sa1088 impact of chronic hepatitis c infection on mortality in chronic hemodialysis patients: a...
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stest compared with only 47% Asian cases with positive anti-HCV (Figure 1). For Asiancases, the most common risk factors were blood transfusion (25%), acupuncture (13%),and exposure to dirty needles (8%). Illicit drug use (IDU) and body tattoo were presentonly in a minority of patients (3% and 4%, respectively) (Figure 2). For non-Asian cases,the most common risk factors were IDU and body tattoo (41% and 33%, respectively). Onmultiple logistic regression, independent predictors for positive anti-HCV test in Asians wereacupuncture/exposure to dirty needles (OR=11.3, p<0.0001), tattoos (OR=10.5, p=0.002),and history of blood transfusion (OR=5.1, p<0.0001). For both Asian and Non-Asian, caseswere more likely to have a family history of HCV compared to controls (6% vs. 1% [p<0.0001]and 15% vs. 2% [p=0.02], respectively). Conclusion: Compared to non-Asians, Asians arelikely to present without commonly known risk factors for infection with HCV (47%). Inaddition to well-known risk factors for HCV infection such as blood transfusion and tattoos,acupuncture and exposure to dirty needles are also independent risk factors of HCV infection.Asians coming from endemic areas should be screened for HCV even when commonlyknown risk factors for Western patients are not present.
Figure 1. Proportion of patients with any known risk factors, by ethnicities
Figure 2. Risk exposures in cases and controls, by ethnicities
Sa1088
Impact of Chronic Hepatitis C Infection on Mortality in Chronic HemodialysisPatients: A Meta-AnalysisAugustine Salami, Ivo C. Ditah, Vidyasagar Marupakula, Charles O. Jaiyeoba, ZeenatBhat, Syed-Mohammed Jafri
Background: The prevalence of chronic hepatitis C virus infection (HCV) is significantlyhigher in hemodialysis (HD) patients. There is accumulating data suggesting that HCV isassociated with increased mortality in HD patients. However, this increase is likely confoun-ded by several co-morbidities and incident complications in these patients. While cardiovas-cular disorders remain the leading cause of death in HD patients, it is unknown whetherthis is true in HCV positive HD patients. AIM: Evaluate the impact of chronic HCV infectionon mortality in hemodialysis patients. Methods: A systematic search of PubMed,Scopus,andWeb of Science databases from January 1980 to September 2011 was done. Identified articleswere manually reviewed for additional references. Only peer-reviewed articles comparingmortality in HCV positive to HCV negative patients who must have been on hemodialysisfor at least six months were eligible for inclusion. Data were abstracted independently by2 authors. Inter-reviewer discrepancies were resolved by joint review of the original article.Outcome measures evaluated included all-cause mortality, liver disease-related mortality,
S-966AASLD Abstracts
cardiovascular related mortality and infection related mortality. Summary risk ratios werecomputed using the fixed effects or random effects model if there was suggestion of heterogen-eity between the studies. Heterogeneity was assessed using the Cochrane's Q and I2 statistics.Publication bias was evaluated using the Begg's and Egger's tests, and visual inspection ofcorresponding funnel plots. A sensitivity analysis using Duval and Tweedie's “trim-and-fill”method was also performed. Results: A total of eight studies, all of which were cohort studiesmet the inclusion criteria. The total number of patients was 41,067, with 4,499 being HCVpositive. The overall pooled risk ratio for all-cause-mortality was 1.15 with a 95% CI of1.08-1.22;P<0.001. Liver dysfunction was the leading cause of mortality in HCV patientswith an RR of 9.18(95% CI 4.25 -19.83, P<0.001). The sensitivity analysis incorporatinghypothetical studies using the Duval and Tweedie “trim-and-fill” method persistently showeda statistically significant result with RRo 6.45(95%CI 3.27-12.72;P<0.001). There was nostatistically significant difference in mortality due to cardiovascular and infectious etiologiesbetween the 2 groups with risk ratios of 1.04(95% CI 0.91-1.18) and 1.14(95% CI 0.89-1.47), respectively. Table 1 summarizes the results of the various outcomes. Conclusion:Thisstudy suggests that HCV infection in long term HD patients is associated with an increasedrisk of mortality. While cardiovascular disorders are known to be the leading cause ofmortality in HD patients, liver dysfunctions may be the leading cause in HCV infected HDpatients. Management of HCV in HD needs to be considered a priority.Table 1: Summary of pooled effects, heterogeneity and publication bias
* Sensitivity analysis done because of wide confidence interval in liver related mortalityshowed Liver related mortality by Duval and Tweedie “trim-and-fill” Pooled effect = 6.45(95% 3.27-12.72), P <0.001
Sa1089
Proteomic Analysis of ITPA SNP rs1127354 Chronic Hepatitis C (Ch-C)Patients Indicates Differential Regulation of Apoptosis Pathway ComponentsJ. Michael Estep, Maria Stepanova, Arian Afendy, Emanuel Petricoin, Ancha Baranova,Zobair M. Younossi
Background:Anemia is an important and common side effect of pegylated interferon alfaand ribavirin (PEG-IFN+RBV). The ITPA SNP rs1127354 “T” allele confers protection againstRBV-induced anemia in CH-C patients undergoing PEG-IFN/RBV treatment compared tothe more common “C” allele. Previously, we have established that the apoptosis pathwaycomponents are significantly differentially regulated at the mRNA level during PEG-IFN/RBV treatment in patients with differing rs1127354 genotypes. Aim: The aim of this studywas to investigate proteomic profiles of CH-C patients with different rs1127354 genotypes.Methods: From peripheral blood lymphocyte samples which were collected from 53 CH-Cpatients, protein lysates were extracted and then used for Reverse Phase Protein Microarrayanalysis, which quantitatively measured the relative phosphorylation of the signaling molec-ules. DNA was extracted from whole blood and genotyped for rs1127354 by PCR usingtetra-primer refractory PCR method. Pathway analysis was conducted using MetCore GeneGoand Ariadne Pathway Analysis software packages. Results: MetaCore Pathway Analysis indic-ated the significant differential regulation of the apoptosis pathway (P=2.88*10^-7). Signalsfor antiapoptotic molecules CD5L, CD247, and STAT3 were increased in the CT group vs.the CC group by 8.4%, 18.3%, and 25.8%, respectively. Furthermore, in the CT group weobserved a decrease in expression of 15 apoptosis-related molecules, 10 of which (LCK,IL4, IL1b, IL10, STAT2, PKLR, PRKCZ, PRKCD, RPS6KB1, and JAK1) are considered pro-apoptotic. Additionally, in the CT group, decreases of IL5 and IL10 signals were observed.IL5 and IL10, known to promote hemolysis, were lower in the heterozygous CT group ascompared to the CC by 3% and 9.9% respectively. Conclusions: Proteomic investigationssupport differential regulation of apoptosis as the mechanism by which ITPA genotypeconfers protection from PEG-IFN/RBV treatment associated anemia.
Sa1090
Low Rate of Hepatitis C Virus Reinfection After Sustained VirologicalResponse in Injected Drug UsersSpilios Manolakopoulos, Hariklia Kranidioti, Stylianos Karatapanis, Ioannis Goulis,Efrosini Tsirogianni, Melanie Deutsch, Olga Anagnostou, Dimitrios Margaritopoulos,George V. Papatheodoridis, Dimitrios Pectasides
Background and aims The majority of intravenous drug users (IVDUs) are infected with thehepatitis C virus (HCV) and they may be the source of infection of many other subjectsdue to their risky behavior. Despite the fact that the majority of IVDUs in Greece are infectedwith HCV genotype 3 and have similar response rates to non-IVDU patients, only a minorityof them start antiviral treatment. The risk of reinfection following therapy is one of the mainreasons for not initiating antiviral treatment. We evaluated the rate of HCV reinfection inpast - current IVDUs following sustained virological response (SVR) having received antiviral treatment in a multidisciplinary program. Methods We analyzed data from a cohortof IVDUs patients with HCV infection attending a multidisciplinary supervised program inthree liver Greek Units. Inclusion criteria were: A. chronic hepatitis C infection, b. previousantiviral treatment with development of SVR, c.) at least 12 months interval after end of