CROI 2016 Abstract eBook

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Poster Abstracts

606 Hepatitis C Genotype 6 is AssociatedWith Progression of Liver Fibrosis in HIV Patients Anchalee Avihingsanon 1 ; Suparat Khemnark 2 ;Tanakorn Apornpong 1 ; Sivaporn Kukanok 1 ;Vorapot Sapsirisavat 1 ; Salyavit Chittmittrapap 2 ; Stephen J. Kerr 1 ; SombatTreeprasertsuk 2 ; PisitTankijvanich 2 ; Kiat Ruxrungtham 1 ; for the HCV StudyTeam 1 HIV-NAT, Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand; 2 Chulalongkorn Univ, Bangkok, Thailand Background: Assessing liver fibrosis is critical for prioritizing candidates for HCV treatment in resource limited settings (RLS). We determined the rate of liver fibrosis progression and any factors that were associated with progression of fibrosis among untreated chronic hepatitis C patients with HIV (HIV/HCV) by using Liver stiffness measurement (LSM) by FibroScan. Methods: Untreated chronic HIV/HCV co-infected patients (detectable HCV RNA for >6 months) were prospectively enrolled between January 1, 2011 and June 30, 2015. LSM was measured at first LSM (baseline) and after >6 months of follow-up. Logistic regression was used to assess factors associated with progression of liver fibrosis, defined as LSM increasing by ≥1 stage or >3 KPa if stage was F4 at baseline. Advanced liver fibrosis was defined as LSM≥9.5 KPa (stages F3 or F4). Results: Totally 133 HIV/HCV cases (85%male, 58.7% IDU, 24.8%MSM) were enrolled. The median age was 40 years. All patients were taking HAART and had undetectable HIV RNA at baseline. HCV genotype (GT) distributions were 44 % GT3, 43% GT1 and 13% GT6. Median duration from baseline to last LSM was 2.1 (IQR 1.0-3.1) years. Median LSM at baseline was 8.6 (IQR 6.1-14) KPa and 41% of patients met criteria for advanced liver fibrosis. At the follow-up visit, 48/55 (87%) of subjects with advanced fibrosis at baseline remained in stage F3-F4, and 22/78 (28%) of patients with non-advanced fibrosis at baseline had LSM indicating progression to F3-F4. Liver fibrosis progression of ≥1 stage was noted in 50/133 (38%) patients. In all patients, the median rate of fibrosis progression was 1.4 (IQR 0.4-4.4) KPa/year. Patients with advanced fibrosis at baseline had a higher degree of liver fibrosis progression [median=3.6 (IQR 1.4-6.5) KPa/year] than those with less advanced disease at baseline [median=1.0 (IQR 0.3-2.4) KPa/year]. In multivariate analysis, HCV genotype 6 (OR 4.02,95%CI=1.10-14.76,p=0.047 versus GT1) and duration of HCV infection in years (OR 1.06,95%CI=1.00-1.11,p=0.028) were significantly associated with progression of liver fibrosis. The odds of liver fibrosis progression in patients with genotype 3 was not significantly different to patients with GT1 (OR 1.38,95%CI=0.52-3.18, p=0.28). Conclusions: Patients with untreated HIV/HCV genotype 6 had a greater rate of fibrosis progression than genotypes 1 and 3, and should be prioritized for HCV treatment where resources are constrained. 607 Impact of Occult HBV Infection in HCC Presentation in HCV-Related Cirrhosis Nicola Coppola 1 ;Valentina Iodice 2 ; Mario Starace 1 ; Carmine Minichini 1 ; Nunzia Farella 2 ; Lorenzo Onorato 1 ; Giulia Liorre 2 ; Evangelista Sagnelli 1 ; Giorgio De Stefano 2 1 Second Univ of Naples, Naples, Italy; 2 AORN dei Colli, P.O. Cotugno, Naples, Italy Background: The role of the occult HBV infection (OBI) as an additional risk factor for hepatocellular carcinoma (HCC) has not been fully investigated. The aim of this study was t o evaluate the virological and clinical characteristics of OBI (HBV DNA in liver tissue in HBsAg negative patients) in HBsAg negative subjects with HCC Methods: 68 consecutive HBsAg negative patients with HCC were enrolled at two centers from June 2013 to December 2014: 57.3%males; mean age 70.2±6.24 years; 58 (85.3%) with HCV-related cirrhosis and 10 (14.7%) with non-alcoholic fatty liver diseases-related cirrhosis; 85.3%with a Child-A stage cirrhosis; 69.1% at first diagnosis of HCC, 2.9%with portal thrombosis; 89.7%with a BCLC stage-A HCC. For each patient HBV DNA was sought by PCR in plasma, HCC-liver tissue and non-HCC-liver tissue, using sets of primers for core, surface and x regions of HBV genome. Occult HBV infection was defined by the presence of HBV DNA in at least two different PCRs Results: OBI was identified in 3 patients (4.4%)both in HCC-liver tissue and non-HCC-liver tissue and in 10 (14.7%) only in HCC-liver tissue; no patient showed OBI in plasma. OBI was detected more frequently in the 11 anti-HBs negative/anti-HBc positive and in the 17 anti-HBs/anti-HBc positive than in the 40 anti-HBs/anti-HBc negative patients (54.5%, 29.4% and 5%, respectively; p<0.0005). The analysis of pre-S1, pre-S2 and S regions showed the presence of aa substitutions in S region (F19L, S59F, T131I, Q129H), deletions in position 4,8 an 17 in pre-S1region and aa substitution in pre-S2 region (P41H). The demographic, biochemical and clinical (unifocal or multifocal HCC, diameter of HCC, HCC localization) were similar in the 13 patients with OBI and in the 55 without. However, the 13 patients with OBI than the 55 without showed a more severe cirrhosis (Child B or C stage: 53.9% vs. 5.5%, p<0.0001) and more advanced HCC (BCLC B or C stage: 46.1% vs. 1.8%, p<0.0001) Conclusions: OBI was found in 19.1% of the HBsAg negative patients with HCC, more frequently in anti-HBc positive patients. The OBI seems to have a clinical impact in HCC presentation and HBsAg mutations correlated with HCC progression and failure in HBsAg detection 608 CB2-63 RR Variant Is AssociatedWith Immune-Mediated Disorders in HCV Patients Nicola Coppola ; Rosa Zampino; Giulia Bellini; Maria Stanzione; Nicolina Capoluongo; Margherita Macera; Luigi E. Adinolfi; Emanuele Miraglia Del Giudice; Evangelista Sagnelli; Francesca Rossi Second Univ of Naples, Naples, Italy Background: Patients with HCV chronic infection frequently show immune-mediated disorders (IMDs). The Cannabinoid (CB) receptor 2, predominantly expressed in the immune cells, plays an important role on the function of the immune system. In particular, the CB2-63 variants (rs35761398) affects the ability of the CB2 receptor to exert its inhibitory function on T lymphocyte. The aim is to evaluate whether CB2 variants are associated with the presence of IMDs in patients with chronic HCV infection Methods: Considering that nearly 30% of anti-HCV positive patients are affected by IMDs, we planned a 12-month recruitment period for treatment-naïve anti-HCV positive patients with signs of IMD and a 4-month period for treatment-naïve anti-HCV patients lacking these signs. The enrollment stared in September 2013 and at the end of the recruitment periods 168 patients have been selected, 81 anti-HCV/HCV-RNA positive with signs of IMDs and 87 anti-HCV/HCV-RNA positive with no sign of IMDs. The presence of IMDs was defined by at least one of the following conditions: ANA positivity (titers ≥1:160) observed in 22 (27.2%) cases , SMA positivity (titers ≥1:160) in 3 (3.7%), a cryocrite >2% in 24 (29.6%), history or active autoimmune thyroiditis in 25 (30.9%), psoriasis in 4 (4.9%), B-cells non-Hodgkin lymphoma in 2 (2.5%) and autoimmune hemolytic anemia in 1 (1.2%) case; no patient showed signs of lichen planus nor Syogren syndrome. All patients were screened for the CNR2 rs35761398 SNP by a TaqMan Assay Results: Compared with the 87 patients lacking IMDs, the 81 in the IMDs group more frequently were females (65% vs 45%, p=0.01), but not other significant difference was found in initial demographic, epidemiologic, serological, biochemical and virological data. In particular, the age (mean+SD: 53±14.1 vs. 52.9±13.4 years), ALT serum levels, HCV viral load and in distribution of HCV genotypes were similar in these two groups. Instead, the prevalence of the patients with the CB2-63 RR variant was significantly higher in patients in the IMD group than in those in the non-IMD group (49.4% vs 24.1%, p=0.001). A logistic regression analysis including the CB2-63 receptor (RR vs QR or QQ), age and sex, identified the CB2-63 RR as the only independent predictor of IMDs (p =0.005). Conclusions: the data suggest a significant previously unknown association between CB2-63 RR variant and IMDs in anti-HCV patients, an observation deserving further investigation on a larger series of patients to define its clinical value 609 Prevalence and Risk Factors of LowMuscle Mass in HIV/Viral Hepatitis Coinfection Charitha Gowda 1 ;ToddT. Brown 2 ; Charlene Compher 1 ; Kimberly A. Forde 1 ; Jay R. Kostman 3 ; Pamela A. Shaw 4 ; PhyllisTien 5 ;Vincent Lo Re 1 1 Univ of Pennsylvania, Philadelphia, PA, USA; 2 Johns Hopkins Univ, Baltimore, MD, USA; 3 John Bell Hlth Cntr, Philadelphia, PA, USA; 4 Univ of Pennsylvania, Phialdelphia, PA, USA; 5 Univ of California San Francisco, San Francisco, CA, USA Background: Lowmuscle mass (LMM) in HIV is associated with reduced survival and may be mediated by systemic inflammation. Coinfection with viral hepatitis may induce additional inflammation that can contribute to LMM. We determined the prevalence of LMM in HIV/viral hepatitis patients on antiretroviral therapy (ART) compared to ART-treated HIV-monoinfected, viral hepatitis-monoinfected, and uninfected persons, and identified risk factors for LMM in coinfected patients.

Poster Abstracts

245

CROI 2016