Also, the clinical significance of the relative contribution of individual features to the decrease in NAS remains unknown. Thus, given these gaps in knowledge, changes in NAS are inferior to reversal of steatohepatitis

as an endpoint that reflects an improvement in the natural history of the disease. Although the authors provide a justification for their sample size estimations, Bafilomycin A1 supplier given the variability in the severity of the individual parameters included in the NAS and the variability due to sample size estimation, the study is somewhat underpowered to make definitive conclusions about treatment efficacy in NASH. Also, several subjects did not complete the study or or did not receive an end-of-treatment biopsy. Finally, only 5 of 55 subjects had type 2 diabetes; diabetes is a major risk factor for disease progression to cirrhosis. These factors limit the ability to draw definitive conclusions about the efficacy of pentoxifylline for NASH or the generalizability of the data to those at greatest risk of developing progressive disease. It is interesting to note that pentoxifylline did not meet the proof of concept sufficient to demonstrate biological effect, i.e., a decrease Napabucasin mw in circulating TNF-α levels or markers of insulin sensitivity (adiponectin, insulin sensitivity index). These would suggest that either the assays were inaccurate or there are alternate mechanisms underlying the observed decrease in NAS. Our

view is that the latter is more likely. Notably, the improvement in NAS was driven by a decrease in steatosis. This could reflect changes in diet and exercise; however, these data were not collected or provided. Also, the clinical implications of a major decrease in steatosis are unknown. It is also possible that pentoxifylline has novel, hitherto unknown, mechanisms of action. This remains

to be experimentally verified. So, is pentoxifylline a magic bullet or a smoking gun in the treatment of NASH? In conclusion, the list of drugs that can improve histological characteristics of NASH seems to be growing. Although Dr. Zein’s study provides impressive evidence of improvement in steatosis and inflammation, pentoxifylline did not significantly improve hepatocellular ballooning. Although a trend for improved fibrosis was noted, it is critically important medchemexpress not to overinterpret the data in a study with a small sample size. However, these data show enough preliminary evidence for a potential ability of pentoxifylline to improve NASH to set the stage for future, fully powered, phase 3 clinical trials. “
“On-treatment responses to antiviral therapy are used to determine duration of therapy in patients being treated for genotype 1 hepatitis C virus infection. Such use of response-guided therapy has successfully reduced exposure of patients to the side-effects of pegylated interferon and ribavirin without jeopardizing overall treatment success.