SUMMARY BackgroundNon-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH.
Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis.
A pilot study of a 48-week course of pioglitazone demonstrated significant improvements in the biochemical and histological features of nonalcoholic steatohepatitis (NASH). The aim of the study was to assess the effects of stopping pioglitazone. Twenty-one patients with NASH were treated with pioglitazone (30 mg/day) for 48 weeks and underwent baseline and end-of-treatment evaluation including liver biopsy. Thirteen patients were followed for at least 48 weeks after stopping therapy and 9 underwent repeat liver biopsy. Statistical comparisons were made to evaluate whether discontinuation of pioglitazone resulted in a reversal of improvements seen on therapy. Stopping pioglitazone was associated with subsequent elevation in serum alanine aminotransferase levels (from 34 ؎ 13 to 70 ؎ 39 IU/l), decrease in adiponectin (from 9.7 ؎ 9.1 to 5.1 ؎ 4.5 g/ml), worsening insulin sensitivity (HOMA Index: from 2.9 ؎ 1.8 to 5.5 ؎ 5.4), and increase in total hepatic fat (from 30% ؎ 32% to 71% ؎ 33%) despite no change in average body weight compared to the end of treatment. Repeat liver biopsy in 9 patients revealed significant worsening of parenchymal inflammation (from 1.2 ؎ 0.7 to 2.9 ؎ 1.1) and steatosis (from 0.9 ؎ 0.6 to 2.1 ؎ 1.3) but no change in fibrosis (from 1.1 ؎ 1.2 to 1.2 ؎ 1.3). NASH was again present on liver biopsy in 7 patients. Conclusion: These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects. (HEPATOLOGY 2007;46: 424-429.)See Editorial on Page 285 N onalcoholic steatohepatitis (NASH) is an inflammatory liver disease associated with progressive liver injury which can eventually lead to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. 1 The etiology of NASH is thought to be related to insulin resistance and the metabolic syndrome. 2 NASH is closely associated with obesity and thus may represent the most prevalent chronic liver disease in the United States. 3,4 Several strategies aimed at improving insulin resistance have been employed in clinical trials for NASH, one being controlled weight loss using diet and exercise. This approach has had limited success in those patients who are able to lose and maintain weight loss in the long term. The improvement in histology with weight loss is primarily in hepatic steatosis rather than inflammation and fibrosis. [5][6][7] Thus far, pharmacological therapy aimed at weight loss has been disappointing, and histological data on the effects of weight-loss medications are lacking. 8 A more sustained option is bariatric surgery which has been shown to promote marked weight loss, decrease insulin resistance, and improve liver histology in patients with NASH. 9 However, for most patients with NASH, an invasive surgical procedure with major metabolic effects is not an appropriate option.Drug therapy primarily aimed at improving insulin resistance presents a possible option for patien...
Daily, full dose of sofosbuvir plus simeprevir for 12 weeks of therapy appears to be well tolerated in patients with ESRD on HD or GFR <30 ml/min. Most common AEs resembled those of healthier CHC patients without significant renal impairment. The cure rates obtained in this cohort treated with sofosbuvir and simeprevir are dramatically superior to any previous treatment regimen studied & published in this special patient population.
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