POSTERS Methods: The association between genetic polymorphism of PNPLA3 (rs738409) and the degree of liver steatosis, stage of fibrosis, and subsequent development of HCC was analyzed in 157 chronic hepatitis C patients. Results: The frequency of homozygote for risk allele G (GG) was 20%, and heterozygote (CG) was 51%. Steatosis was present in 87% vs. 59% in CG/GG vs. CC genotypes (p = 0.003). Advanced stage of fibrosis (METAVIR stage 4) was present in 22% of genotype GG compared to 6% in CG/CC (p = 0.015). The cumulative incidence of HCC development was significantly higher in GG genotype compared to CG or CC (hazard ratio: 2.5, 95% CI: 1.1–5.5, p = 0.02). The 5 year incidence of HCC development was the 12.8%, 6.3%, and 2.3% for GG, CG, and CC genotype respectively (p = 0.018). Conclusions: The risk allele G of the PNPLA3 rs738409 SNP is associated with steatosis, advanced fibrosis, and higher risk for the development of HCC among patients with chronic hepatitis C. P753 DYNAMIC EVALUATION OF NK SUBSET DISTRIBUTIONS IN CHRONIC HIV/HCV COINFECTION – A PILOT STUDY M. Petrova1 , O. Angelova1 , M. Aleksandrova1 , M. Muhtarova1 , I. Elenkov2 , V. Kamburov3 , M. Nikolova1 . 1 Immunology, NCIPD, 2 AIDS Department, SHATIPD, 3 Lyulin Hospital, Sofia, Bulgaria E-mail:
[email protected] Background and Aims: Although a number of studies indicate impaired NK cell differentiation and function in persistent infections, conclusive data regarding NK-related subsets in HIV/HCV co-infection are still scarce. Methods: We compared the effect of 12-month cART on the restoration of NK-subsets in sex- and age-matched groups of HIV mono-infected (group A, n = 12) and HIV/HCV co-infected (B, n = 13) patients. A control group of HIV–HCV− healthy individuals was constituted according to NCLS-criteria. Absolute counts (AC) and percentages of peripheral CD4+T, CD8+T, B, and NK-cells, NKT, CD56high and CD56low NK subsets were determined by 6-color flow cytometry (FACS Canto II). Results: At baseline, none of the studied parameters differed between the patients groups. The level of CD56hi NK, unlike NK CD56low and NKT subsets, in both groups was lower as compared to controls (average 0.45 and 0.37 vs. 0.72, p < 0.05 for both). The effect of cART on the restoration of CD4 AC was comparable in mono and co-infected (CD4AC at 12 mo 442 vs. 422 cells/ml, p > 0.05). The levels of NKT and CD56low NK-cells did not show dynamics in both groups. CD56high NK-cells were restored to control levels only in group A, resulting in a higher level of regulatory NK in the monoinfected as compared to co-infected patients after 12 months of cART (average 1.4 vs 0.4, p < 0.01). Conclusions: This pilot study indicates that NK cell subset dynamics may be an informative monitoring parameter in HIV/HCV patients subjected to cART. Further studies on innate immunity are warranted to elucidate the mechanisms of immune restoration in HIV/HCV co-infection. P754 INCREASING RATE OF UNTREATED HCV INFECTION IN HIV–HCV COINFECTED PATIENTS J. Chas1 , S. Le Nagat1 , A. Adda1 , C. Amiel2 , G. Pialoux1 . 1 Unit of Infectious Diseases, 2 Unit of Virology, CHU Tenon, Paris, France E-mail:
[email protected] Background and Aims: Despite acceptable treatment success in this real-life setting, HCV remains untreated in the majority of patients. Methods: All HIV–HCV coinfected patients consulting at the Unit of Infectious Diseases of Tenon Hospital (France, Paris) were identified using a clinical database (Diamm G® ) in September 2013. This is a S322
retrospective study to assess reasons of non-HCV therapy initiation and epidemiological profile of these HIV–HCV patients. Results: Among 2 855 HIV patients screened, 364 HIV–HCV coinfected patients were identified whereas 84 (23%) patients remained untreated. This study analysed 77/84 of them, 7 being lost of follow-up: male/female: 60/17, mean age: 48.43 years, HCV genotype (GT) was predominantly GT-1 (47%) and GT-4 (26%), hepatic fibrosis stage was: F0 14%, F1 29%, F2 26%, F3/F4: 22%. Main reasons deferral of HCV treatment was waiting for new treatment (43%), minor hepatic stage (17%), psychiatric diseases (10.5%), patient retention (9%), treatment unproposed by physician (6.5%), drugs abuse (6.5%), cirrhosis child C (4%). Usually, 36 of them should be treated by the HCV Protease Inhibitors available according to current treatment guidelines, only 1 patient benefited from compassionate use of sofosbuvir, and 7 patients could be included in a direct-acting antiviral (DAA) Protocol. Conclusions: This large cohort study provides evidence for increasing under-treatment of chronic HCV infection in HIV patients awaiting the newer DAA despite that HCV related liver disease has emerged as a significant and increasing cause of morbidity and mortality in HIV positive patients. P755 HEPATITIS C COINFECTION INDEPENDENTLY INCREASES CARDIOVASCULAR RISK IN HIV-INFECTED PATIENTS J.V. Fernandez-Montero1 , E. Vispo1 , P. Barreiro1 , C. De Mendoza1 , C. Triano2 , B. Cornelli3 , V. Soriano1 . 1 Infectious Diseases, Hospital Carlos III, Madrid, 2 Universidad de Navarra, Pamplona, Spain; 3 Universita di Pavia, Pavia, Italy E-mail:
[email protected] Background and Aims: There is growing evidence that chronic HCV infection plays a major role in the development of extrahepatic complications. The impact of chronic hepatitis C on the development of extrahepatic complications has scarcely been examined in HIV/HCV-coinfected patients. Methods: A retrospective study was carried out to assess the effect of coinfection with HBV and/or HCV on the risk of cardiovascular events in a large cohort of HIV-infected patients. As end-point, a composite event of cardiovascular disease was used, including myocardial infarction, angina pectoris, stroke and death due to any of them. Results: Data from a total of 1147 HIV-infected patients (mean age 42 years, 81% males, 46% IDU) were analyzed. Mean followup was 82±17 months. At baseline, 521 patients (45.4%) were HCV+, 85 (7.4%) were HBsAg+ and 17 (1.5%) had anti-HDV. All HCV-Ab+ patients were HCV-RNA+ but 13 (2.5%) that had cleared HCV spontaneously. Overall 3 patients died due to cardiovascular disease while 23 suffered a first episode of coronary ischemia or stroke. HIV/HCV-coinfected patients showed a significantly higher incidence of cardiovascular death or events than HIV-monoinfected patients (3.3% vs 1.1%, p = 0.01) and shorter event-free survivals (100.4 months; 95% CI: 99.6–101.2 vs 101.4 months; 95% CI: 101–102, p = 0.04). After adjusting for demographics, virological variables, and classic cardiovascular risk factors, HCV coinfection was associated with cardiovascular disease or death (HR 2.43; 95% CI: 1.01–5.9; p = 0.04). Conclusions: Chronic hepatitis C is associated with increased cardiovascular events and mortality in HIV-infected patients. Primary prevention of cardiovascular disease should be stressed in this population.
Journal of Hepatology 2014 vol. 60 | S215–S359