, exclusion of patients with normal ALT in another and a lack of efficacy of PEG-IFN in Europeans in another.