In fact, in the study by Everhart et al.,13 obesity was significantly associated on univariate analysis with the development of outcomes (histological and/or clinical). The mechanism underlying the association between obesity and the development of clinical decompensation in cirrhosis is unknown. In our study, 1-year changes in portal pressure (as determined by HVPG) were significantly different among BMI groups, with HVPG decreasing significantly in normal weight and overweight patients but not in obese patients (in whom it showed a slight, not statistically significant increase) (Fig. 2). HVPG failed to decrease in obese patients despite

the fact that half of them received a potent nonselective beta-blocker (timolol).20 Moreover, only a minority of obese patients had a satisfactory hemodynamic response (HVPG decrease ≥10%) at 12 months. This observation suggests that Selleck BMS-777607 the mechanism

by which obesity leads to a greater incidence of clinical decompensation HM781-36B chemical structure is, at least in part, due to an increase in HVPG, as portal hypertension is responsible for the clinical complications that define this late stage of cirrhosis. In this regard it is worth noting that adipose tissue in obesity is known to acquire a proinflammatory, profibrogenic, and proangiogenic phenotype resulting in the production of adipokines and cytokines (leptin, interleukin (IL)-1 and tumor necrosis factor alpha)21-23 with deleterious vascular effects on hepatic inflammation, fibrogenesis, and angiogenesis, which may mediate a further worsening of intrahepatic resistance and portal hypertension.24, 25 From an epidemiologic point of view, it is interesting to note that over two-thirds of our patients with compensated cirrhosis were

overweight or obese and that this proportion is similar to that of the general population both in Europe and in the US.4 It could therefore be predicted that, as has been occurring in the general population, obesity selleck kinase inhibitor will increase further among patients with compensated cirrhosis. With this perspective and given the increased risk of clinical decompensation in obese patients with cirrhosis, the implementation of measures aimed at reducing obesity in patients with chronic liver diseases should be considered a priority. From a clinical point of view our findings have important implications. Up to now the only modifiable lifestyle-associated risk factor for decompensation in cirrhosis was alcohol ingestion in patients with alcoholic cirrhosis. In a similar way, our data suggest that overweight plays an important and independent role in the progression of compensated to decompensated cirrhosis, and might become a new nonpharmacological target for preventing clinical events in this population.