[16] In addition, the reduction in fibrinolysis increases deposition of fibrin in liver parenchyma and sensitizes it to LPS-induced necrosis and inflammation.[17] Thus, the present findings represent a potential link between NAFLD

and cardiovascular risk and liver fibrosis. Some interesting questions arise from this study. The contribution of gender, the PAI-1 4G/5G polymorphism, and ethnicity to PAI-1 variance in NAFLD remains to be elucidated.[14] The low prevalence of overweight (7.9% with body mass index [BMI] <30), advanced fibrosis (9.1%), and the exclusion of diabetic subjects (9%) limits the applicability of the results to these subgroups that are typical of “office” cases of NAFLD. However, perhaps Fostamatinib manufacturer the most important but unanswered question

from a cross-sectional study is whether NAFLD-associated increases in PAI-1 promotes cardiovascular disease or liver fibrosis selleck inhibitor progression. Conceivably, such considerations are more academic than of clinical consequence, and not easily answered without carefully designed longitudinal studies. For example, PAI-1 is consistently associated with obesity, insulin resistance, diabetes mellitus, and a sedentary lifestyle, all predictors for the development of both NASH and cardiovascular disease. But will defining an independent link of NAFLD to cardiovascular risk change NAFLD treatment? The benefit of pharmacological strategies for primary prevention of cardiovascular disease in NAFLD patients (e.g., antiplatelet agents) has not been demonstrated. The cost-effectiveness of this measure depends on demonstrating that NAFLD poses a significant additional cardiovascular mortality risk compared to traditional factors. On the other hand, implementing specific therapy with vitamin E or pioglitazone in NAFLD could theoretically be an attractive intervention to reduce cardiovascular risk. However, properly designed prospective studies and validation of new interventions need to be performed 上海皓元医药股份有限公司 before recommending their use for this specific indication, considering their adverse effects and costs. In the meantime, the “simplest” approach would be early initiation of lifestyle intervention

therapies. Although long-term compliance continues as its major drawback, the weight-independent reduction of PAI-1 observed in obese diabetic subjects undergoing lifestyle intervention should be an additional incentive to promote it, and hopefully modify cardiovascular risk and adverse liver-related outcomes.[18] Francisco Barrera, M.D.1,2 “
“I read with great interest the article by Park etal.,1 who found that a vitamin C deficiency ameliorated liver fibrosis via the up-regulated expression of peroxisome proliferator-activated receptor gamma in senescence marker protein 30 (SMP30) knockout mice. The results are interesting and shed light on the possible mechanisms underlying the attenuated liver fibrosis of SMP30 knockout mice.