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Chronic Intermittent Hypoxia is associated with Liver Damage and Atherosclerosis in Patients with Non-alcoholic Fatty Liver Disease
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Abstracts / Digestive and Liver Disease 47S (2015) e43–e66
F-11 CLINICAL RELEVANCE OF NEXT GENERATION SEQUENCING ON BASELINE DETECTION OF MINORITY RESISTANCE ASSOCIATED VARIANTS IN HCV-1 PATIENTS TREATED WITH PROTEASE INHIBITORS D. Armenia 1 , L. Carioti 1 , V.C. Di Maio 1 , M.C. Bellocchi 1 , D. Di Paolo 2 , F. Guerrieri 3 , L. Calvo 4 , V. Cento 1 , M. Tontodonati 5 , V. Micheli 6 , F. De Leonardis 2 , M. Aragri 1 , E. Polilli 7 , A. Manunta 8 , C. Magni 6 , F.P. Antonucci 1 , F. De Luca 1 , C. Sarrecchia 9 , A. Bertoli 1 , I. Lenci 2 , S. Francioso 2 , M.M. Santoro 1 , J. Vecchiet 5 , S. Marenco 10 , A. Picciotto 10 , L. Nosotti 11 , F. Morisco 12 , S. Bruno 13 , M. Puoti 14 , S. Babudieri 8 , M.S. Mura 8 , M. Andreoni 9 , G. Rizzardini 6 , G. Parruti 7 , M. Levrero 4 , M. Angelico 2 , C.F. Perno 1 , F. Ceccherini-Silberstein 1 1 Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy 2 Hepatology Unit, University Hospital of Rome “Tor Vergata”, Rome, Italy 3 Center for Life Nano Science, CNLS@SAPIENZA, IT 4 La Sapienza” University, Rome, Italy 5 Infectious Disease Clinic, Chieti, Italy 6 Hospital Sacco of Milan, Milan, Italy 7 Infectious Disease Unit, Pescara General Hospital, Pescara, Italy 8 Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy 9 Infectious Disease, University Hospital of Rome “Tor Vergata”, Rome, Italy 10 S. Martino University Hospital, Genoa, Italy 11 Hepatology Unit, National Institute of Health, Migration and Poverty, Rome, Italy 12 University “Federico II”, Naples, Italy 13 Internal Medicine, Gastroenterology and Hepatology, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy 14 Hospital Niguarda Ca’Granda, Milan, Italy
Background and Aims: This study aims to evaluate the clinical relevance of next-generation-sequencing on the baseline detection of minority resistance-associated-variants (RAVs) in chronic HCV-1 infected patients treated with telaprevir/ boceprevir + pegIFN/ribavirin. Methods: NS3-protease sequences of 25 selected patients (18 virological-failures and 7 responders) treated with telaprevir (N = 20) or boceprevir (N = 5) + pegIFN/ribavirin were analyzed. Detection of NS3-RAVs (V36ALM/T54AS/V55A/Q80 K/R155KT/ A156STV/V170A) was performed by Sanger-sequencing, 454junior-pyrosequencing (UDPS) and MiSeq-illumina (MiSeq). UDPS sequences were analyzed by a home-made-pipeline (>3,000 sequences/patient; cut-off > 0.1%); Miseq sequences were analyzed by VirVarSeq (>40,000 sequences/patient; cut-off ≥ 0.3%). Results: At baseline, 5/25 patients (20%) presented NS3-RAVs by Sanger, UDPS and MiSeq (Q80K = 3; T54S = 1; V36L + Q80K = 1, prevalence >98%). Of them, 4 patients experienced virologicalfailure and 1 (with Q80 K) achieved sustained-virological-response (SVR). Additional baseline minority-RAVs (Q80 K/V170A) were found by both UDPS and MiSeq in 2 patients, all with prevalence < 2.6%. However, their presence was not directly associated with virological-failure. Indeed, 1 previous-null-responder with
baseline minority Q80 K failed telaprevir-triple-therapy with different RAVs (V36AM + R155K + T156ST). The other patient, previous partial-responder, with baseline minority V170A achieved SVR. By using MiSeq, analyzing a larger number of sequences (median[IQR]:843,492[342,499-1,006,108]), a high number of NS3RAVs (N = 43,cut-off ≥0.3%) were detected in 19/25 patients (76%). In particular, V55A was the most prevalent RAV detected (52%), followed by V36A (36%), Q80 K (28%), and T54A (8%). The presence of these mutations at baseline was similar between responders and virological-failures. Interestingly, a unique HCV-1a infected patient previous-non-responder with 10 baseline minorityRAVs (V36A:0.41%; T54S:0.33%; V55A:0.47%, Q80 K:0.36%; R155 K:0.55%; R155 T:0.59%; A156S:1.19%; A156 T:0.64%; A156 V:0.50%, V170A:0.57%, with a median[IQR] mutational-load of 19,567[15,870-21,987] IU/ml) failed telaprevir-triple-therapy, with A156 T (week-2) and later with V36M + R155 K (week-10). Conclusions: Both UDPS and MiSeq detected baseline RAVs at very low frequency. However, these variants were not necessarily detected at virological-failure. Further investigations are needed to clarify the clinical relevance of minority RAVs at frequency below 1%. http://dx.doi.org/10.1016/j.dld.2015.01.105 F-12 CHRONIC INTERMITTENT HYPOXIA IS ASSOCIATED WITH LIVER DAMAGE AND ATHEROSCLEROSIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE S. Petta 1 , O. Marrone 2 , D. Torres 3 , M. Buttacavoli 4 , C. Cammà 1 , V. Di Marco 1 , A. Licata 1 , A. Lo Bue 2 , G. Parrinello 3 , A. Pinto 3 , A. Selvaggio 2 , A. Tuttolomondo 3 , A. Craxì 1 , M. Bonsignore 4 1 Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy 2 National Research Council, Institute of Biomedicine and Molecular Immunology, Palermo, Italy 3 Sezione di Medicina Interna, DiBiMIS,University of Palermo, Palermo, Italy 4 Sezione di Pneumologia, DiBiMIS,University of Palermo, Palermo, Italy
Background: Obstructive sleep apnea syndrome(OSAS) has been reported as a new risk factor for metabolic disturbances, including cardiovascular alterations. Growing data are also available among bariatric nonalcoholic fatty liver disease(NAFLD) patients on the impact of obstructive sleep apnea syndrome OSAS on liver damage in NAFLD. We assessed whether OSAS is associated with severity of liver fibrosis and carotid atherosclerosis in NAFLD patients without morbid obesity. Methods: 126 consecutive biopsy-proven(Kleiner score) NAFLD patients assessed for anthropometric, biochemical, and metabolic features underwent ultrasonographic carotid assessment and STOP BANG questionnaire for estimate of low or high OSAS risk. A carotid plaque was defined as a focal thickening > 1.3 mm at the level of either common and internal carotid arteries or bifurcations. 50 patients accepted to perform nocturnal cardiorespiratory polygraphy, and OSAS was defined if the as an apnea/hypopnea index AHI index was≥5. Results: The prevalence of high OSAS risk was similar in patients without and with polygraphy(76% vs 68%,p = 0.17). Among these last subjects who underwent polygraphy 50% had OSAS. The prevalence of an OSAS was significantly higher in patients with, than in
Abstracts / Digestive and Liver Disease 47S (2015) e43–e66
those without, F2-F4 fibrosis compared to those without(72% vs 44%, respectively; p = 0.04). After correction for confounders, significant fibrosis was associated with S02 mean levels≤95% mean oxyhemoglobin saturation(SaO2) levels < 95%(OR 3.21,95%C.I. 1.027.34;p = 0.04). Similarly, the prevalence of OSAS was slightly higher in patients with, than in those without, carotid plaques compared to(64% vs 40%;p = 0.08). After correction for confounders, the association between carotid plaques were associated with T90(time spent with SaO2 < 90%) >1% was maintained(OR 6.30,95%C.I.1.0212.3;p = 0.01). Conclusions: In NAFLD patients without morbid obesity OSAS was highly prevalent and indexes of oxygen saturation were independent indicators of the severity of liver fibrosis and of carotid atherosclerosis risk. These data, if further validated, could suggest to look at for OSAS in all NAFLD patients, considering OSAS as a potential additional therapeutic target for NAFLD. http://dx.doi.org/10.1016/j.dld.2015.01.106 F-13 IFNL4 POLYMORPHISMS PREDICT SUSTAINED RESPONSE AND HBSAG CLEARANCE IN INTERFERON TREATED HBEAG NEGATIVE CHRONIC HEPATITIS B PATIENTS E. Galmozzi 1 , P. Lampertico 1 , F. Facchetti 1 , F. Invernizzi 1 , G. Mangia 1 , M. Vigano 2 , R. Soffredini 1 , M. Colombo 1 1
Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 2 Liver Unit, Ospedale San Giuseppe, University of Milan, Milan, Italy Introduction and Aim The recently identified interferon lambda 4 (IFNL4) gene harbors the dinucleotide variant rs368234815-TT/G, a genetic marker of outcome to IFN-based therapy of HCV infection. The IFN-4 protein, which can be generated only by carriers of the rs368234815-G allele, is thought to counteract IFN responsiveness by inducing a weak expression of interferon-stimulated genes. Three nonsynonymous variants of the IFNL4 gene (rs73555604, rs142981501 and rs117648444) could affect the IFN-4 protein. We aimed to explore whether IFNL4 polymorphisms impact on response to IFN-based treatment in the setting of chronic hepatitis B (CHB). Materials and Methods IFNL4 gene was sequenced by Sanger method on genomic DNA extracted from whole blood of 126 HBeAg-negative CHB patients treated with either standard or pegylated-IFN-␣ and followed-up for 11 years (range 1-17) posttreatment. Results Sustained response rates to IFN were not significantly different between the 62 carriers of the rs368234815TT/TT (IFN-4 eliminating) genotype and the 64 carriers of the rs368234815-G (IFN-4 generating) allele (31% vs 17%, p = 0.079). Since the only nonsynonymous variant identified in our cohort, the Pro70Ser rs117648444-C/T polymorphism, was exclusively associated with carriers of the IFN-4 generating allele, these 64 patients were stratified into rs117648444-CC (IFNl-4 wild-type, n = 45) and rs117648444-CT/TT (IFNl-4 mutated, n = 19) genotypes. Sustained responses among IFN-4 eliminating (rs368234815-TT/TT) and IFN-4 mutated (rs117648444-CT/TT) genotypes (n = 81) were significantly higher than those in the 45 IFN-4 wild-type subjects (33.3% vs 9%, OR = 4.8, 95%CI 1.6-15.0, p = 0.006). Yet, in the multivariate analysis the combination of IFN-4 eliminating and IFN-4 mutated genotypes independently predict both sustained response to interferon (OR = 5.33, 95%CI 1.7-16.8, p = 0.004) and off treatment
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HBsAg clearance (HR = 4.3, 95%CI 1.5-12.3, p = 0.007). Pretreatment serum HBV-DNA was the only other independent predictor of HBsAg loss (HR = 0.61, 95%CI 0.43-0.87, p = 0.007). Conclusions IFNL4 polymorphisms independently predict sustained response to interferon and off treatment HBsAg clearance in HBeAg negative CHB patients. http://dx.doi.org/10.1016/j.dld.2015.01.107 F-14 NON-INFECTIOUS CO-MORBIDITIES IN HIV PATIENTS CO-INFECTED WITH HEPATITIS VIRUSES: AN ANALYSIS FROM THE CALABRHIV STUDY GROUP M.C. Postorino 1 , F. Luciani 2 , C. Mangano 3 , M.S. Carpentieri 3 , P. Scerbo 4 , A. Priamo 4 , G. Berardelli 5 , R. Marino 6 , A. Vallone 6 , N. Serrao 7 , V. Pisani 1 , C. Costa 1 , A. Terremoto 2 , G. Foti 3 , L. Cosco 4 , M. Calderazzo 5 , D. Corigliano 5 , P. Scordo 1 , C. Torti 1 , and the CalabrHIV Study Group 1 Unità Operativa di Malattie Infettive, Azienda Ospedaliera Universitaria “Mater Domini”, Università “Magna Graecia” Catanzaro, Italy 2 Unità Operativa di Malattie Infettive, Azienda Ospedaliera Cosenza, Italy 3 Unità Operativa di Malattie Infettive, Azienda Ospedaliera “Bianchi Melacrino Morelli” Reggio Calabria, Italy 4 Unità Operativa di Malattie Infettive, Ospedale “Pugliese” Catanzaro, Italy 5 Unità Operativa di Malattie Infettive, Presidio Ospedaliero Lamezia Terme, Italy 6 Unità Operativa di Malattie Infettive, Ospedale “Jazzolino” Vibo Valentia, Italy 7 Unità Operativa di Malattie Infettive, Ospedale Crotone, Italy
Introduction and Aims HIV infected patients suffer from premature aging, putting them at risk of non-infectious co-morbidities at younger ages than the general population. Aim of this study is to evaluate for the first time prevalence of non-infectious co-morbidities and of multi-morbidity in HIV/HCV co-infected patients with respect to HIV mono-infected ones. Materials and Methods The CalabrHIV observational cohort includes all HIV patients followed by infectious disease centers in the Calabria Region. Epidemiological, clinical and demographic characteristics were collected in a common database. Non-infectious co-morbidities were recorded: cardiovascular diseases, hypertension, diabetes, renal failure and bone fractures. Multi-morbidity was defined as ≥2 non infectious co-morbidities occurring in the same patient. Results 549 patients were selected (69% males, 37% >50 years). Main risk factors were sexual promiscuities (50%) and IVDU (34%). 34% patients were HIV/HCV co-infected, 7% HBsAg carriers and 2% had triple co-infections. Hypertension was most frequent (25% overall). Multi-morbidity was higher from 50 years of age (30% vs. 6%; p < 0.0001). HIV co-infected patients had more frequently AIDS (39% vs. 21%; p < 0.0001). A statistically significant difference in multi-morbidity percentage was observed in patients aged >50 years with HCV and/or HBV co-infection than in HIV monoinfected ones (70% vs. 50%; p = 0.0037) (Figure 1). This effect was not driven by the oldest subjects since an increasing significance was found with increase in age starting from 40 years (39.5% vs.
Abstracts / Digestive and Liver Disease 47S (2015) e43–e66
F-11 CLINICAL RELEVANCE OF NEXT GENERATION SEQUENCING ON BASELINE DETECTION OF MINORITY RESISTANCE ASSOCIATED VARIANTS IN HCV-1 PATIENTS TREATED WITH PROTEASE INHIBITORS D. Armenia 1 , L. Carioti 1 , V.C. Di Maio 1 , M.C. Bellocchi 1 , D. Di Paolo 2 , F. Guerrieri 3 , L. Calvo 4 , V. Cento 1 , M. Tontodonati 5 , V. Micheli 6 , F. De Leonardis 2 , M. Aragri 1 , E. Polilli 7 , A. Manunta 8 , C. Magni 6 , F.P. Antonucci 1 , F. De Luca 1 , C. Sarrecchia 9 , A. Bertoli 1 , I. Lenci 2 , S. Francioso 2 , M.M. Santoro 1 , J. Vecchiet 5 , S. Marenco 10 , A. Picciotto 10 , L. Nosotti 11 , F. Morisco 12 , S. Bruno 13 , M. Puoti 14 , S. Babudieri 8 , M.S. Mura 8 , M. Andreoni 9 , G. Rizzardini 6 , G. Parruti 7 , M. Levrero 4 , M. Angelico 2 , C.F. Perno 1 , F. Ceccherini-Silberstein 1 1 Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy 2 Hepatology Unit, University Hospital of Rome “Tor Vergata”, Rome, Italy 3 Center for Life Nano Science, CNLS@SAPIENZA, IT 4 La Sapienza” University, Rome, Italy 5 Infectious Disease Clinic, Chieti, Italy 6 Hospital Sacco of Milan, Milan, Italy 7 Infectious Disease Unit, Pescara General Hospital, Pescara, Italy 8 Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy 9 Infectious Disease, University Hospital of Rome “Tor Vergata”, Rome, Italy 10 S. Martino University Hospital, Genoa, Italy 11 Hepatology Unit, National Institute of Health, Migration and Poverty, Rome, Italy 12 University “Federico II”, Naples, Italy 13 Internal Medicine, Gastroenterology and Hepatology, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy 14 Hospital Niguarda Ca’Granda, Milan, Italy
Background and Aims: This study aims to evaluate the clinical relevance of next-generation-sequencing on the baseline detection of minority resistance-associated-variants (RAVs) in chronic HCV-1 infected patients treated with telaprevir/ boceprevir + pegIFN/ribavirin. Methods: NS3-protease sequences of 25 selected patients (18 virological-failures and 7 responders) treated with telaprevir (N = 20) or boceprevir (N = 5) + pegIFN/ribavirin were analyzed. Detection of NS3-RAVs (V36ALM/T54AS/V55A/Q80 K/R155KT/ A156STV/V170A) was performed by Sanger-sequencing, 454junior-pyrosequencing (UDPS) and MiSeq-illumina (MiSeq). UDPS sequences were analyzed by a home-made-pipeline (>3,000 sequences/patient; cut-off > 0.1%); Miseq sequences were analyzed by VirVarSeq (>40,000 sequences/patient; cut-off ≥ 0.3%). Results: At baseline, 5/25 patients (20%) presented NS3-RAVs by Sanger, UDPS and MiSeq (Q80K = 3; T54S = 1; V36L + Q80K = 1, prevalence >98%). Of them, 4 patients experienced virologicalfailure and 1 (with Q80 K) achieved sustained-virological-response (SVR). Additional baseline minority-RAVs (Q80 K/V170A) were found by both UDPS and MiSeq in 2 patients, all with prevalence < 2.6%. However, their presence was not directly associated with virological-failure. Indeed, 1 previous-null-responder with
baseline minority Q80 K failed telaprevir-triple-therapy with different RAVs (V36AM + R155K + T156ST). The other patient, previous partial-responder, with baseline minority V170A achieved SVR. By using MiSeq, analyzing a larger number of sequences (median[IQR]:843,492[342,499-1,006,108]), a high number of NS3RAVs (N = 43,cut-off ≥0.3%) were detected in 19/25 patients (76%). In particular, V55A was the most prevalent RAV detected (52%), followed by V36A (36%), Q80 K (28%), and T54A (8%). The presence of these mutations at baseline was similar between responders and virological-failures. Interestingly, a unique HCV-1a infected patient previous-non-responder with 10 baseline minorityRAVs (V36A:0.41%; T54S:0.33%; V55A:0.47%, Q80 K:0.36%; R155 K:0.55%; R155 T:0.59%; A156S:1.19%; A156 T:0.64%; A156 V:0.50%, V170A:0.57%, with a median[IQR] mutational-load of 19,567[15,870-21,987] IU/ml) failed telaprevir-triple-therapy, with A156 T (week-2) and later with V36M + R155 K (week-10). Conclusions: Both UDPS and MiSeq detected baseline RAVs at very low frequency. However, these variants were not necessarily detected at virological-failure. Further investigations are needed to clarify the clinical relevance of minority RAVs at frequency below 1%. http://dx.doi.org/10.1016/j.dld.2015.01.105 F-12 CHRONIC INTERMITTENT HYPOXIA IS ASSOCIATED WITH LIVER DAMAGE AND ATHEROSCLEROSIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE S. Petta 1 , O. Marrone 2 , D. Torres 3 , M. Buttacavoli 4 , C. Cammà 1 , V. Di Marco 1 , A. Licata 1 , A. Lo Bue 2 , G. Parrinello 3 , A. Pinto 3 , A. Selvaggio 2 , A. Tuttolomondo 3 , A. Craxì 1 , M. Bonsignore 4 1 Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy 2 National Research Council, Institute of Biomedicine and Molecular Immunology, Palermo, Italy 3 Sezione di Medicina Interna, DiBiMIS,University of Palermo, Palermo, Italy 4 Sezione di Pneumologia, DiBiMIS,University of Palermo, Palermo, Italy
Background: Obstructive sleep apnea syndrome(OSAS) has been reported as a new risk factor for metabolic disturbances, including cardiovascular alterations. Growing data are also available among bariatric nonalcoholic fatty liver disease(NAFLD) patients on the impact of obstructive sleep apnea syndrome OSAS on liver damage in NAFLD. We assessed whether OSAS is associated with severity of liver fibrosis and carotid atherosclerosis in NAFLD patients without morbid obesity. Methods: 126 consecutive biopsy-proven(Kleiner score) NAFLD patients assessed for anthropometric, biochemical, and metabolic features underwent ultrasonographic carotid assessment and STOP BANG questionnaire for estimate of low or high OSAS risk. A carotid plaque was defined as a focal thickening > 1.3 mm at the level of either common and internal carotid arteries or bifurcations. 50 patients accepted to perform nocturnal cardiorespiratory polygraphy, and OSAS was defined if the as an apnea/hypopnea index AHI index was≥5. Results: The prevalence of high OSAS risk was similar in patients without and with polygraphy(76% vs 68%,p = 0.17). Among these last subjects who underwent polygraphy 50% had OSAS. The prevalence of an OSAS was significantly higher in patients with, than in
Abstracts / Digestive and Liver Disease 47S (2015) e43–e66
those without, F2-F4 fibrosis compared to those without(72% vs 44%, respectively; p = 0.04). After correction for confounders, significant fibrosis was associated with S02 mean levels≤95% mean oxyhemoglobin saturation(SaO2) levels < 95%(OR 3.21,95%C.I. 1.027.34;p = 0.04). Similarly, the prevalence of OSAS was slightly higher in patients with, than in those without, carotid plaques compared to(64% vs 40%;p = 0.08). After correction for confounders, the association between carotid plaques were associated with T90(time spent with SaO2 < 90%) >1% was maintained(OR 6.30,95%C.I.1.0212.3;p = 0.01). Conclusions: In NAFLD patients without morbid obesity OSAS was highly prevalent and indexes of oxygen saturation were independent indicators of the severity of liver fibrosis and of carotid atherosclerosis risk. These data, if further validated, could suggest to look at for OSAS in all NAFLD patients, considering OSAS as a potential additional therapeutic target for NAFLD. http://dx.doi.org/10.1016/j.dld.2015.01.106 F-13 IFNL4 POLYMORPHISMS PREDICT SUSTAINED RESPONSE AND HBSAG CLEARANCE IN INTERFERON TREATED HBEAG NEGATIVE CHRONIC HEPATITIS B PATIENTS E. Galmozzi 1 , P. Lampertico 1 , F. Facchetti 1 , F. Invernizzi 1 , G. Mangia 1 , M. Vigano 2 , R. Soffredini 1 , M. Colombo 1 1
Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 2 Liver Unit, Ospedale San Giuseppe, University of Milan, Milan, Italy Introduction and Aim The recently identified interferon lambda 4 (IFNL4) gene harbors the dinucleotide variant rs368234815-TT/G, a genetic marker of outcome to IFN-based therapy of HCV infection. The IFN-4 protein, which can be generated only by carriers of the rs368234815-G allele, is thought to counteract IFN responsiveness by inducing a weak expression of interferon-stimulated genes. Three nonsynonymous variants of the IFNL4 gene (rs73555604, rs142981501 and rs117648444) could affect the IFN-4 protein. We aimed to explore whether IFNL4 polymorphisms impact on response to IFN-based treatment in the setting of chronic hepatitis B (CHB). Materials and Methods IFNL4 gene was sequenced by Sanger method on genomic DNA extracted from whole blood of 126 HBeAg-negative CHB patients treated with either standard or pegylated-IFN-␣ and followed-up for 11 years (range 1-17) posttreatment. Results Sustained response rates to IFN were not significantly different between the 62 carriers of the rs368234815TT/TT (IFN-4 eliminating) genotype and the 64 carriers of the rs368234815-G (IFN-4 generating) allele (31% vs 17%, p = 0.079). Since the only nonsynonymous variant identified in our cohort, the Pro70Ser rs117648444-C/T polymorphism, was exclusively associated with carriers of the IFN-4 generating allele, these 64 patients were stratified into rs117648444-CC (IFNl-4 wild-type, n = 45) and rs117648444-CT/TT (IFNl-4 mutated, n = 19) genotypes. Sustained responses among IFN-4 eliminating (rs368234815-TT/TT) and IFN-4 mutated (rs117648444-CT/TT) genotypes (n = 81) were significantly higher than those in the 45 IFN-4 wild-type subjects (33.3% vs 9%, OR = 4.8, 95%CI 1.6-15.0, p = 0.006). Yet, in the multivariate analysis the combination of IFN-4 eliminating and IFN-4 mutated genotypes independently predict both sustained response to interferon (OR = 5.33, 95%CI 1.7-16.8, p = 0.004) and off treatment
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HBsAg clearance (HR = 4.3, 95%CI 1.5-12.3, p = 0.007). Pretreatment serum HBV-DNA was the only other independent predictor of HBsAg loss (HR = 0.61, 95%CI 0.43-0.87, p = 0.007). Conclusions IFNL4 polymorphisms independently predict sustained response to interferon and off treatment HBsAg clearance in HBeAg negative CHB patients. http://dx.doi.org/10.1016/j.dld.2015.01.107 F-14 NON-INFECTIOUS CO-MORBIDITIES IN HIV PATIENTS CO-INFECTED WITH HEPATITIS VIRUSES: AN ANALYSIS FROM THE CALABRHIV STUDY GROUP M.C. Postorino 1 , F. Luciani 2 , C. Mangano 3 , M.S. Carpentieri 3 , P. Scerbo 4 , A. Priamo 4 , G. Berardelli 5 , R. Marino 6 , A. Vallone 6 , N. Serrao 7 , V. Pisani 1 , C. Costa 1 , A. Terremoto 2 , G. Foti 3 , L. Cosco 4 , M. Calderazzo 5 , D. Corigliano 5 , P. Scordo 1 , C. Torti 1 , and the CalabrHIV Study Group 1 Unità Operativa di Malattie Infettive, Azienda Ospedaliera Universitaria “Mater Domini”, Università “Magna Graecia” Catanzaro, Italy 2 Unità Operativa di Malattie Infettive, Azienda Ospedaliera Cosenza, Italy 3 Unità Operativa di Malattie Infettive, Azienda Ospedaliera “Bianchi Melacrino Morelli” Reggio Calabria, Italy 4 Unità Operativa di Malattie Infettive, Ospedale “Pugliese” Catanzaro, Italy 5 Unità Operativa di Malattie Infettive, Presidio Ospedaliero Lamezia Terme, Italy 6 Unità Operativa di Malattie Infettive, Ospedale “Jazzolino” Vibo Valentia, Italy 7 Unità Operativa di Malattie Infettive, Ospedale Crotone, Italy
Introduction and Aims HIV infected patients suffer from premature aging, putting them at risk of non-infectious co-morbidities at younger ages than the general population. Aim of this study is to evaluate for the first time prevalence of non-infectious co-morbidities and of multi-morbidity in HIV/HCV co-infected patients with respect to HIV mono-infected ones. Materials and Methods The CalabrHIV observational cohort includes all HIV patients followed by infectious disease centers in the Calabria Region. Epidemiological, clinical and demographic characteristics were collected in a common database. Non-infectious co-morbidities were recorded: cardiovascular diseases, hypertension, diabetes, renal failure and bone fractures. Multi-morbidity was defined as ≥2 non infectious co-morbidities occurring in the same patient. Results 549 patients were selected (69% males, 37% >50 years). Main risk factors were sexual promiscuities (50%) and IVDU (34%). 34% patients were HIV/HCV co-infected, 7% HBsAg carriers and 2% had triple co-infections. Hypertension was most frequent (25% overall). Multi-morbidity was higher from 50 years of age (30% vs. 6%; p < 0.0001). HIV co-infected patients had more frequently AIDS (39% vs. 21%; p < 0.0001). A statistically significant difference in multi-morbidity percentage was observed in patients aged >50 years with HCV and/or HBV co-infection than in HIV monoinfected ones (70% vs. 50%; p = 0.0037) (Figure 1). This effect was not driven by the oldest subjects since an increasing significance was found with increase in age starting from 40 years (39.5% vs.