C.F. Perno

392 SPECIFIC HBSAG GENETIC-DETERMINANTS ARE ASSOCIATED WITH OCCULT HBV-INFECTION IN VIVO AND HBSAG-DETECTION

Background and Aim: Measuring serum HBVDNA levels after diagnosing acute hepatitis B is not a routine procedure. Its kinetics, however, could have a significant prognostic importance for the future development of the infection. The aim of our study is to detrmine whether HBVDNA levels could have prognostic value as far as the outcome of the infection is concerned: self-limited disease, fulminant or self-limited infection Material and methods: Our study included a dynamic examination of HBVDNA in 45 patients with acute HBV infection with different outcome – recovery, protrached course and fulminant hepatitis as two forms that differ from the self-limited HBV infection. HBVDNA was measured on the 1, 2, 7, 30, 60, 90, 180 day after admission to the hospital using Taq Man HBVDNA Real-time PCR. Results: HBVDNA was found in all patients. In fulminant cases relatively high levels of HBVDNA were found from the very beginning (above 10,000,000 IU/ml) and they were HBeAg(−). In patients who recovered and became HBsAg(−) replication reached maximal levels in the beginning of the symptomatic phase. With the recovery form the symptoms it fell and its disappearance marked the fall of the ALT levels and negativation of the HBsAg. The fall of HBVDNA on the 7 day from the admission to the hospital and the following disappearance in the range of the 60 day proved to be predictive for the self-limited course. In patients with protrached hepatitis HBVDNA proved to be with relatively higher levels drom the beginning (p < 0.016, F = 6.196) especially in the HBeAg(+) cases. These levels persisted at the time of 90 and 180 day with following chronification. Conclusion: The follow-up of the replication showed, that in the majority of cases the elimination of the virus becomes in the first 2 months. The persistence of the viremia on the 60 day necessitates its further examination due to the risk of chronification. High risk for protrached course is observed in the anicteric HBeAg(+) cases with relatively high replication (above 100,000,000 IU/ml).

P691 KEY PATTERNS OF HBsAg MUTATIONS CORRELATE WITH MECHANISMS UNDERLYING LEVELS OF SERUM HBVDNA

Background and Aims: Every year globally WHO reports nearly 20 million Hepatitis E virus (HEV) infections. The disease has potential to cause massive epidemics. The reservoir of HEV during interepidemic period in India is not well characterized, with evidences of deficient zoonotic links. Further, the sporadic cases usually lack history of contact with clinically overt HEV patients. In the present context the occurrence of subclinical HEV as a possible reservoir of infection in endemic region was evaluated. Methods: Blood samples were collected from 67 apparently-healthy individuals and 10 acute viral hepatitis (AVH) patients during two HEV outbreaks in North India. The serum samples were tested for anti-HEV IgM, IgG, HEV-IgG avidity-index, HEV viral-load and conventional-PCR followed by sequencing and phylogenetic analysis. Results: A total of 14 (20.89%) apparently-healthy individuals showed presence of both anti-HEV IgM and IgG. Based on HEVIgG avidity-index, 9 apparently-healthy individuals (64.28%) had secondary-exposure, 4 (28.57%) had primary-exposure, while one patient had intermediate-avidity. Subclinical subjects with primaryexposure had significantly higher anti-HEV IgM index as compared to secondary-exposure. Viral-load in clinically jaundiced patients was significantly higher as compared to subclinical subjects (p < 0.0001). Phylogenetic analysis showed HEV sequences retrieved from subclinical individuals (Genotype 1a) clustered along with AVH patients reported in the same outbreak suggesting matched origin. The significantly low viral-load in subclinical subjects hints towards the dose dependency for progression of clinical manifestation. Conclusions: We document subclinical passage of HEV occurs without producing clinically overt hepatitis goes un-noticed which, in turn helps maintaining the virus in nature possibly leading to its endemicity.

166 HCV DIVERSITY AND FIBROSIS PROGRESSION: NS5A AND CORE VARIANTS CORRELATE WITH SEVERITY OF HCV RECURRENCE AFTER LIVER TRANSPLANTATION

Results: The overall 1-, 5and 10-year posttransplant survival rates, stratified by the composite risk score are presented in table 1. More than half (53.6%) of patients had at least one of the risk factors (obesity, renal dysfunction or advanced age). Patients with two or more risk factors (score ≥2) experienced a significantly higher covariate-adjusted risk of death compared to patients with zero (HR: 5.9, 95%CI: 2.3–14.3; p < 0.001) or one (HR: 2.6, 95%CI: 1.3–5.6; p = 0.009) risk factor.

63 CORRELATION OF EARLY DETECTION OF HCV NS3-RESISTANCE AND VIROLOGICAL FAILURE IN PATIENTS TREATED WITH TRIPLE THERAPY INCLUDING TELAPREVIR OR BOCEPREVIR

63 CORRELATION OF EARLY DETECTION OF HCV NS3-RESISTANCE AND VIROLOGICAL FAILURE IN PATIENTS TREATED WITH TRIPLE THERAPY INCLUDING TELAPREVIR OR BOCEPREVIR V. Cento, V.C. Di Maio, D. Di Paolo, F. De Luca, V. Micheli, M. Tontodonati, M.C. Bellocchi, L. Carioti, D. Armenia, F. De Leonardis, F.P. Antonucci, G. Madeddu, C. Magni, C. Sarrecchia, S. Babudieri, G. Parruti, M. Angelico, G. Rizzardini, C.F. Perno, F. Ceccherini-Silberstein. University of Rome Tor Vergata, University Hospital of Rome Tor Vergata, Roma, Hospital Sacco of Milan, Milan, Infectious Disease Clinic of Chieti, Chieti, University of Sassari, Sassari, Pescara General Hospital, Pescara, Italy E-mail: ceccherini@med.uniroma2.it

430 KEY GENETIC SIGNATURES IN THE WHOLE pre-S1/Pre-S2/S GENE CORRELATE WITH HBV-INDUCED CARCINOGENESIS BY AFFECTING HBsAg SECRETION AND RELEASE

430 KEY GENETIC SIGNATURES IN THE WHOLE pre-S1/Pre-S2/S GENE CORRELATE WITH HBV-INDUCED CARCINOGENESIS BY AFFECTING HBsAg SECRETION AND RELEASE V. Svicher, M. Neumann-Fraune, C. Mirabelli, R. Salpini, V. Cento, V.-C. Di Maio, A. Bertoli, C. Alteri, M. Aragri, C. Gori, V. Micheli, G. Gubertini, P. Trimoulet, H. Fleury, J. Vecchiet, N. Iapadre, A. Barlattani, T. Mari, C. Pasquazzi, C. Sarrecchia, F. Ceccherini-Silberstein, M. Andreoni, M. Angelico, J. Verheyen, C.-F. Perno. University of Rome Tor Vergata, Rome, Italy; University of Cologne, Cologne, Germany; National Institute for Infectious Diseases ‘L. Spallanzani’, Rome, “L. Sacco” Hospital, Milan, Italy; Hopital Pellegrin Tripode, Bordeaux, France; “SS Annunziata” Hospital, Chieti, “S Salvatore” Hospital, L’Aquila, “S Giacomo” Hospital, “Regina Margherita” Hospital, “S Andrea” Hospital, Rome, Italy; University of Essen, Essen, Germany E-mail: valentina.svicher@uniroma2.it

CARATTERIZZAZIONE DEI PROFILI DI RESISTENZA A LAMIVUDINA ED ADEFOVIR IN PAZIENTI CON EPATITE B CRONICA

Le infezioni da Herpesvirus negli stati di immunodepressione rappresentano un grave problema sanitario dovuto al rischio concreto di malattia severa. Una peculiare caratteristica dei virus erpetici é infatti la capacità di stabilire nell’ospite, a seguito di un’infezione primaria più o meno acuta, infezioni persistenti tutta la vita, con frequenti riattivazioni a cui si associano gravi quadri patologici. Discriminante è lo stato immunitario che condiziona sia l’insorgenza che la gravità del processo infettivo: infatti i virus erpetici sono abili nell’evadere il sistema immunitario interagendo con cellule deputate alla risposta umorale o adattiva spesso già pesantemente inficiate dalla patologia di base di tali pazienti. Nel corso degli anni 2004-2007 sono stati monitorati 39 pazienti (24 maschi, 15 femmine, range di età 1,578), di cui 21 sottoposti a trapianto di midollo osseo, che presentavano disordini ematologici di varia natura: 14 affetti da LLA, 7 LNH, 4 LH, 4 MM, 2 LLC, 2 Linfoma Linfoblastico a Cellule T, 1 BLLC, 1 Linfoma KI1, 1HLH, 1 LC, 1 LMA, 1MDS. I pazienti sono stati monitorati da un minimo di due ad un massimo di trenta volte nel corso della sorveglianza virologica che è stata condotta mediante tecnica PCR Real Time e nested per HSV1, HSV2, CMV, EBV, HHV7, HHV8, VZV su campioni ematici, accompagnati o meno da campioni pertinenti la patologia in atto. Dall’analisi virologica l’82% dei pazienti è risultato positivo per almeno uno degli otto virus erpetici ricercati eziologicamente associati a quadri di polmonite interstiziale, neutropenia, lesioni mucocutanee, encefalite e trasformazione neoplastica. Nelle malattie oncoematologiche la frequenza di infezioni virali è elevata a causa dello stato di neutropenia e immunosoppressine derivante dall’intensità del regime di condizionamento pre-trapianto: il riconoscimento dell’agente eziologico e la terapia mirata e precoce sono presidi salvavita resi oggi disponibili dall’utilizzo di tecniche molecolari. 090