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Faster Progression (faster + progression)
Selected AbstractsHFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in the Czech populationHEPATOLOGY RESEARCH, Issue 9 2007Pácal Aim:, To determine the prevalence of selected HFE polymorphisms (C282Y, H63D and S65C) among patients with chronic viral hepatitis B and C and to investigate their role in the progression of liver disease. Methods:, A total of 207 subjects with chronic B or C viral hepatitis and 243 healthy controls were enrolled in the case,control study. Cases were further classified into three groups according to the clinical stage of liver disease: (A) virus carriers; (B) compensated liver disease; and (C) decompensated liver disease. HFE polymorphisms were detected by polymerase chain reaction-based methodology. Fisher's exact test, ,2 and Kruskal,Wallis tests were used to test for differences in variables studied between groups. Haplotypes were inferred in silico and their distribution compared by permutation test. Modified survival (time-to-event) analysis was used to test for the differences in the progression to the decompensated liver disease in carriers of C282Y wild-type versus mutated genotypes. Results:, The frequency of HFE genotypes, alleles and haplotypes differed neither between HBV nor HCV patients versus controls. In HCV subjects: (i) the frequency of the 282Y allele was significantly higher in the (C) group compared to (B) group (12.5 vs 2.2%, respectively, P = 0.002, Fisher's exact test); and (ii) carriers of the 282Y mutation exhibited significantly faster progression to decompensated liver disease than wild-type carriers (P = 0.044, log,rank test). Conclusion:, Carriage of the minor HFE C282Y polymorphism is associated with decompensated liver disease and its earlier onset in the subjects with chronic viral hepatitis C in the Czech population. [source] Human immunodeficiency virus,hepatitis C coinfection: swapping new problems for newer onesINTERNAL MEDICINE JOURNAL, Issue 7 2001J. Sasadeusz Abstract Recent successes in HIV therapy have uncovered other health problems for HIV-infected individuals. Hepatitis C has become an especially significant problem, partly due to its faster progression in an immunocompromised setting. In addition, the higher viral loads in coinfected patients likely result in more efficient perinatal and perhaps even sexual transmission. Therapy has largely been neglected, despite data suggesting its efficacy in HIV,HCV coinfected patients. Studies of combination interferon and ribavirin studies are lacking, although underway. A major concern is the potential inactivation of certain thymidine analogues by ribavirin. Some antiretroviral therapies, such as ritonavir, indinavir and nevirapine, may enhance liver toxicity in coinfected patients and should be avoided if possible. The role of chronic low-grade liver function abnormalities remains uncertain and requires further investigation. (Intern Med J 2001; 31: 418,421) [source] Liver transplantation for HCV cirrhosis: Improved survival in recent years and increased severity of recurrent disease in female recipients: Results of a long term retrospective studyLIVER TRANSPLANTATION, Issue 5 2007Luca S. Belli In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis has been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score > 3) in different transplant years; and 2) model the effects of pre- and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT in almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan,Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P = 0.0001) and female gender of recipient (P = 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P = 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival was observed in more recent years but the cumulative probability of developing severe recurrent disease remained unchanged. The combination of a female recipient receiving an older graft emerged as a strong risk factor for a severe recurrence. Liver Transpl, 2007. © 2007 AASLD. [source] Interaction between smoking and the stromelysin-1 (MMP3) gene 5A/6A promoter polymorphism and risk of coronary heart disease in healthy menANNALS OF HUMAN GENETICS, Issue 5-6 2002S. E. HUMPHRIES Smoking is a major risk factor for coronary heart disease (CHD), but this risk may be modified by an individual's genotype. A common functional 5A/6A polymorphism in the promoter of the stromelysin-1 (matrix metalloproteinase 3, MMP3) gene has been identified. The 6A allele has been consistently associated with faster progression of angiographically determined CHD, while the 5A allele has recently been associated with risk of acute myocardial infarction (MI) in patients with unstable angina. To date there has been no prospective study of the relationship of this genotype to CHD risk in smokers and non-smokers. DNA was available from 2743 middle-aged men, free of CHD at baseline, recruited through nine general practices in the UK for prospective surveillance. To date there have been almost 24000 person-years of follow-up with 125 CHD events (fatal and non-fatal MI, sudden coronary death, need for coronary artery surgery or new major ECG Q-wave abnormality). Men with events were each matched for age, practice and cholesterol level with three healthy men. Smoking habit was determined by questionnaire. 5A/6A genotype was determined using a heteroduplex generator method. Associations between genotype and disease outcome, according to smoking status, were assessed using conditional logistic regression. Overall, current smoking was associated with a relative risk (RR) of 1.99 (95% CI 1.30,3.06) as compared with never-smokers and ex-smokers combined (p<0.002). In non-smoking men, and after adjustment for conventional risk factors, compared with the 5A5A group, the RR was 1.37 (0.64,2.94) in those with the genotype 5A6A and 3.02 (1.38,6.61) in those with the genotype 6A6A. Smoking increased risk 1.4 fold in the 5A6A group to 1.91 (1.84,4.36), by 1.3 fold in the 6A6A group to 4.01 (1.57,10.24), but by 3.81 fold (1.54,9.40) in the 5A5A group (smoking,genotype interaction p = 0.01). The data indicate a key role for stromelysin in the atherosclerotic process. Men with the stromelysin genotype 5A5A represent 29% of the general population, and their high risk, if smokers, provides a further strong argument for smoking avoidance. [source] | ||||||||||