Early menopause is associated with lack of response to antiviral therapy in women with chronic hepatitis C.

BACKGROUND & AIMS: Chronic hepatitis C (CHC) and liver fibrosis progress more rapidly in men and menopausal women than in women of reproductive age. We investigated the associations among menopause, sustained virologic response (SVR), and liver damage in patients with CHC. METHODS: We performed a prospective study of 1000 consecutive, treatment-naïve patients 18 years of age and older with compensated liver disease from CHC. Liver biopsy samples were analyzed (for fibrosis, inflammation, and steatosis) before patients received standard antiviral therapy. From women (n = 442), we collected data on the presence, type, and timing of menopause; associated hormone and metabolic features; serum levels of interleukin-6; and hepatic tumor necrosis factor (TNF)-α. RESULTS: Postmenopausal women achieved SVRs less frequently than women of reproductive age (46.0% vs 67.5%; P < .0001) but as frequently as men (51.1%; P = .283). By multivariate regression analysis, independent significant predictors for women to not achieve an SVR were early menopause (odds ratio [OR], 8.055; 95% confidence interval [CI], 1.834-25.350), levels of γ-glutamyl transpeptidase (OR, 2.165; 95% CI, 1.364-3.436), infection with hepatitis C virus genotype 1 or 4 (OR, 3.861; 95% CI, 2.433-6.134), and cholesterol levels (OR, 0.985; 95% CI, 0.971-0.998). Early menopause was the only independent factor that predicted lack of an SVR among women with genotype 1 hepatitis C virus infection (OR, 3.933; 95% CI, 1.274-12.142). Baseline levels of liver inflammation, fibrosis, steatosis, serum interleukin-6 (P = .04), and hepatic TNF-α (P = .007) were significantly higher among postmenopausal women than women of reproductive age. CONCLUSIONS: Among women with CHC, early menopause was associated with a low likelihood of SVR, probably because of inflammatory factors that change at menopause.

Knowledge of Nutrition and Physical Activity Guidelines is Not Associated with Physical Function in Dutch Older Adults Attending a Healthy Ageing Public Engagement Event.

Purpose: Evidence-based guidelines on nutrition and physical activity are used to increase knowledge in order to promote a healthy lifestyle. However, actual knowledge of guidelines is limited and whether it is associated with health outcomes is unclear. Participants and Methods: This inception cohort study aimed to investigate the association of knowledge of nutrition and physical activity guidelines with objective measures of physical function and physical activity in community-dwelling older adults attending a public engagement event in Amsterdam, The Netherlands. Knowledge of nutrition and physical activity according to Dutch guidelines was assessed using customized questionnaires. Gait speed and handgrip strength were proxies of physical function and the Minnesota Leisure Time Physical Activity Questionnaire was used to assess physical activity in minutes/week. Linear regression analysis, stratified by gender and adjusted for age, was used to study the association between continuous and categorical knowledge scores with outcomes. Results: In 106 older adults (mean age=70.1 SD=6.6, years) who were highly educated, well-functioning, and generally healthy, there were distinct knowledge gaps in nutrition and physical activity which did not correlate with one another (R2=0.013, p=0.245). Knowledge of nutrition or physical activity guidelines was not associated with physical function or physical activity. However, before age-adjustment nutrition knowledge was positively associated with HGS in males (B= 0.64 (95% CI: 0.05, 1.22)) and having knowledge above the median was associated with faster gait speed in females (B=0.10 (95% CI: 0.01, 0.19)). Conclusion: Our findings may represent a ceiling effect of the impact knowledge has on physical function and activity in the this high performing and educated population and that there may be other determinants of behavior leading to health status such as attitude and perception to consider in future studies.

LCT-13910C>T polymorphism-associated lactose malabsorption and risk for colorectal cancer in Italy.

BACKGROUND: The activity of epithelial lactase (LCT) associates with a polymorphism 13910 bp upstream the LCT-encoding gene (LCT-13910C>T). The relationship between LCT-13910C>T polymorphism and risk for colorectal cancer is unclear. AIMS: We examined the relationship between the LCT-13910C>T polymorphism causing lactose intolerance and risk for colorectal cancer/polyps onset in the Italian population. PATIENTS AND METHODS: 793 subjects (306 with colorectal cancer, 176 with polyps and 311 controls) were genotyped for the LCT-13910C>T variant by TaqMan real time-PCR. RESULTS: Lactose malabsorption linked to the CC genotype did not associate with an increased risk for either colorectal cancer (OR=1.041; 95% CI=0.751-1.442; p=0.868) or polyps (OR=0.927; 95% CI=0.630-1.363; p=0.769). There was no association with colorectal cancer/polyps site. 60% of the subjects overall bore the CC genotype. CONCLUSION: In the Italian population the LCT-13910C>T polymorphism is not associated to the risk for colorectal cancer or polyps.

Individually administered or co-prescribed thiopurines and mesalamines for inflammatory bowel disease.

Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases) by the advent of the novel biological molecules with anti-cytokine activity.

Mesalamine for inflammatory bowel disease: recent reappraisals.

Derived from the historical molecule sulfasalazine, mesalamine has remained one of the mainstays for treatment of inflammatory bowel disease in the last 50 years. Recent advancement in both clinical and basic research has led to reappraise the drug under two crucial aspects. Firstly, there has been a re-evaluation of the chemo-protective effect of mesalamine against sporadic colorectal cancer. Evidence that inflammation plays a strong role in tumor induction from one side, and demonstration that mesalamine can touch on specific molecular steps enhancing apoptosis on the other side have re-shaped the indications of mesalamine for ulcerative colitis. Secondly, the role of thiopurines (azathioprine and 6-MP) in the maintenance of remission of ulcerative colitis has been reiterated by the results of several clinical trials. During attempts at clarifying the reasons why certain patients appear to be resistant to thiopurines, it was interestingly found that mesalamine can interfere thiopurine metabolism, causing an increased blood concentration of the specific immunosuppressive metabolites and a sequential enhancement of drug effectiveness. Mesalamine is therefore being studied as a means to overcome the genetically determined resistance to thiopurines. Such sharpened indications have reiterated attention to correct dosing: the results of controlled trials have shown mesalamine to be fully effective at twice the traditional daily dosage (4.8 grams instead of 2.4). The attendant problems of compliance seem to find solution in the availability of multi-matrix system formulations. This mesalamine story reminds us that in the absence of an etiological target capable to guide research to trace one abrogating molecule, (as it has happened for viral hepatitides for example), treatment of inflammatory bowel disease remains anti-inflammatory in nature and thus multifaceted. Besides justified use of cutting-edge technology to find novel molecules, smart re-evaluation of what is already in our hands can sometimes bring about unexpected breakthroughs.