CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

544 “FIB-4 FIRST” STRATEGY IN A NAFLD PATHWAY ASSESSMENT FOR HIV MONOINFECTED PATIENTS Adriana Cervo 1 , Thomas Krahn 2 , Jovana Milic 3 , Sahar Saeed 2 , Bertrand Lebouché 2 , Marina Klein 2 , Philip Wong 2 , Marc Deschenes 2 , Peter Ghali 2 , Antonio Cascio 1 , Giovanni Mazzola 1 , Giovanni Guaraldi 3 , Giada Sebastiani 2 1 University Hospital of Palermo, Palerno, Italy, 2 McGill University Health Centre, Glen site, Montreal, QC, Canada, 3 University of Modena and Reggio Emilia, Modena, Italy Background: Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease in people living with HIV (PLWH). Even if transient elastography (TE) is a feasible and effective option to assess both NAFLD and fibrosis, it is not largely accessible. Fibrosis-4 (FIB-4) index at the threshold of 1.3 is used to exclude fibrosis in patients at risk for NAFLD from the general population. FIB-4 could be used to triage PLWH in need for further evaluation for NAFLD and associated liver fibrosis. The aims of this study were: i) to estimate the proportion of TE examinations which would be spared using a FIB-4 first strategy in PLWH; ii) to determine prevalence and associated cofactors of discordance (false negativity) between TE and FIB-4 in patients classified as low-risk fibrosis category by FIB-4. Methods: 1607 HIV mono-infected patients from three cohorts (LIVEHIV in Montreal, LHIVPA in Palermo, MHMC in Modena) were included if they fulfilled the following criteria: available TE and FIB-4 within 3 months; absence of significant alcohol intake and of coinfection with hepatitis B or C. NAFLD was defined as a controlled attenuation parameter (CAP) ≥ 248 dB/m. Significant fibrosis and cirrhosis were defined as liver stiffness measurement ≥ 7.1 and ≥ 13 kPa, respectively. Failure of TE examination was defined as IQR value >30%. A FIB-4 threshold of 1.3 was used to categorize patients as low or high-risk for fibrosis. Multivariable logistic regression analysis was used to identify cofactors associated with discordance between TE and FIB-4 in low-risk category. Results: Prevalence of NAFLD and liver fibrosis was 37% and 15%, respectively. 1022 patients (64%) were stratified as low risk: 108 (11%) had significant liver fibrosis by TE (of whom 78 patients had NAFLD and 13 patients had cirrhosis) (see Figure). After adjusting for sex, CD4 nadir, viral load, time to HIV diagnosis and diabetes, BMI ≥ 25kg/cm 2 (Odds Ratio [OR] 3.66, 95% CI: 2.29-5.84) and low HDL cholesterol (OR 1.72, 95% CI: 1.06-2.78) were independently associated with discordance between TE and FIB-4 in patients with FIB-4 <1.3. Conclusion: A FIB-4 first risk-stratification model could save more than 50% of TE examinations, helping resource optimization in HIV clinics. Patients stratified as low risk by FIB-4 should be considered for referral for TE examination in case of multiple risk factors for NAFLD, in particular overweight and low HDL cholesterol.

corresponding to moderate to severe steatosis. Concentrations of tryptophan metabolites in serumwere measured using liquid chromatography-tandem mass spectrometry. Information on smoking and physical activity was collected through questionnaires, and anthropometry was performed by trained medical professionals. We performed multiple linear regression modelling of log-transformed biomarker levels adjusted for age, sex, smoking status, waist- to-hip ratio and physical activity. Furthermore, we explored if IFN-γ mediated the effects of steatosis on tryptophan catabolism. Results: Among 799 PWH with both CT liver scan and measured kynurenines, steatosis was present in 61 (7.6%) (Table). KTR was 27.2 [95% Confidence Interval (CI): 25.1; 29.4] (nmol/µmol) among those with steatosis and 25.3 [95%CI: 24.8; 25.8] in those without steatosis, p=.046. Quinolinic acid concentrations were higher among those with steatosis compared to those without (466nM [95%CI: 425; 512] vs. 384nM [95%CI: 375; 394], p<.001). In adjusted analyses, steatosis was independently associated with 14% [95%CI: 4; 25] higher concentration of quinolinic acid, p=.005. After additional adjustment for IFN-γ, steatosis remained associated with 12% [95%CI: 3; 21] higher concentration of quinolinic acid. Kynurenine-to-tryptophan ratio was not associated with steatosis in adjusted analyses, p=.82 Conclusion: Serum levels of quinolinic acid were significantly higher among PWH with steatosis as defined by CT compared to PWH without steatosis, and this was not mediated by IFN-γ. There was no difference in kynurenine-to-tryptophan ratio. As quinolinic acid may impose oxidative stress, our findings suggest pro- inflammatory changes in the kynurenine pathway of tryptophan metabolism accompany steatosis in the context of HIV infection. However, the specific pathoaetiologic mechanisms underlying these changes should be explored in translational studies.

Poster Abstracts

546 IL-18 IS ASSOCIATED WITH HEPATOSTEATOSIS AND HIGHER LIVER ENZYMES IN PEOPLE WITH HIV Jae H. Sim 1 , Julia B. Sherman 2 , Kathleen V. Fitch 1 , Sara E. Looby 1 , Jake A. Robinson 3 , Michael Lu 1 , Steven K. Grinspoon 1 , Tricia H. Burdo 3 , Janet Lo 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 University of Massachusetts, Worcester, MA, USA, 3 Temple University, Philadelphia, PA, USA Background: People with HIV (PWH) are at increased risk of development of nonalcoholic fatty liver disease (NAFLD). In addition to insulin resistance and obesity, chronic inflammation is important in the pathogenesis of NAFLD. IL-18, a member of the pro-inflammatory IL-1 family, is regulated by inflammasomes in response to pathogens and danger signals. IL-18 is elevated in PWH and has been implicated in inflammation associated with obesity and NAFLD in people without HIV. We hypothesized that IL-18 may play a role in NAFLD progression in PWH. Methods: IL-18 was measured by ELISA (R&D) in an observational cohort of PWH and matched uninfected controls in the Boston area. Participants with known hepatitis C and excessive alcohol use were excluded. Liver lipid content was assessed by liver/spleen CT attenuation ratio (an estimate of hepatosteatosis in which a lower ratio indicates higher lipid content). IL-18 was log transformed to approximate a normal distribution. Results: A total of 134 PWH and 59 HIV-uninfected controls were included in the current analysis. PWH had higher log 10 IL-18 (2.40 ±0.19 [mean ±SD] vs 2.29 ±0.22, p=0.002), AST (33.3 ±12.9 vs 26.6 ±14.0 U/dL, p=0.01), and ALT (33.4

545 TRYPTOPHAN CATABOLISM IS ALTERED AMONG PERSONS WITH HIV WHO HAVE STEATOSIS Andreas D. Knudsen 1 , Marco Gelpi 1 , Søren Bjørnskov 1 , Ditte M. Kirkegaard- Klitbo 2 , Anne-Mette Lebech 2 , Henrik Ullum 1 , Klaus F. Kofoed 1 , Øivind Midttun 3 , Per M. Ueland 3 , Jens D. Lundgren 4 , Susanne D. Nielsen 1 1 Rigshospitalet, Copenhagen, Denmark, 2 Hvidovre Hospital, Hvidovre, Denmark, 3 University of Bergen, Bergen, Norway, 4 CHIP, Department of Infectious Diseases, Copenhagen, Denmark Background: Tryptophan catabolism as measured by the kynurenine-to- tryptophan ratio and concentrations of tryptophan metabolites are altered in persons with HIV (PWH). We aimed to explore if steatosis was associated with kynurenine-to-tryptophan ratio and quinolinic acid in PWH. Methods: PWH were recruited from the Copenhagen comorbidity in HIV

infection (COCOMO) study. We used an unenhanced CT liver scan to measure liver attenuation and defined steatosis as a liver attenuation ≤ 48 Hounsfield Units

CROI 2020 195