CROI 2018 Abstract eBook
Abstract eBook
Poster Abstracts
643 UNANTICIPATED INCREASES IN FATTY LIVER IN HIV NAFLD PATIENTS WITH EPLERENONE Chloe S. Chaudhury 1 , Julia Purdy 2 , Chia-Ying Liu 2 , Caryn G. Morse 2 , Takara L. Stanley 3 , David E. Kleiner 4 , Colleen Hadigan 1 1 NIAID, Bethesda, MD, USA, 2 NIH, Bethesda, MD, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 National Cancer Institute, Bethesda, MD, USA Background: Nonalcoholic fatty liver disease (NAFLD) is common in HIV, often seen in association with metabolic syndrome, however there are no approved therapies for NAFLD. Promising mouse models demonstrate the efficacy of mineralocorticoid receptor (MR) antagonists for attenuation of the effects of fatty liver disease, including marked reductions in fasting glucose, insulin, steatosis, and inflammation in mice fed a high-fat diet receiving an MR antagonist. Methods: The aim of this open-label proof-of-concept study was to determine the effect of the MR antagonist eplerenone on hepatic fat in 20 HIV+ patients with steatosis, defined as hepatic fat ≥ 5% by magnetic resonance spectroscopy (MRS). Five subjects received eplerenone (25 mg daily x 1 week followed by 50 mg daily x 23 weeks). Laboratory tests were done at each visit, and the primary endpoint, change in hepatic fat content, was determined by MRS at baseline and week 24. An additional MRS was performed 1-2 months after drug discontinuation. Results: We observed unexpected significant increases in hepatic fat at the week 24 (mean increase 13.2 ± 8.1%, p=0.02) (See Figure 1). There was a trend to return to baseline hepatic fat levels during the ‘washout’ (mean -9.6 ± 9.5%, p=0.08). In two participants with pre- and post-eplerenone liver biopsies, steatosis grade increased confirming the MRS observations. Surprisingly, the increases in steatosis were accompanied by a tendency for transaminase values to decrease (ALT mean change -14 ± 17 IU/L, p=0.14). There were no consistent improvements in HbA1c, fasting glucose, total cholesterol, triglycerides, or blood pressure. Initial rise in aldosterone was observed as expected, however, three subjects’ aldosterone levels returned to near baseline by week 24. Conclusion: The unexpected observation of increased hepatic steatosis with administration of eplerenone led to a pause in enrollment and early termination of the investigation. While limited due to the small number of participants and the open-label design, the present study provides compelling data to suggest that MR antagonism, at least with eplerenone, is not a reasonable approach to treat NAFLD in HIV or in the general population. Additional research is needed to determine the pathophysiologic mechanism behind these unanticipated observations.
La Fe, Valencia, Spain, 8 Hospital General de Valencia, Valencia, Spain, 9 Hospital Universitario Reina Sofia, Cordoba, Spain, 10 Hospital Regional Universitario de Málaga, Málaga, Spain, 11 Hospital Universitario de Puerto Real, Cadiz, Spain, 12 Hospital Universitario Virgen Macarena, Sevilla, Spain, 13 Hospital de Txagorritxu, Vitoria, Spain Background: Surveillance of hepatocellular carcinoma (HCC) by hepatic ultrasound (US) every 6 months is recommended in HIV-infected patients with cirrhosis. However, there are no specific studies addressing the performance of such strategy in this population. As it has been reported that HCC could have a more aggressive course in the HIV-infected patient, the effectiveness of this surveillance policy needs to be evaluated in this specific scenario. The objective of this study was to assess the proportion of HIV-infected patients diagnosed of HCC soon after a normal surveillance US. Methods: The GEHEP-002 multicentric cohort (ClinicalTrials.gov ID: NCT02785835) recruits HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. For this analysis, HCC cases diagnosed within an US screening programwere selected. Surveillance failure was defined as the diagnosis of an HCC within the first 3 months after a previous surveillance US not showing hepatic nodules. The characteristics of HCC cases after surveillance failure were compared with the remaining HCC cases diagnosed by screening. Results: 186 (54%) out of 341 HCC cases recruited in the GEHEP-002 have been diagnosed within an US screening program. Of them, 16 had a normal US in the preceding 3 months. Thus, the rate of HCC diagnosis after US surveillance failure was 8.6%. HCC was associated with HCV infection in these 16 cases. HCV genotype 3 infection was responsible for 5 (31%) out of the 16 cases after surveillance failure vs 43 (25%) among the remaining 180 cases diagnosed by screening (p=0.5). Two (12%) cases of those occurring after surveillance failure and 19 (11%) among the remaining cases were diagnosed after the consecution of SVR (p=0.7). There was a trend for a higher frequency of multicentric presentation [9 (60%) vs 74 (44%), p=0.2] and portal thrombosis [6 (37%) vs 40 (23%), p=0.2] among HCC cases after surveillance failure. Thus, 10 (62.5%) of themwere diagnosed at advanced stage (BCLC stage C or D) whereas this occurred in 76 (45%) of the remaining cases (p=0.1). Conclusion: A significant proportion of HIV-infected patients are diagnosed of HCC soon after a previous normal surveillance US. HCC cases after US surveillance failure tend to showmore advanced presentation at diagnosis. A HCC surveillance policy based on the performance of an US every 6 months might be insufficient in HIV-infected patients with cirrhosis. 645 HIV+ PERSONS WITH CIRRHOSIS RECEIVE INADEQUATE SCREENING FOR ESOPHAGEAL VARICES Chiara Saroli Palumbo , Amine Benmassaoud, Thomas Pembroke, Bertrand Lebouché, Philip Wong, Marc Deschenes, Marina Klein, Peter Ghali, Giada Sebastiani McGill University Health Centre, Glen site, Montreal, QC, Canada Background: HIV positive (HIV+) people are at increased risk of developing cirrhosis and its complications, including variceal hemorrhage. The Baveno VI consensus provides guidance as to which patients with cirrhosis should be screened for esophageal varices, and which can safely forego esophagogastroduodenoscopy (EGD), based on transient elastography (TE) and platelet values. We aimed to determine whether Baveno VI consensus guidelines are appropriately applied in HIV+ as compared to HIV negative (HIV-) individuals with liver disease. Methods: A prospective cohort study was conducted since 2015, which included HIV+ and HIV- persons who underwent TE as part of a routine screening program for liver disease. Liver cirrhosis was defined as TE measurement >13kPa. Baveno VI guidelines (TE measurement ≥20kPa and platelets ≤150,000) were applied to identify those at very low risk of having varices, and who could avoid screening with EGD. Multivariable logistic regression analysis was used to investigate independent cofactors associated with deviation from the Baveno VI guidelines. Diagnostic accuracy screening according to Baveno VI guidelines as compared to universal EGD was computed. Results: 725 HIV+ (mean age 49 years, 75.2%men; 35%with fatty liver, 21% HIV/HCV co-infected) and 785 HIV- patients (mean age 51 years, 59%men; 36% with fatty liver, 38%with HCV) were included. Prevalence of cirrhosis in the whole cohort was 19%. Overall, 78.8% HIV+ and 73.8% HIV- patients met the Baveno VI guidelines for not requiring screening EGD. In the remaining cases who required screening, EGD was performed in only 22.7% of HIV+ as compared to 87.4% of HIV- patients (p<0.001). Incidence of variceal bleeding was higher in
Poster Abstracts
644 FAILURE RATE OF ULTRASOUND SURVEILLANCE OF HEPATOCELLULAR CARCINOMA IN HIV+ PATIENTS Nicolás Merchante 1 , Esperanza Merino 2 , Francisco Rodríguez-Arrondo 3 , Boris Revollo 4 , Sofía Ibarra 5 , Maria J. Galindo 6 , Marta Montero 7 , Miguel García- Deltoro 8 , Antonio Rivero-Juárez 9 , Marcial Delgado-Fernández 10 , Francisco Téllez 11 , Maria J. Rios-Villegas 12 , Jose J. Portu 13 , Juan A. Pineda 1 1 Hospital Universitario de Valme, Seville, Spain, 2 Hospital General Universitario de Alicante, Alicante, Spain, 3 Hospital Donostia, San Sebastián, Spain, 4 Hospital Germans Trias i Pujol, Barcelona, Spain, 5 Hospital de Basurto, Basurto, Spain, 6 Hospital Clinic of Valencia, Valencia, Spain, 7 Hospital Universitario y Politecnico
CROI 2018 239
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