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Background The Phase III ADVANCE study has shown clinical benefits for peginterferon beta-1a 125 µg dosed every 2 weeks versus placebo at 1 year in patients with relapsing-remitting multiple sclerosis (MS). This study assessed the impact of peginterferon beta-1a and disease factors on health-related quality of life (HRQoL) using data from ADVANCE. Methods HRQoL was assessed at baseline and 12, 24, and 48 weeks using the 29-item Multiple Sclerosis Impact Scale (MSIS-29) and other generic HRQoL measures. Changes in scores from baseline within each group and differences in mean change from baseline between groups were evaluated. Post-hoc mixed-effects repeated measures analyses were performed to assess the impact of confirmed disability progression and relapses, and the interactions of treatment and these MS events on HRQoL. Predictors with p ≥0.1 were excluded from the final models, unless they were clinically meaningful. Results Relapses and confirmed disability progression were major drivers of HRQoL. When comparing week 48 to baseline, in placebo-treated patients ( n =500), confirmed disability progression was associated with a 6.0-point worsening ( p <0.0001) of MSIS-29 physical scores, relative to a 1.9-point worsening ( p =0.044) with peginterferon beta-1a every 2 weeks ( n =512). Such findings were observed consistently with other generic HRQoL measures. Additionally, having a recent relapse (≤29 days before the HRQoL assessment) was associated with a 10.0-point worsening ( p <0.0001) of MSIS-29 psychological scores in placebo-treated patients, compared with a 3.5-point ( p =0.031) worsening with peginterferon beta-1a every 2 weeks. Conclusion Treatment with peginterferon beta-1a could help to improve or maintain HRQoL in addition to clinical outcomes. Trial registration : ClinicalTrials.gov: NCT00906399. [ABSTRACT FROM AUTHOR]

Background and aims It has been reported that 1,25(OH) 2 D 3 (1,25-VD 3 ) ameliorates the progression of nonalcoholic steatohepatitis (NASH). However, it is unclear whether 1,25-VD 3 plays a role in NASH induced by a choline-deficient (CD) diet. In this study, we investigated the roles of 1,25-VD 3 in the development and progression of NASH in rats induced by a CD diet. Methods and results Wistar rats with NASH induced by a CD diet were subjected to intraperitoneal injections of 1, 5, or 10 μg/kg of 1,25-VD 3 twice weekly for 12 weeks. The administration of 1,25-VD 3 decreased free fatty acids (FFAs), triglycerides (TGs), thiobarbituric acid-reactive substances (TBARS), the number of apoptotic cells, and the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the liver, and it improved liver histology, but it did not change the total antioxidant capacity (TAOC) in the liver. Interestingly, the level of CK18-M30 was decreased in the liver of model animals. Treatment with 1,25-VD 3 may restrain the downregulation of CK18-M30 in the liver and its release into the bloodstream, thus decreasing the level of serum CK18-M30. 1,25-VD 3 supplementation elevated the serum level of 25(OH)D 3 and the expression of VDR in the liver. The dose–effect relationship of 1,25-VD 3 indicated that 1,25-VD 3 slows down the development and progression of NASH induced by a CD diet, but higher doses of 1,25-VD 3 may lead to adverse effects. Conclusion The results suggest the presence of both antagonistic and adverse dose-dependent effects of the long-term supplementation of 1,25-VD 3 on NASH induced by a CD diet. [ABSTRACT FROM AUTHOR]

Background and Aims: It has been reported that 1,25(OH)2D3 (1,25-VD3) ameliorates the progression of nonalcoholic steatohepatitis (NASH). However, it is unclear whether 1,25-VD3 plays a role in NASH induced by a choline-deficient (CD) diet. In this study, we investigated the roles of 1,25-VD3 in the development and progression of NASH in rats induced by a CD diet.Methods and Results: Wistar rats with NASH induced by a CD diet were subjected to intraperitoneal injections of 1, 5, or 10 μg/kg of 1,25-VD3 twice weekly for 12 weeks. The administration of 1,25-VD3 decreased free fatty acids (FFAs), triglycerides (TGs), thiobarbituric acid-reactive substances (TBARS), the number of apoptotic cells, and the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the liver, and it improved liver histology, but it did not change the total antioxidant capacity (TAOC) in the liver. Interestingly, the level of CK18-M30 was decreased in the liver of model animals. Treatment with 1,25-VD3 may restrain the downregulation of CK18-M30 in the liver and its release into the bloodstream, thus decreasing the level of serum CK18-M30. 1,25-VD3 supplementation elevated the serum level of 25(OH)D3 and the expression of VDR in the liver. The dose-effect relationship of 1,25-VD3 indicated that 1,25-VD3 slows down the development and progression of NASH induced by a CD diet, but higher doses of 1,25-VD3 may lead to adverse effects.Conclusion: The results suggest the presence of both antagonistic and adverse dose-dependent effects of the long-term supplementation of 1,25-VD3 on NASH induced by a CD diet. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Numerous postoperative therapies for preventing recurrence of hepatocellular carcinoma (HCC) have been reported, but their efficacy remains controversial and knowledge about adverse effects is limited. A systematic review of randomized controlled trials (RCTs) was performed to gain a comprehensive picture of the efficacy and risks of these therapies. Methods: MEDLINE, EMBASE and the Cochrane Library were systematically searched through July 2011. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Results: A total of 2989 patients from 28 RCTs involving 10 postoperative therapies were included. For interferon therapy, the estimated RR for the 2-year recurrence rate was 0.84 (95% CI 0.73–0.97, P = 0.02) and the overall survival (OS) was 1.15 (95% CI 1.07–1.22, P < 0.001). Postoperative therapy with the vitamin K2 analog did not lead to a significant reduction in the 1-year recurrence rate, with a pooled RR of 0.60 (95% CI 0.28–1.27, P = 0.18). However, it did slightly improve the 1-year OS, with a pooled RR of 1.03 (95% CI 1.00–1.05, P = 0.03). Transarterial chemotherapy with or without embolization, adoptive immunotherapy and heparanase inhibitor PI-88 therapy may delay tumor recurrence. The effects of acyclic retinoid, lipiodol-iodine-131 and tumor vaccine treatment were promising but require further study. All postoperative therapies except interferon administered intramuscularly were well tolerated by the majority of patients. Conclusions: Use of adjuvant interferon is definitely associated with an increase in OS. Postoperative therapies involving acyclic retinoid, lipidol-iodine-131, or tumor vaccine may improve the OS of patients with HCC after curative treatment. [Copyright &y& Elsevier]