CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

HCV with and without HIV coinfection are lacking. Therefore, we compared the changes in Child-Pugh-Turcotte (CPT) and MELD scores between the start of treatment with DAA without IFN and SVR12 in patients with cirrhosis due to HCV with and without HIV coinfection. Methods: Individuals included in the HEPAVIR (NCT02057003), including HIV/HCV-coinfected patients, and GEHEP-MONO (NCT02333292), recruiting HCV-monoinfected patients, cohorts were selected if they met: 1) Cirrhosis; 2) SVR12 to IFN-free AAD. Changes in CPT and MELD indexes between the date of initiation of treatment (BL) and SVR12 in groups with [HIV (+)] and without HIV infection [HIV(-)] were compared. Results: 309 patients, 195 (63%) of them HIV(+), were included in this analysis. The proportion of patients with CPT> 5 HIV(-) vs. HIV(+) was: BL, 32 (28%) vs. 72 (37%) (p = 0.112) and SVR12, 19 (17%) vs. 47 (24%) (p = 0.124). Among patients with CPT> 5, CPT decreased in 24 (75%) and increased in 3 (9.4%) HIV(-) (BL vs. SVR12, p <0.001), and decreased in 47 (65%) and increased 5 (6.9%) HIV(+) (BL vs. SVR12, p <0.001). The median (Q1-Q3) BL MELD was 7 (6-9) for HIV(-) and 8 (6-10) for HIV(+) (p = 0.003). At the time of the SVR12, the median MELD (Q1-Q3) was 7 (6-9) for HIV(-) and 8 (6-10) for HIV(+) (p = 0.082). In patients with MELD> 6, MELD decreased in 36/70 (51%) and increased in 19/70 (27%) HIV(-) (BL vs. SVR12, p = 0.059), and decreased in 81/143 (57%) and increased in 40/143 (28%) HIV(+) (BL vs. SVR12, p <0.001). The frequency of CPT≥1 and/or MELD≥2 points increase between BL and SVR12 was 18 (16%) HIV(-) and 26 (14%) in HIV(+) (87%) (p = 0.545). After multivariate analysis (adjusted by liver stiffness, albumin, bilirubin, creatinine and INR) HIV was not associated with CPT≥1 and/or MELD≥2 points increase (adjusted OR 1,04, 95% confidence interval: 0,45-2,42; p=0,929). Conclusion: Although liver function of HIV(+) patients with cirrhosis due to HCV is worse than that of HIV(-) individuals at the start of DAA therapy, at SVR12 both groups show improvements in CPT and MELD. The frequency of liver function worsening after responding to DAA is similar in HIV(+) and HIV(-). 537 LIVER MICRORNA HSA-MIR-125A-5P MAY EXERT AN ONCOSUPPRESSOR EFFECT ON HCC Lorenzo Onorato 1 , Giorgio de Stefano 2 , Valentina Lodice 2 , Nunzia Farella 2 , Nicoletta Potenza 3 , Evangelista Sagnelli 1 , Aniello Russo 3 , Carmine Minichini 1 , Mario Starace 1 , Nicola Coppola 1 1 Second Univ of Naples, Naples, Italy, 2 AORN dei Colli, PO Cotugno, Naples, Italy, 3 Second Univ of Naples, Caserta, Italy Background: MicroRNAs are small non-coding RNAs that modulate gene expression at post-transcriptional level, playing a crucial role in cell differentiation and development. Human miR-125a-5p has been shown to play an anti-proliferative activity toward several cancer cell lines and to be downregulated in some tumors. We aimed to evaluate the hsa- miR-125a-5p concentration and the expression levels of 4 of its validated oncogenic targets in neoplastic and in non-neoplastic liver tissue of patients with HCC. Methods: All consecutive patients who underwent a diagnostic liver biopsy for HCC at one of two participating Liver Units from June 2013 to May 2014 were enrolled. For each patient, real-time PCR was used to quantify miR-125a-5p and its targeted transcripts in relation to RNU6B and GAPDH, respectively, in HCC and non-HCC liver tissue. Results: 55 patients were included in the study; the mean age was 70.3±6.0 years and 58.1% of patients were males. The etiologic agent was HCV in 41 patients, HBV in 10 and 4 had NASH-related cirrhosis (Child-Pugh class A in 89.1% of cases and classes-B/C in 10.9%). According to the Barcelona Clinic Liver Cancer (BCLC) class, 47 (85.4%) had class A, 5 (9.1%) class B and 3 (5.5%) class C. Lower levels of hsa-miR- 125a-5p were observed in HCC tissue than in non-HCC liver tissues (M±SD 4.08±2.87 vs. 8.25±4.53 A.U., p<0.00001). This difference was highly significant to statistical analysis in the 41 HCV-patients, 3.75±2.8 vs. 7.97±4.85 AU (p<0.00001) and still significant although at a lower level in the 10 HBsAg positive patients, 5.47±3.13, vs. 8.94±3.46AU (p=0.036), and in the 4 patients with NASH-related cirrhosis, 4.65±2.84 vs. 10.9±1.16 AU (p=0.015) (Figure 1). When patients were stratified according to the epidemiological and clinical characteristics of HCC, no difference was observed between the mean fold-regulation of the miRNA in HCC vs. non-HCC tissue. The analysis of the expression patterns of four validated targets showed an up-regulation of MMP11, SIRT7 and c-Raf, with mean fold regulation values of 3, 2.1 and 1.7, respectively. Conclusion: These data suggest an oncosuppressor effect of microRNA hsa-miR-125a-5p on HCV, HBV and NASH-related HCC; this effect could be exerted through the regulation of its oncogenic targets MMP11, SIRT7 and c-Raf , an observation deserving further investigation.

Poster and Themed Discussion Abstracts

538 REAL-LIFE TREATMENT RATES FOR HEPATOCELLULAR CARCINOMA IN HIV-INFECTED PATIENTS Nicolás Merchante 1 , Francisco Rodríguez-Arrondo 2 , Esperanza Merino 3 , Boris Revollo 4 , Sofía Ibarra 5 , Miguel García-Deltoro 6 , Francisco Téllez 7 , Joseba Portu 8 , Alberto Romero- Palacios 9 , Juan A. Pineda 1 1 Hosp Univ de Valme, Sevilla, Spain, 2 Hosp Univ de Donostia, San Sebastián, Spain, 3 Hosp General Univ de Alicante, Alicante, Spain, 4 Hosp German Trias i Pujol, Badalona, Spain, 5 Hosp de Basurto, Basurto, Spain, 6 Hosp General de Valencia, Valencia, Spain, 7 Hosp de La Línea, La Línea de la Concepción, Spain, 8 Hosp de Txagorritxu, Vitoria, Spain, 9 Hosp de Puerto Real, Puerto Real, Spain Background: The incidence of hepatocellular carcinoma (HCC) in HIV-infected patients is increasing worldwide. It is not known if HIV-infected patients access effective therapy against HCC. Our aimwas to assess the proportion of HIV-infected patients with HCC that do not access recommended therapy according to HCC stage.

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