[40, 50-52] In line with previous results,[53, 54] the presence of steatosis, which was observed in 62% of patients, was independently associated with older age, increased BMI, and hyperglycemia, but not with viral features, such as HBeAg status, and viral load, thus suggesting that metabolic alterations

are click here the leading cause of steatosis in CHB, as in the general population and in CHC,[55] whereas differently from hepatitis C, the virus itself does not play a role.[54] The high prevalence of steatosis in the present series[54] can be explained by the high prevalence of metabolic risk factors and the inclusion criteria (e.g., allowance of excessive alcohol consumption). The major finding of the present

study is the I148M polymorphism representing a genetic determinant of steatosis susceptibility in CHB. Similarly to what was observed in CHC,[40, 50] the 148M allele was an independent predictor of steatosis of any degree, but it was even more strongly associated, together with increased BMI, with the presence of severe steatosis, Selleck KPT330 increasing the risk by approximately 6-fold. Interestingly, the effect was particularly evident in the 35% of patients with acquired cofactors, such as a positive history of alcohol intake and/or severe overweight, whereas it was negligible in low-risk teetotalers with normal weight, which is consistent with the hypothesis that severe steatosis HAS1 results from the interaction of different predisposing conditions, including

the 148M PNPLA3 allele.[41] Recently, an interaction between the PNPLA3 I148M polymorphism and tea drinking in the pathogenesis of steatosis have been reported in an epidemiological study conducted in Asia.[56] Although a limitation of the present study is that tea and coffee drinking was not quantitatively assessed, tea drinking was not frequent in Italian patients, and both coffee and tea consumption were not associated with steatosis (not shown). Of note, increased BMI and active alcohol consumption were also independently associated with advanced fibrosis, and a nonsignificant trend for an association between advanced disease and severe steatosis (or the NAS) was also observed, thus leaving open the possibility that altered hepatic lipid metabolism is a risk factor for fibrosis progression also in CHB,[15, 17] although prospective studies are required for confirmation. As a result of the many confounders influencing disease history, the PNPLA3 I148M polymorphism was not associated with fibrosis severity, but, despite the relatively large number of well-characterized biopsied patients included, the power of the study was not sufficient to formally test the interaction between genetic and acquired risk factors in the pathogenesis of liver fibrosis.